今日の臨床サポート

MRSA感染症

著者: 冲中敬二 国立がん研究センター東病院 総合内科

監修: 大曲貴夫 国立国際医療研究センター

著者校正/監修レビュー済:2020/01/31
参考ガイドライン:
  1. 米国感染症学会(IDSA):Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children(2011)
  1. 日本化学療法学会日本感染症学会:MRSA感染症の治療ガイドライン 改訂版2019
  1. 日本化学療法学会:抗菌薬TDMガイドライン改訂版(2016)
患者向け説明資料

概要・推奨   

  1. バンコマイシンは必ず血中濃度モニタリング(TDM)を行い、トラフを最低でも10~20mg/Lに、重症感染症なら15 mg/L以上に調節することが勧められる(推奨度1)。
  1. 肺炎治療開始前には喀痰の培養検査を実施すべきである(推奨度1)。
  1. MRSA肺炎の診断は非常に困難であるが、致死率の高い疾患であり見落とさないように注意すべきである(推奨度1)。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
冲中敬二 : 特に申告事項無し[2021年]
監修:大曲貴夫 : 特に申告事項無し[2021年]

改訂のポイント:
  1. MRSA感染症の治療ガイドライン 改訂版2019に基づき確認を行った。
  1. テジゾリドの記載を追記した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. メチシリン耐性黄色ブドウ球菌(MRSA)は、病院内感染症の代表的な起炎菌の1つであるが[1]、若年健常者の皮膚軟部組織感染症を中心に、市中発症のMRSA感染症も報告されている[2]
 
病院内関連MRSAと市中関連MRSAの違い

Panton-Valentine leucocidin:黄色ブドウ球菌の産生するトキシンの1つ。市中関連MRSA感染症、中でも壊死性肺炎との関連が指摘されているものの、議論のあるところである。

出典

img1:  Meticillin resistant Staphylococcus aureus in the hospital.
 
 BMJ. 2009 Feb 12;338:b364. Epub 2009 Feb・・・
 
  1. 傷ついた皮膚軟部組織や異物への感染、血液・血管内感染症にはしばしば関与するが、尿路感染症[3]や消化管感染症[4]の頻度は低く、各種培養検体から検出された場合には真の起炎菌かどうかの慎重な判断が必要である。
  1. 黄色ブドウ球菌による下気道感染症は診断が難しい感染症であるが、近年黄色ブドウ球菌やMRSAよる医療関連肺炎の頻度が増加しているとの報告もある[5]。致死率の高い感染症であり見落とさないように注意が必要である。喀痰からMRSAを検出したすべての症例がMRSA肺炎というわけではなく、真の起炎菌かどうか慎重に判断する必要がある。
  1. エンテロトキシンやToxic Shock Syndrome Toxin-1などの毒素を産生し、食中毒やToxic Shock症候群(TSS)などを引き起こす。
  1. 近年、分離される黄色ブドウ球菌株に占めるMRSAの割合は減少傾向である。
 
MRSAの分離患者数と分離率の変遷

グローバルのサーベイランスデータでは黄色ブドウ球菌血流感染症に占めるMRSAの割合は、2005~2008年をピークに減少傾向であることが示されている。
参考文献:
Diekema DJ, Pfaller MA, Shortridge D, Zervos M, Jones RN. Twenty-Year Trends in Antimicrobial Susceptibilities Among Staphylococcus aureus From the SENTRY Antimicrobial Surveillance Program. Open Forum Infect Dis. 2019 Mar 15;6(Suppl 1):S47-S53. doi: 10.1093/ofid/ofy270. eCollection 2019 Mar. Erratum in: Open
Forum Infect Dis. 2019 May 20;6(5):ofz202. Zervos, Marcos [corrected to Zervos,
Marcus]. PubMed PMID: 30895214; PubMed Central PMCID: PMC6419894.

 
  1. MRSA肺炎の診断は非常に困難である。市中発症のMRSA肺炎は医療関連よりも頻度が低いものの致死率の高い疾患であり見落とさないように注意すべきである(推奨度1)。
  1. まとめ:市中MRSA肺炎は診断が困難な疾患である。
  1. 説明:市中肺炎においてMRSAを想起させる因子として、先行するインフルエンザ感染症やインフルエンザ様疾患があり、約75%にこれらがみられる[6][7]。臨床的な特徴としては、急激に増悪し、組織侵襲性が強く、血痰、強い呼吸器症状や低血圧、複数の葉にまたがる空洞形成性のX線所見なども疑うきっかけとなる[8]。膿胸や肺膿瘍形成などの合併例も多く、外科的処置の必要性に関しても評価が必要となる[9]。入院した患者の81%にICU管理、62%に気管内挿管管理を必要とするなど重症例が多く、致死率が29%に至るとの報告もある[6]。血行播種に伴う肺炎もしばしば起こる。
  1. 結論:市中MRSA肺炎は頻度が低いが、予後の悪い重症感染症であり治療開始が遅れないよう注意が必要である。
問診・診察のポイント  
  1. MRSAの一般的な危険因子を確認する。

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文献 

著者: Alicia I Hidron, Jonathan R Edwards, Jean Patel, Teresa C Horan, Dawn M Sievert, Daniel A Pollock, Scott K Fridkin, National Healthcare Safety Network Team, Participating National Healthcare Safety Network Facilities
雑誌名: Infect Control Hosp Epidemiol. 2008 Nov;29(11):996-1011. doi: 10.1086/591861.
Abstract/Text OBJECTIVE: To describe the frequency of selected antimicrobial resistance patterns among pathogens causing device-associated and procedure-associated healthcare-associated infections (HAIs) reported by hospitals in the National Healthcare Safety Network (NHSN).
METHODS: Data are included on HAIs (ie, central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections) reported to the Patient Safety Component of the NHSN between January 2006 and October 2007. The results of antimicrobial susceptibility testing of up to 3 pathogenic isolates per HAI by a hospital were evaluated to define antimicrobial-resistance in the pathogenic isolates. The pooled mean proportions of pathogenic isolates interpreted as resistant to selected antimicrobial agents were calculated by type of HAI and overall. The incidence rates of specific device-associated infections were calculated for selected antimicrobial-resistant pathogens according to type of patient care area; the variability in the reported rates is described.
RESULTS: Overall, 463 hospitals reported 1 or more HAIs: 412 (89%) were general acute care hospitals, and 309 (67%) had 200-1,000 beds. There were 28,502 HAIs reported among 25,384 patients. The 10 most common pathogens (accounting for 84% of any HAIs) were coagulase-negative staphylococci (15%), Staphylococcus aureus (15%), Enterococcus species (12%), Candida species (11%), Escherichia coli (10%), Pseudomonas aeruginosa (8%), Klebsiella pneumoniae (6%), Enterobacter species (5%), Acinetobacter baumannii (3%), and Klebsiella oxytoca (2%). The pooled mean proportion of pathogenic isolates resistant to antimicrobial agents varied significantly across types of HAI for some pathogen-antimicrobial combinations. As many as 16% of all HAIs were associated with the following multidrug-resistant pathogens: methicillin-resistant S. aureus (8% of HAIs), vancomycin-resistant Enterococcus faecium (4%), carbapenem-resistant P. aeruginosa (2%), extended-spectrum cephalosporin-resistant K. pneumoniae (1%), extended-spectrum cephalosporin-resistant E. coli (0.5%), and carbapenem-resistant A. baumannii, K. pneumoniae, K. oxytoca, and E. coli (0.5%). Nationwide, the majority of units reported no HAIs due to these antimicrobial-resistant pathogens.

PMID 18947320  Infect Control Hosp Epidemiol. 2008 Nov;29(11):996-1011・・・
著者: Gregory J Moran, Anusha Krishnadasan, Rachel J Gorwitz, Gregory E Fosheim, Linda K McDougal, Roberta B Carey, David A Talan, EMERGEncy ID Net Study Group
雑誌名: N Engl J Med. 2006 Aug 17;355(7):666-74. doi: 10.1056/NEJMoa055356.
Abstract/Text BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized in infections among persons in the community without established risk factors for MRSA.
METHODS: We enrolled adult patients with acute, purulent skin and soft-tissue infections presenting to 11 university-affiliated emergency departments during the month of August 2004. Cultures were obtained, and clinical information was collected. Available S. aureus isolates were characterized by antimicrobial-susceptibility testing, pulsed-field gel electrophoresis, and detection of toxin genes. On MRSA isolates, we performed typing of the staphylococcal cassette chromosome mec (SCCmec), the genetic element that carries the mecA gene encoding methicillin resistance.
RESULTS: S. aureus was isolated from 320 of 422 patients with skin and soft-tissue infections (76 percent). The prevalence of MRSA was 59 percent overall and ranged from 15 to 74 percent. Pulsed-field type USA300 isolates accounted for 97 percent of MRSA isolates; 74 percent of these were a single strain (USA300-0114). SCCmec type IV and the Panton-Valentine leukocidin toxin gene were detected in 98 percent of MRSA isolates. Other toxin genes were detected rarely. Among the MRSA isolates, 95 percent were susceptible to clindamycin, 6 percent to erythromycin, 60 percent to fluoroquinolones, 100 percent to rifampin and trimethoprim-sulfamethoxazole, and 92 percent to tetracycline. Antibiotic therapy was not concordant with the results of susceptibility testing in 100 of 175 patients with MRSA infection who received antibiotics (57 percent). Among methicillin-susceptible S. aureus isolates, 31 percent were USA300 and 42 percent contained pvl genes.
CONCLUSIONS: MRSA is the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities. When antimicrobial therapy is indicated for the treatment of skin and soft-tissue infections, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage.

Copyright 2006 Massachusetts Medical Society.
PMID 16914702  N Engl J Med. 2006 Aug 17;355(7):666-74. doi: 10.1056/N・・・
著者: B Schiller, N Chiorazzi, B F Farber
雑誌名: Am J Med. 1998 Aug;105(2):164-6.
Abstract/Text
PMID 9727825  Am J Med. 1998 Aug;105(2):164-6.
著者: Lindsey M Weiner, Amy K Webb, Brandi Limbago, Margaret A Dudeck, Jean Patel, Alexander J Kallen, Jonathan R Edwards, Dawn M Sievert
雑誌名: Infect Control Hosp Epidemiol. 2016 Nov;37(11):1288-1301. doi: 10.1017/ice.2016.174. Epub 2016 Aug 30.
Abstract/Text OBJECTIVE To describe antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred in 2011-2014 and were reported to the Centers for Disease Control and Prevention's National Healthcare Safety Network. METHODS Data from central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonias, and surgical site infections were analyzed. These HAIs were reported from acute care hospitals, long-term acute care hospitals, and inpatient rehabilitation facilities. Pooled mean proportions of pathogens that tested resistant (or nonsusceptible) to selected antimicrobials were calculated by year and HAI type. RESULTS Overall, 4,515 hospitals reported that at least 1 HAI occurred in 2011-2014. There were 408,151 pathogens from 365,490 HAIs reported to the National Healthcare Safety Network, most of which were reported from acute care hospitals with greater than 200 beds. Fifteen pathogen groups accounted for 87% of reported pathogens; the most common included Escherichia coli (15%), Staphylococcus aureus (12%), Klebsiella species (8%), and coagulase-negative staphylococci (8%). In general, the proportion of isolates with common resistance phenotypes was higher among device-associated HAIs compared with surgical site infections. Although the percent resistance for most phenotypes was similar to earlier reports, an increase in the magnitude of the resistance percentages among E. coli pathogens was noted, especially related to fluoroquinolone resistance. CONCLUSION This report represents a national summary of antimicrobial resistance among select HAIs and phenotypes. The distribution of frequent pathogens and some resistance patterns appear to have changed from 2009-2010, highlighting the need for continual, careful monitoring of these data across the spectrum of HAI types. Infect Control Hosp Epidemiol 2016;1-14.

PMID 27573805  Infect Control Hosp Epidemiol. 2016 Nov;37(11):1288-130・・・
著者: Yves Gillet, Bertrand Issartel, Philippe Vanhems, Jean-Christophe Fournet, Gerard Lina, Michèle Bes, François Vandenesch, Yves Piémont, Nicole Brousse, Daniel Floret, Jerome Etienne
雑誌名: Lancet. 2002 Mar 2;359(9308):753-9. doi: 10.1016/S0140-6736(02)07877-7.
Abstract/Text BACKGROUND: Between 1986 and 1998, eight cases of community-acquired pneumonia due to Staphylococcus aureus strains carrying the gene for the Panton-Valentine leukocidin (PVL) were recorded in France, six of which were fatal. We aimed to assess the clinical features of these eight cases, and those of other cases identified prospectively, and to compare them with the characteristics of patients with pneumonia caused by PVL-negative strains.
METHODS: We compared eight retrospective and eight prospective cases of PVL-positive S aureus pneumonia with 36 cases of PVL-negative S aureus pneumonia. For all patients, we recorded age, length of hospital stay, risk factors for infection, signs and symptoms, laboratory findings, antibiotic treatment, and serial radiological findings.
FINDINGS: Median age was 14.8 years (IQR 5.4-24.0) for the PVL-positive patients and 70.1 years (59.2-81.4) for the others (p=0.001). Influenza-like illness had occurred during the 2 days before admission in 12 of the 16 PVL-positive patients, but in only three of 33 PVL-negative patients (p<0.001). PVL-positive infections were more often marked by: temperature greater than 39 degrees C (p=0.01), heart rate above 140 beats per min (p=0.02), haemoptysis (p=0.005), onset of pleural effusion during hospital stay (p=0.004), and leucopenia (p=0.001). The survival rate 48 h after admission was 63% for the PVL-positive patients and 94% for PVL-negative individuals (p=0.007). Histopathological examination of lungs at necropsy from three cases of necrotising pneumonia associated with PVL-positive S aureus showed extensive necrotic ulcerations of the tracheal and bronchial mucosa and massive haemorrhagic necrosis of interalveolar septa.
INTERPRETATION: PVL-producing S aureus strains cause rapidly progressive, haemorrhagic, necrotising pneumonia, mainly in otherwise healthy children and young adults. The pneumonia is often preceded by influenza-like symptoms and has a high lethality rate.

PMID 11888586  Lancet. 2002 Mar 2;359(9308):753-9. doi: 10.1016/S0140-・・・
著者: C L Nickerson, G J Jakab
雑誌名: Infect Immun. 1990 Sep;58(9):2809-14.
Abstract/Text Severe influenza virus infections with pneumonic involvement are known to predispose the lungs to bacterial superinfections due to dysfunctions in the alveolar macrophage (AM) phagocytic system. To determine whether milder forms of influenza without pneumonic involvement have a similar outcome, pulmonary antibacterial defenses and AM phagocytosis were compared in murine models of mild and severe influenza virus A/HK/68 infections. Bactericidal activity was quantitated by the intrapulmonary killing of Staphylococcus aureus following aerosol challenge, whereas the functional capacity of the AMs was determined by Fc-receptor-mediated phagocytosis. With the severe virus infection, maximal suppression of bactericidal activity occurred on day 8 of infection and correlated with impairment of AM phagocytosis. A lesser but significant degree of suppression of pulmonary antibacterial defenses and AM phagocytosis was observed on the third day of the mild virus infection. The data demonstrate that mild influenza virus infections that are limited to the upper respiratory tract also impair pulmonary antibacterial defenses and may predispose the lungs to bacterial superinfections.

PMID 2143751  Infect Immun. 1990 Sep;58(9):2809-14.
著者: M S Morgan
雑誌名: Int J Antimicrob Agents. 2007 Oct;30(4):289-96. doi: 10.1016/j.ijantimicag.2007.04.019. Epub 2007 Jul 12.
Abstract/Text Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus is emerging as a serious problem worldwide. Whilst usually causing skin and soft-tissue infections, particularly recurrent abscesses, there has in the last 10 years been an increase in the incidence of an associated devastating pneumonia affecting previously healthy young people and associated with a very high mortality. There are no evidence-based guidelines to consult for the management of PVL-associated staphylococcal pneumonia. The literature contains less than 100 cases, with widely differing antimicrobial therapies and the occasional use of other adjunctive therapies such as intravenous immunoglobulin, activated protein C and extracorporeal membrane oxygenation. This literature review focuses on the salient features of diagnosis and management, with particular attention to the choice of antimicrobials.

PMID 17629464  Int J Antimicrob Agents. 2007 Oct;30(4):289-96. doi: 10・・・
著者: R E Bryant, C J Salmon
雑誌名: Clin Infect Dis. 1996 May;22(5):747-62; quiz 763-4.
Abstract/Text
PMID 8722927  Clin Infect Dis. 1996 May;22(5):747-62; quiz 763-4.
著者: Chih-Hsuan Changchien, Ying-Ying Chen, Shu-Wun Chen, Wan-Lin Chen, Jwu-Guh Tsay, Chishih Chu
雑誌名: BMC Infect Dis. 2011 Oct 31;11:297. doi: 10.1186/1471-2334-11-297. Epub 2011 Oct 31.
Abstract/Text BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a prevalent pathogen of necrotizing fasciitis (NF) in Taiwan. A four-year NF cases and clinical and genetic differences between hospital acquired (HA)- and community-acquired (CA)-MRSA infection and isolates were investigated.
METHODS: A retrospective study of 247 NF cases in 2004-2008 and antimicrobial susceptibilities, staphylococcal chromosomal cassette mec (SCCmec) types, pulsed field gel electrophoresis (PFGE) patterns, virulence factors, and multilocus sequence typing (MLST) of 16 NF-associated MRSA in 2008 were also evaluated.
RESULTS: In 247 cases, 42 microbial species were identified. S. aureus was the major prevalent pathogen and MRSA accounted for 19.8% of NF cases. Most patients had many coexisting medical conditions, including diabetes mellitus, followed by hypertension, chronic azotemia and chronic hepatic disease in order of decreasing prevalence. Patients with MRSA infection tended to have more severe clinical outcomes in terms of amputation rate (p < 0.05) and reconstruction rate (p = 0.001) than those with methicillin-sensitive S. aureus or non-S. aureus infection. NF patients infected by HA-MRSA had a significantly higher amputation rate, comorbidity, C-reactive protein level, and involvement of lower extremity than those infected by CA-MRSA. In addition to over 90% of MRSA resistant to erythromycin and clindamycin, HA-MRSA was more resistant than CA-MRSA to trimethoprim-sulfamethoxazole (45.8% vs. 4%). ST59/pulsotype C/SCCmec IV and ST239/pulsotype A/SCCmec III isolates were the most prevalent CA- and HA-MRSA, respectively in 16 isolates obtained in 2008. In contrast to the gene for γ-hemolysin found in all MRSA, the gene for Panton-Valentine leukocidin was only identified in ST59 MRSA isolates. Other three virulence factors TSST-1, ETA, and ETB were occasionally identified in MRSA isolates tested.
CONCLUSION: NF patients with MRSA infection, especially HA-MRSA infection, had more severe clinical outcomes than those infected by other microbial. The prevalent NF-associated MRSA clones in Taiwan differed distinctly from the most predominant NF-associated USA300 CA-MRSA clone in the USA. Initial empiric antimicrobials with a broad coverage for MRSA should be considered in the treatment of NF patients in an endemic area.

PMID 22040231  BMC Infect Dis. 2011 Oct 31;11:297. doi: 10.1186/1471-2・・・
著者: Brian C Pien, Punidha Sundaram, Natalia Raoof, Sylvia F Costa, Stanley Mirrett, Christopher W Woods, L Barth Reller, Melvin P Weinstein
雑誌名: Am J Med. 2010 Sep;123(9):819-28. doi: 10.1016/j.amjmed.2010.03.021.
Abstract/Text BACKGROUND: Bloodstream infections are a major cause of morbidity and mortality in adults. Bloodstream infections should be reassessed periodically because of increased antibiotic resistance, more patients receiving immunomodulatory therapy, improved antiretroviral therapy, and acquisition of infection in health care settings other than hospitals.
METHODS: We conducted retrospective assessment by infectious disease physicians of hospitalized adults with positive blood cultures at 3 academic medical centers.
RESULTS: Two thousand two hundred seventy positive blood culture episodes occurred in 1706 patients. Of 2669 isolates, 51% represented true infection, 41% contamination, and 8% unknown clinical significance. Although coagulase-negative staphylococci were most common, only 10% were clinically significant. Among 1225 true bloodstream infections, the most frequent isolates were Staphylococcus aureus, Escherichia coli, Enterococcus spp., Klebsiella pneumoniae, coagulase-negative staphylococci, Pseudomonas aeruginosa, Candida albicans, Enterobacter cloacae, and Serratia marcescens. Intravenous catheters were the most common primary source of bloodstream infection (23% of episodes). Most (81%) bloodstream infections were acquired in the hospital or other health care settings. Crude and attributable in-hospital case-fatality ratios were 20% and 12%, respectively, lower than in previous studies. Increasing age, hypotension, absence of fever, hospital acquisition, extreme white blood cell count values, and the presence of the acquired immunodeficiency syndrome, malignancy, or renal disease were significantly associated with an increased risk of in-hospital attributable death in multivariable analysis.
CONCLUSIONS: The proportion of bloodstream infections due to intravenous catheters is continuing to increase. Most episodes were acquired in the hospital or other health care setting. In-hospital case-fatality ratios have decreased compared with previous studies. Several previously identified factors associated with an increased mortality remain statistically significant.

PMID 20800151  Am J Med. 2010 Sep;123(9):819-28. doi: 10.1016/j.amjmed・・・
著者: Alvaro Rea-Neto, Nazah Cherif M Youssef, Fabio Tuche, Frank Brunkhorst, V Marco Ranieri, Konrad Reinhart, Yasser Sakr
雑誌名: Crit Care. 2008;12(2):R56. doi: 10.1186/cc6877. Epub 2008 Apr 21.
Abstract/Text INTRODUCTION: Early, accurate diagnosis is fundamental in the management of patients with ventilator-associated pneumonia (VAP). The aim of this qualitative review was to compare various criteria of diagnosing VAP in the intensive care unit (ICU) with a special emphasis on the value of clinical diagnosis, microbiological culture techniques, and biomarkers of host response.
METHODS: A MEDLINE search was performed using the keyword 'ventilator associated pneumonia' AND 'diagnosis'. Our search was limited to human studies published between January 1966 and June 2007. Only studies of at least 25 adult patients were included. Predefined variables were collected, including year of publication, study design (prospective/retrospective), number of patients included, and disease group.
RESULTS: Of 572 articles fulfilling the initial search criteria, 159 articles were chosen for detailed review of the full text. A total of 64 articles fulfilled the inclusion criteria and were included in our review. Clinical criteria, used in combination, may be helpful in diagnosing VAP, however, the considerable inter-observer variability and the moderate performance should be taken in account. Bacteriologic data do not increase the accuracy of diagnosis as compared to clinical diagnosis. Quantitative cultures obtained by different methods seem to be rather equivalent in diagnosing VAP. Blood cultures are relatively insensitive to diagnose pneumonia. The rapid availability of cytological data, including inflammatory cells and Gram stains, may be useful in initial therapeutic decisions in patients with suspected VAP. C-reactive protein, procalcitonin, and soluble triggering receptor expressed on myeloid cells are promising biomarkers in diagnosing VAP.
CONCLUSION: An integrated approach should be followed in diagnosing and treating patients with VAP, including early antibiotic therapy and subsequent rectification according to clinical response and results of bacteriologic cultures.

PMID 18426596  Crit Care. 2008;12(2):R56. doi: 10.1186/cc6877. Epub 20・・・
著者: Kimberly A Davis, Matthew J Eckert, R Lawrence Reed, Thomas J Esposito, John M Santaniello, Stathis Poulakidas, Fred A Luchette
雑誌名: J Trauma. 2005 Mar;58(3):462-6; discussion 466-7.
Abstract/Text BACKGROUND: The results of sputum or bronchoalveolar lavage (BAL) fluid Gram's stain have been used to guide presumptive antibiotic therapy for ventilator-associated pneumonia (VAP) in injured patients, despite reported variability in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Our aim was to evaluate the utility of Gram's stain of BAL fluid in the diagnosis of VAP.
METHODS: We conducted a retrospective chart review of all mechanically ventilated trauma patients who developed pneumonia over a 5-year period in whom Gram's stain and final culture data were available.
RESULTS: One hundred fifty-five records with complete data sets were reviewed. VAP was diagnosed by Centers for Disease Control and Prevention criteria and confirmed by BAL and quantitative culture in all patients. Overall accuracy of Gram's stain in diagnosing VAP for any organism was 88% (137 true-positives). When assessed for the ability to predict pneumonia caused by a specific organism, the accuracy decreased significantly, with only 63% of Gram-negative VAPs and 72% of Gram-positive VAPs accurately identified by Gram's stain. However, the absence of Gram-positive organism of Gram's stain excludes Gram-positive VAP in 80% of patients.
CONCLUSION: All trauma patients should be covered presumptively for gram-negative organisms, as they encompass 70% of infections, but are not reliably identified by Gram's stain. As 88% of VAP can be identified by the presence of any organism on Gram's stain, it may be useful in the early diagnosis of VAP but cannot reliably be used to guide presumptive therapy.

PMID 15761337  J Trauma. 2005 Mar;58(3):462-6; discussion 466-7.
著者: Rodrigo Pires dos Santos, Caroline Deutschendorf, Fabiano Nagel, Loriane Konkewicz, Thiago Lisboa
雑誌名: Clin Infect Dis. 2013 Feb;56(4):616-7. doi: 10.1093/cid/cis904. Epub 2012 Oct 22.
Abstract/Text
PMID 23090933  Clin Infect Dis. 2013 Feb;56(4):616-7. doi: 10.1093/cid・・・
著者: Jumpei Yoshimura, Takahiro Kinoshita, Kazuma Yamakawa, Asako Matsushima, Naoki Nakamoto, Toshimitsu Hamasaki, Satoshi Fujimi
雑誌名: Crit Care. 2017 Jun 19;21(1):156. doi: 10.1186/s13054-017-1747-5. Epub 2017 Jun 19.
Abstract/Text BACKGROUND: Ventilator-associated pneumonia (VAP) is a common and serious problem in intensive care units (ICUs). Several studies have suggested that the Gram stain of endotracheal aspirates is a useful method for accurately diagnosing VAP. However, the usefulness of the Gram stain in predicting which microorganisms cause VAP has not been established. The purpose of this study was to evaluate whether a Gram stain of endotracheal aspirates could be used to determine appropriate initial antimicrobial therapy for VAP.
METHODS: Data on consecutive episodes of microbiologically confirmed VAP were collected from February 2013 to February 2016 in the ICU of a tertiary care hospital in Japan. We constructed two hypothetical empirical antimicrobial treatment algorithms for VAP: a guidelines-based algorithm (GLBA) based on the recommendations of the American Thoracic Society-Infectious Diseases Society of America (ATS-IDSA) guidelines and a Gram stain-based algorithm (GSBA) which limited the choice of initial antimicrobials according to the results of bedside Gram stains. The GLBA and the GSBA were retrospectively reviewed for each VAP episode. The initial coverage rates and the selection of broad-spectrum antimicrobial agents were compared between the two algorithms.
RESULTS: During the study period, 219 suspected VAP episodes were observed and 131 episodes were assessed for analysis. Appropriate antimicrobial coverage rates were not significantly different between the two algorithms (GLBA 95.4% versus GSBA 92.4%; p = 0.134). The number of episodes for which antimethicillin-resistant Staphylococcus aureus agents were selected as an initial treatment was larger in the GLBA than in the GSBA (71.0% versus 31.3%; p < 0.001), as were the number of episodes for which antipseudomonal agents were recommended as an initial treatment (70.2% versus 51.9%; p < 0.001).
CONCLUSIONS: Antimicrobial treatment based on Gram stain results may restrict the administration of broad-spectrum antimicrobial agents without increasing the risk of treatment failure.
TRIAL REGISTRATION: UMIN-CTR, UMIN000026457 . Registered 8 March 2017 (retrospectively registered).

PMID 28625166  Crit Care. 2017 Jun 19;21(1):156. doi: 10.1186/s13054-0・・・
著者: Liu Catherine C, Bayer Arnold A, Cosgrove Sara E SE, Daum Robert S RS, Fridkin Scott K SK, Gorwitz Rachel J RJ, Kaplan Sheldon L SL, Karchmer Adolf W AW, Levine Donald P DP, Murray Barbara E BE, J Rybak Michael M, Talan David A DA, Chambers Henry F HF, Infectious Diseases Society of America
雑誌名: Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4.
Abstract/Text Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

PMID 21208910  Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/・・・
著者: S J van Hal, T P Lodise, D L Paterson
雑誌名: Clin Infect Dis. 2012 Mar;54(6):755-71. doi: 10.1093/cid/cir935. Epub 2012 Feb 2.
Abstract/Text BACKGROUND: Emerging data suggest that vancomycin may be less effective against serious methicillin-resistant Staphylococcus aureus (MRSA) infections with minimum inhibitory concentration (MIC) values at the higher end of the susceptibility range. The purpose of this review is to examine the strength of these associations.
METHODS: All relevant studies pertaining to treatment outcomes or mortality associated with vancomycin MIC were retrieved from the medical literature from January 1996 through August 2011 and analyzed according to Cochrane guidelines.
RESULTS: Of the 270 studies identified, 48 studies were reviewed, with 22 studies included in the final meta-analysis. Vancomycin MIC was significantly associated with mortality for MRSA infection irrespective of the source of infection or MIC methodology (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.14-2.37; P < .01). This mortality association was predominantly driven by bloodstream infections (BSIs; OR, 1.58; 95% CI, 1.06-2.37; P = .03) and isolates with a vancomycin MIC of 2 μg/mL by Etest (OR, 1.72; 95% CI, 1.34-2.21; P < .01). Vancomycin MIC was significantly associated with treatment failure irrespective of source of infection or MIC methodology (OR, 2.69; 95% CI, 1.60-4.51; P < .01).
CONCLUSION: High vancomycin MIC was associated with a higher mortality rate in MRSA BSI. Thus, institutions should consider conducting Etest MICs on all MRSA BSI isolates. Although these data highlight concerns about vancomycin, currently, there are no data to support better survival rates with alternative antibiotics. Data are sorely needed to determine whether other agents can remedy these outcomes observed with vancomycin for MRSA infections with elevated vancomycin MIC values.

PMID 22302374  Clin Infect Dis. 2012 Mar;54(6):755-71. doi: 10.1093/ci・・・
著者: Andre C Kalil, Trevor C Van Schooneveld, Paul D Fey, Mark E Rupp
雑誌名: JAMA. 2014 Oct 15;312(15):1552-64. doi: 10.1001/jama.2014.6364.
Abstract/Text IMPORTANCE: Staphylococcus aureus bacteremia (SAB) is a worldwide problem. It is unclear whether higher-vancomycin minimum inhibitory concentration (MIC) is associated with mortality. This potential association has direct consequences for patients and public health.
DATA SOURCES: PubMed, Embase, the Cochrane Library, Evidence-based Medicine BMJ, and the American College of Physicians Journal Club were searched from inception through April 2014.
STUDY SELECTION: Studies reporting mortality and vancomycin MIC in patients with SAB were included.
DATA EXTRACTION AND SYNTHESIS: Two authors performed the literature search and the study selection separately. Random-effects modeling was used for all analyses.
MAIN OUTCOMES AND MEASURES: All-cause mortality.
FINDINGS: Among 38 included studies that involved 8291 episodes of SAB, overall mortality was 26.1%. The estimated mortality was 26.8% among SAB episodes (n = 2740) in patients with high-vancomycin MIC (≥1.5 mg/L) compared with 25.8% mortality among SAB episodes (n = 5551) in patients with low-vancomycin MIC (<1.5 mg/L) (adjusted risk difference [RD], 1.6% [95% CI, -2.3% to 5.6%]; P = .43). For the highest-quality studies, the estimated mortality was 26.2% among SAB episodes (n = 2318) in patients with high-vancomycin MIC compared with 27.8% mortality among SAB episodes (n = 4168) in patients with low-vancomycin MIC (RD, 0.9% [95% CI, -2.9% to 4.6%]; P = .65). In studies that included only methicillin-resistant S aureus infections (n = 7232), the mortality among SAB episodes (n = 2384) in patients with high-vancomycin MIC was 27.6% compared with mortality of 27.4% among SAB episodes (n = 4848) in patients with low-vancomycin MIC (adjusted RD, 1.6% [95% CI, -2.3% to 5.5%]; P = .41). No significant differences in risk of death were observed in subgroups with high-vancomycin MIC vs low-vancomycin MIC values across different study designs, microbiological susceptibility assays, MIC cutoffs, clinical outcomes, duration of bacteremia, previous vancomycin exposure, and treatment with vancomycin.
CONCLUSIONS AND RELEVANCE: In this meta-analysis of SAB episodes, there were no statistically significant differences in the risk of death when comparing patients with S aureus exhibiting high-vancomycin MIC (≥1.5 mg/L) to those with low-vancomycin MIC (<1.5 mg/L), although the findings cannot definitely exclude an increased mortality risk. These findings should be considered when interpreting vancomycin susceptibility and in determining whether alternative antistaphylococcal agents are necessary for patients with SAB with elevated but susceptible vancomycin MIC values.

PMID 25321910  JAMA. 2014 Oct 15;312(15):1552-64. doi: 10.1001/jama.20・・・
著者: R Diaz, V Afreixo, E Ramalheira, C Rodrigues, B Gago
雑誌名: Clin Microbiol Infect. 2017 Jun 23;. doi: 10.1016/j.cmi.2017.06.017. Epub 2017 Jun 23.
Abstract/Text OBJECTIVES: Vancomycin is currently the primary option treatment for methicillin-resistant Staphylococcus aureus (MRSA). However, an increasing number of MRSA isolates with high MICs, within the susceptible range (vancomycin MIC creep), are being reported worldwide. Resorting to a meta-analysis approach, this study aims to assess the evidence of vancomycin MIC creep.
METHODS: We searched for studies in the PubMed database. The inclusion criteria for study eligibility included the possibility of retrieving the reported data values of vancomycin MIC and information concerning the applied MIC methodology.
RESULTS: The mean values of vancomycin MICs, of all 29 234 S. aureus isolates reported in the 55 studies included in the meta-analysis, were 1.23 mg/L (95% CI 1.13-1.33) and 1.20 mg/L (95% CI 1.13-1.28) determined by Etest and broth microdilution method, respectively. No significant differences were observed between these two methodologies. We found negative correlation between pooled mean/pooled proportion and time strata.
CONCLUSIONS: We have found no evidence of the MIC creep phenomenon.

Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 28648858  Clin Microbiol Infect. 2017 Jun 23;. doi: 10.1016/j.cmi・・・
著者: Ronald N Jones
雑誌名: Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S13-24. doi: 10.1086/491710.
Abstract/Text The results of vancomycin susceptibility tests document that the drug continues to have activity against a wide variety of gram-positive pathogens. The subsequent emergence of vancomycin-resistant enterococci, the persistent failure of vancomycin therapy against strains tested as susceptible, and the more recent discoveries of vancomycin-intermediate or -resistant Staphylococcus aureus strains have compromised the use of vancomycin. Although analyses of surveillance studies fail to demonstrate "minimum inhibitory concentration creep" among populations of wild-type enterococci, streptococci, or staphylococci, enterococci with acquired resistance to vancomycin continue to evolve. The dominantly used automated commercial tests poorly recognize vancomycin-intermediate S. aureus, heteroresistant vancomycin-intermediate S. aureus, and vancomycin-resistant S. aureus isolates, which necessitates the use of expensive supplemental screening tests. Monitoring for appropriate serum levels of vancomycin and determinations of the bactericidal activity of vancomycin appear to best predict clinical outcome, thus creating additional diagnostic burdens for clinical laboratories. Improvements in current test methods with breakpoint criteria and expanded use of the vancomycin bactericidal assays to detect "tolerant" strains will be required to increase the value of vancomycin treatment or to refocus therapy toward the use of newer, alternative agents.

PMID 16323115  Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S13-24. doi: 10.・・・
著者: V Prakash, J S Lewis, J H Jorgensen
雑誌名: Antimicrob Agents Chemother. 2008 Dec;52(12):4528. doi: 10.1128/AAC.00904-08. Epub 2008 Oct 6.
Abstract/Text
PMID 18838599  Antimicrob Agents Chemother. 2008 Dec;52(12):4528. doi:・・・
著者: Juan-Ignacio Alós, Ana García-Cañas, Paloma García-Hierro, Francisco Rodríguez-Salvanés
雑誌名: J Antimicrob Chemother. 2008 Oct;62(4):773-5. doi: 10.1093/jac/dkn246. Epub 2008 Jun 13.
Abstract/Text OBJECTIVES: The aim of this study was to evaluate MIC trends for clinical isolates of Staphylococcus aureus to vancomycin over a 5 year period (2002-06) in a hospital in Spain.
METHODS: All clinical isolates of S. aureus (one per patient) from clinical samples of patients at Hospital Universitario de Getafe from January 2002 to December 2006 were used. MICs of vancomycin were determined by the CLSI broth microdilution procedure. For analysis of MIC trends over the 5 years, we grouped the isolates into those with MIC < or =1 mg/L [2428 methicillin-susceptible S. aureus (MSSA) and 518 methicillin-resistant S. aureus (MRSA)] and those with MIC > or =2 mg/L (MIC = 2 mg/L: 141 MSSA and 47 MRSA; MIC = 4 mg/L: 5 MSSA and 1 MRSA). MICs for the different groups in the different years were compared with the linear-trend chi(2) test.
RESULTS: A total of 3141 strains of S. aureus collected over the 5 year period was included in this analysis. Of these, 2574 (82%) strains were MSSA and 566 (18%) strains were MRSA. One of the 566 MRSA strains (0.18%) and 5 of the 2574 MSSA strains (0.19%) were vancomycin-intermediate (not significant). The rest were susceptible. The overall percentage of MRSA isolates with a vancomycin MIC of > or =2 mg/L was much higher than that of MSSA during the 5 year period [8.5% (48/566) versus 5.7% (146/2574); P = 0.012]. No statistically significant change in the percentage of isolates with a vancomycin MIC of > or =2 mg/L was observed over the years for MRSA (chi(2) = 0.01; P = 0.91) or MSSA (chi(2) = 0.08; P = 0.78). Annual consumption of parenteral vancomycin in our hospital in daily defined doses/100 stays was: 2002 (1.91), 2003 (1.63), 2004 (1.74), 2005 (2.06) and 2006 (1.64).
CONCLUSIONS: In a setting of low consumption of vancomycin and with a large collection of S. aureus clinical isolates, we have demonstrated the stability of vancomycin MICs over time.

PMID 18552338  J Antimicrob Chemother. 2008 Oct;62(4):773-5. doi: 10.1・・・
著者: Ethan Rubinstein, Marin H Kollef, Dilip Nathwani
雑誌名: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S378-85. doi: 10.1086/533594.
Abstract/Text A recent increase in staphylococcal infections caused by methicillin-resistant Staphylococcus aureus (MRSA), combined with frequent, prolonged ventilatory support of an aging, often chronically ill population, has resulted in a large increase in cases of MRSA pneumonia in the health care setting. In addition, community-acquired MRSA pneumonia has become more prevalent. This type of pneumonia historically affects younger patients, follows infection with influenza virus, and is often severe, requiring hospitalization and causing the death of a significant proportion of those affected. Ultimately, hospital-acquired MRSA and community-acquired MRSA are important causes of pneumonia and present diagnostic and therapeutic challenges. Rapid institution of appropriate antibiotic therapy, including linezolid as an alternative to vancomycin, is crucial. Respiratory infection-control measures and de-escalation of initial broad-spectrum antibiotic regimens to avoid emergence of resistant organisms are also important. This article reviews the clinical features of, diagnosis of, and therapies for MRSA pneumonia.

PMID 18462093  Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S378-85. doi: 10・・・
著者: Yves Gillet, Philippe Vanhems, Gerard Lina, Michele Bes, Francois Vandenesch, Daniel Floret, Jerome Etienne
雑誌名: Clin Infect Dis. 2007 Aug 1;45(3):315-21. doi: 10.1086/519263. Epub 2007 Jun 15.
Abstract/Text BACKGROUND: Necrotizing pneumonia due to Panton-Valentine leukocidin-producing strains of Staphylococcus aureus is associated with a high mortality rate. We sought factors associated with vital outcome in 50 cases occurring from 1986 through 2005.
METHODS: We compared the clinical and biological characteristics of 50 patients according to their vital outcome and examined the characteristics of the corresponding S. aureus isolates.
RESULTS: The overall mortality rate was 56%, and the median survival time was 10 days. All of the deaths were attributed to S. aureus infection and were secondary to refractory shock and/or respiratory failure. Fatal outcome was associated with classical severity factors, such as the need for mechanical ventilation or inotrope support, and with onset of the acute respiratory distress syndrome. Airway bleeding was strongly associated with fatal outcome (P=.002). Patients who had focal staphylococcal infection before the onset of pneumonia had a significantly lower mortality rate (P=.002). The main biological feature associated with death was leukopenia (P<.001). In multivariate analysis, leukopenia and erythroderma occurring within the first 24 h after admission to the hospital were independently associated with fatal outcome. Erythroderma was not associated with toxic shock syndrome toxin.
CONCLUSIONS: Airway bleeding, erythroderma, and leukopenia are associated with fatal outcome from Panton-Valentine leukocidin-positive S. aureus necrotizing pneumonia. More work is needed to develop more efficacious therapy against this highly lethal disease.

PMID 17599308  Clin Infect Dis. 2007 Aug 1;45(3):315-21. doi: 10.1086/・・・
著者: Michael J Rybak, Ben M Lomaestro, John C Rotschafer, Robert C Moellering, William A Craig, Marianne Billeter, Joseph R Dalovisio, Donald P Levine
雑誌名: Pharmacotherapy. 2009 Nov;29(11):1275-9.
Abstract/Text Vancomycin is a commonly used antibiotic due to its effectiveness in treating serious gram-positive infections caused by methicillin-resistant Staphylococcus aureus. As commercial drug assays and a multitude of pharmacokinetic data from a variety of patient populations are widely available, therapeutic monitoring of serum vancomycin concentrations is frequently performed by clinicians, with the expectation that targeting the concentrations within a relatively narrow range can minimize toxicity yet still achieve therapeutic success. Much debate exists, however, over the value of routine therapeutic monitoring of vancomycin levels because of conflicting evidence regarding the ability of serum concentrations to predict effectiveness or prevent toxicity. In addition, studies have suggested that the potential for nephrotoxicity or ototoxicity with vancomycin monotherapy is minimal at conventional dosages of 1 g (15 mg/kg) every 12 hours. However, increased rates of nephrotoxicity have recently been reported with doses of 4 g/day or higher. The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists published a consensus statement on therapeutic monitoring of serum vancomycin levels in adults. These organizations established an expert panel to review the scientific data and controversies associated with vancomycin monitoring and to make recommendations based on the available evidence. As the members of this panel, we summarize the conclusions and highlight the recommendations from the consensus statement. We determined that the area under the concentration-time curve (AUC): minimum inhibitory concentration (MIC) ratio is the most useful pharmacodynamic parameter to predict vancomycin effectiveness and suggested a target ratio of 400 or greater to eradicate S. aureus. In addition, trough serum concentration monitoring is the most accurate and practical method to monitor vancomycin serum levels. Increasing trough concentrations to 15-20 mg/L to attain the target AUC:MIC ratio may be desirable but is currently not supported by clinical trials. Alternative therapies should be considered in patients with S. aureus infections that demonstrate a vancomycin MIC of 2 mg/L or greater because the target AUC:MIC ratio ( 400) is unlikely to be achieved in this setting. Increasing the dosage to result in higher trough concentrations may increase the potential for toxicity; however additional clinical experience is required to determine the extent.

PMID 19873687  Pharmacotherapy. 2009 Nov;29(11):1275-9.
著者: Andre C Kalil, Mark L Metersky, Michael Klompas, John Muscedere, Daniel A Sweeney, Lucy B Palmer, Lena M Napolitano, Naomi P O'Grady, John G Bartlett, Jordi Carratalà, Ali A El Solh, Santiago Ewig, Paul D Fey, Thomas M File, Marcos I Restrepo, Jason A Roberts, Grant W Waterer, Peggy Cruse, Shandra L Knight, Jan L Brozek
雑誌名: Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.1093/cid/ciw353. Epub 2016 Jul 14.
Abstract/Text It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PMID 27418577  Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.109・・・
著者: Larry M Baddour, Walter R Wilson, Arnold S Bayer, Vance G Fowler, Imad M Tleyjeh, Michael J Rybak, Bruno Barsic, Peter B Lockhart, Michael H Gewitz, Matthew E Levison, Ann F Bolger, James M Steckelberg, Robert S Baltimore, Anne M Fink, Patrick O'Gara, Kathryn A Taubert, American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council
雑誌名: Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161/CIR.0000000000000296. Epub 2015 Sep 15.
Abstract/Text BACKGROUND: Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances.
METHODS AND RESULTS: This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations.
CONCLUSIONS: Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.

© 2015 American Heart Association, Inc.
PMID 26373316  Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161/・・・
著者: Dennis L Stevens, Alan L Bisno, Henry F Chambers, E Patchen Dellinger, Ellie J C Goldstein, Sherwood L Gorbach, Jan V Hirschmann, Sheldon L Kaplan, Jose G Montoya, James C Wade, Infectious Diseases Society of America
雑誌名: Clin Infect Dis. 2014 Jul 15;59(2):e10-52. doi: 10.1093/cid/ciu444.
Abstract/Text A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID 24973422  Clin Infect Dis. 2014 Jul 15;59(2):e10-52. doi: 10.1093・・・
著者: Catherine J Mathews, Gerald Coakley
雑誌名: Curr Opin Rheumatol. 2008 Jul;20(4):457-62. doi: 10.1097/BOR.0b013e3283036975.
Abstract/Text PURPOSE OF REVIEW: To propose and discuss an evidence-based algorithm for the diagnosis and treatment of bacterial septic arthritis. Also, to review the recent literature on emerging management strategies and discuss the potential impact of these developments on clinical practice.
RECENT FINDINGS: Evidence-based guidelines have recently been published to assist in the diagnosis and management of suspected and confirmed septic arthritis. All suspected septic joints should be aspirated and the synovial fluid examined by microscopy for the presence of crystals and microorganisms. There is controversy surrounding the diagnostic utility of quantifying the synovial fluid white cell count, with two recent systematic reviews reaching opposite conclusions. The emergence of multidrug resistant pathogens has led to a search for alternative antimicrobial agents such as linezolid. Studies in animals and children have suggested that corticosteroid therapy may be a useful adjunct to conventional antibiotic therapy. Research using experimental murine models of septic arthritis is also generating novel immunotherapeutic targets as potential adjuncts to antibiotic regimens.
SUMMARY: There is a striking paucity of high-quality evidence upon which to base guidelines on the management of the hot-swollen joint. Ultimately, the diagnosis of septic arthritis rests on the opinion of a clinician experienced in the assessment of musculoskeletal disease. Future research may provide alternative investigative and treatment strategies to improve the accuracy of diagnosis as well as the outcome in this group of patients.

PMID 18525361  Curr Opin Rheumatol. 2008 Jul;20(4):457-62. doi: 10.109・・・
著者: James S Lewis, James H Jorgensen
雑誌名: Clin Infect Dis. 2005 Jan 15;40(2):280-5. doi: 10.1086/426894. Epub 2004 Dec 21.
Abstract/Text The increasing incidence of a variety of infections due to Staphylococcus aureus--and, especially, the expanding role of community-associated methicillin-resistant S. aureus (MRSA)--has led to emphasis on the need for safe and effective agents to treat both systemic and localized staphylococcal infections. Unlike most previously noted strains of health care-associated MRSA, community-acquired MRSA isolates are often susceptible to several non- beta -lactam drug classes, although they are usually not susceptible to macrolides. Several newer antimicrobial agents and a few older agents are available for treatment of systemic staphylococcal infections, but use may be limited by the relatively high cost of these agents or the need for parenteral administration. Inexpensive oral agents for treatment of localized, community-acquired MRSA infection include clindamycin, trimethoprim-sulfamethoxazole, and newer tetracyclines. Clindamycin has been used successfully to treat pneumonia and soft-tissue and musculoskeletal infections due to MRSA in adults and children. However, concern over the possibility of emergence of clindamycin resistance during therapy has discouraged some clinicians from prescribing that agent. Simple laboratory testing (e.g., the erythromycin-clindamycin "D-zone" test) can separate strains that have the genetic potential (i.e., the presence of erm genes) to become resistant during therapy from strains that are fully susceptible to clindamycin.

PMID 15655748  Clin Infect Dis. 2005 Jan 15;40(2):280-5. doi: 10.1086/・・・
著者: Richard G Wunderink, Michael S Niederman, Marin H Kollef, Andrew F Shorr, Mark J Kunkel, Alice Baruch, William T McGee, Arlene Reisman, Jean Chastre
雑誌名: Clin Infect Dis. 2012 Mar 1;54(5):621-9. doi: 10.1093/cid/cir895. Epub 2012 Jan 12.
Abstract/Text BACKGROUND: Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia.
METHODS: This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated.
RESULTS: Of 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%).
CONCLUSIONS: For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.

PMID 22247123  Clin Infect Dis. 2012 Mar 1;54(5):621-9. doi: 10.1093/c・・・
著者: Andre C Kalil, Michael Klompas, Gleb Haynatzki, Mark E Rupp
雑誌名: BMJ Open. 2013 Oct 14;3(10):e003912. doi: 10.1136/bmjopen-2013-003912. Epub 2013 Oct 14.
Abstract/Text OBJECTIVE: Hospital-acquired pneumonia remains the most lethal and expensive nosocomial infection worldwide. Optimal therapy remains controversial. We aimed to compare mortality and clinical response outcomes in patients treated with either linezolid or vancomycin.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: PubMed, EMBASE, Cochrane Library, American College of Physicians Journal Club, Evidence-based Medicine BMJ and abstracts from infectious diseases and critical care meetings were searched through April 2013.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: All randomised clinical trials comparing linezolid to vancomycin for hospital-acquired pneumonia.
DATA EXTRACTION: Preferred reporting items for systematic reviews and meta-analyses guidelines were followed. One author extracted the data and two authors rechecked and verified all data.
RESULTS: Nine randomised trials with a total of 4026 patients were included. The adjusted absolute mortality risk difference (RD) between linezolid and vancomycin was 0.01% (95% CI -2.1% to 2.1%; p=0.992; I(2)=13.5%. The adjusted absolute clinical response difference was 0.9% (95% CI -1.2% to 3.1%; p=0.409; I(2)=0%. The risk of both microbiological (RD=5.6%, 95% CI -2.2% to 13.3%; p=0.159; I(2)=0%) and methicillin-resistant Staphylococcus aureus (RD=6.4%, 95% CI -4.1% to 16.9%; p=0.230; I(2)=0%) eradication were not different between linezolid and vancomycin. Gastrointestinal side effects were more frequent with linezolid (RD=0.8% (95% CI 0% to 1.5%; p=0.05), but no differences were found with renal failure, thrombocytopenia and drug discontinuation due to adverse events. Our sample size provided 99.9% statistical power to detect differences between drugs regarding clinical response and mortality.
CONCLUSIONS: Linezolid and vancomycin have similar efficacy and safety profiles. The high statistical power and the near-zero efficacy difference between both antibiotics demonstrates that no drug is superior for the treatment of hospital-acquired pneumonia.

PMID 24127058  BMJ Open. 2013 Oct 14;3(10):e003912. doi: 10.1136/bmjop・・・
著者: Yan Wang, Yamin Zou, Jiao Xie, Taotao Wang, Xiaowei Zheng, Hairong He, Weihua Dong, Jianfeng Xing, Yalin Dong
雑誌名: Eur J Clin Pharmacol. 2015 Jan;71(1):107-15. doi: 10.1007/s00228-014-1775-x. Epub 2014 Oct 30.
Abstract/Text PURPOSE: The optimal therapy involving linezolid or vancomycin for suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) remains controversial. This study compared the efficacy and safety of linezolid and vancomycin therapies in patients with NP.
METHODS: A systematic review of randomized controlled trials with meta-analyses performed by searching PubMed, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials. We screened for relevant randomized controlled studies in which patients with NP were enrolled and linezolid and vancomycin therapies were compared.
RESULTS: Nine trials involving 2618 pneumonia patients were reviewed. Linezolid was not found to be superior to vancomycin for clinical cure when categories of pathogen were not considered and in a subgroup of NP patients with MRSA infection [relative risk (RR)=1.16, 95 % confidence interval (CI)=0.95-1.43, P=0.15]. Compared with vancomycin, linezolid has no difference in the overall microbiological eradication rate (RR=1.12, 95 % CI=0.96-1.30, P=0.15) and specific MRSA eradication rate (RR=1.16, 95 % CI=0.93-1.45, P=0.19) in NP patients. In addition, nephrotoxicity was more frequent with vancomycin (RR=0.50, 95 % CI=0.31-0.81, P=0.005), but no differences between the treatments were found for all-cause mortality, thrombocytopenia, gastrointestinal effects, and drug discontinuation due to adverse events.
CONCLUSION: These results suggest that linezolid is not superior to vancomycin with respect to both clinical and microbiological cure rates in patients with MRSA NP.

PMID 25355172  Eur J Clin Pharmacol. 2015 Jan;71(1):107-15. doi: 10.10・・・
著者: Allan J Walkey, Max R O'Donnell, Renda Soylemez Wiener
雑誌名: Chest. 2011 May;139(5):1148-55. doi: 10.1378/chest.10-1556. Epub 2010 Sep 23.
Abstract/Text BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial pneumonia. Societal guidelines suggest linezolid may be the preferred treatment of MRSA nosocomial pneumonia. We investigated the efficacy of linezolid compared with glycopeptide antibiotics (vancomycin or teicoplanin) for nosocomial pneumonia.
METHODS: This was a systematic review and meta-analysis of English language, randomized, controlled trials comparing linezolid to glycopeptide antibiotics for suspected MRSA pneumonia in subjects > 12 years of age. A highly sensitive search of PubMed MEDLINE and Cochrane Central Register of Controlled Trials databases identified relevant studies.
RESULTS: Eight trials encompassing 1,641 subjects met entry criteria. Linezolid was not superior to glycopeptide antibiotics for end points of clinical success (relative risk [RR] linezolid vs glycopeptide, 1.04; 95% CI, 0.97-1.11; P = .28), microbiologic success (RR, 1.13; 95% CI, 0.97-1.31; P = .12), or mortality (RR, 0.91; 95% CI, 0.69-1.18; P = .47). In addition, clinical success in the subgroup of subjects with MRSA-positive respiratory tract culture (RR, 1.23; 95% CI, 0.97-1.57; P = .09) was not significantly different from those without MRSA (RR, 0.95; 95% CI, 0.83-1.09; P = .48), P for interaction, 0.07. The risk for adverse events was not different between the two antibiotic classes (RR, 0.96; 95% CI, 0.86-1.07; P = .48).
CONCLUSION: Randomized controlled trials do not support superiority of linezolid over glycopeptide antibiotics for the treatment of nosocomial pneumonia. We recommend that decisions between linezolid or glycopeptide antibiotics for empirical or MRSA-directed therapy of nosocomial pneumonia depend on local availability, antibiotic resistance patterns, preferred routes of delivery, and cost, rather than presumed differences in efficacy.

PMID 20864609  Chest. 2011 May;139(5):1148-55. doi: 10.1378/chest.10-1・・・
著者: Gregory Steinkraus, Roger White, Lawrence Friedrich
雑誌名: J Antimicrob Chemother. 2007 Oct;60(4):788-94. doi: 10.1093/jac/dkm258. Epub 2007 Jul 10.
Abstract/Text OBJECTIVES: To assess whether methicillin-resistant Staphylococcus aureus (MRSA) vancomycin MIC shifts (MIC creep) at a tertiary care institution occurred that may have gone undetected using traditional susceptibility markers (percentage susceptible, MIC(50), MIC(90)) over a 5 year period. Additionally, MIC trends were evaluated for oxacillin, linezolid and daptomycin.
METHODS: Etest MICs were performed on MRSA blood culture isolates (January 2001-December 2005). Only one isolate per patient was studied. The reported Etest MIC result was used and not rounded upward. MIC(50), MIC(90), median and geometric mean MIC, percentage susceptible and percentage resistant were calculated for each drug in each year. Non-parametric methods (linear correlation and Mantel-Haenszel chi(2)) were used to assess MIC trends over time and the association of vancomycin, linezolid and daptomycin MICs with oxacillin MICs.
RESULTS: All isolates were susceptible to vancomycin, linezolid and daptomycin and resistant to oxacillin. MICs increased for vancomycin, linezolid and oxacillin (P < 0.0001); however, daptomycin MICs decreased slightly (P = 0.0386). For vancomycin, linezolid and oxacillin, there were significant increases (P < 0.0001) in the percentage of isolates with MICs that were higher than the respective 2001 median MIC, but not for daptomycin (P = 0.1361). Oxacillin MICs were associated with MICs of linezolid (r = 0.364, P < 0.0001), vancomycin (r = 0.353, P < 0.0001) and daptomycin (r = 0.106, P = 0.0063).
CONCLUSIONS: Oxacillin, vancomycin and linezolid MICs increased over time. For vancomycin and linezolid, these MIC increases were not reliably detected by percentage susceptibility as they occurred below the susceptibility breakpoint. Although the MICs of all agents appeared to be associated with increasing oxacillin MICs, the strongest associations were noted for vancomycin and linezolid.

PMID 17623693  J Antimicrob Chemother. 2007 Oct;60(4):788-94. doi: 10.・・・
著者: George Sakoulas, Howard S Gold, Robert A Cohen, Lata Venkataraman, Robert C Moellering, George M Eliopoulos
雑誌名: J Antimicrob Chemother. 2006 Apr;57(4):699-704. doi: 10.1093/jac/dkl030. Epub 2006 Feb 7.
Abstract/Text OBJECTIVES: To evaluate microbiological properties of methicillin-resistant Staphylococcus aureus (MRSA) during prolonged vancomycin therapy.
METHODS: We evaluated vancomycin susceptibility and heteroresistance, accessory gene regulator (agr) function, autolysis, biofilm production and in vitro vancomycin killing in serial MRSA bloodstream isolates obtained over a 30 month period from a patient with a chronic endovascular infection.
RESULTS: Despite the fact that the MRSA in this patient had the same genetic background as other clinical glycopeptide intermediate-resistant S. aureus (GISA) isolates, vancomycin administered for 9 months, maintaining serum concentrations >10 mg/L, did not select for GISA. Minimal changes in vancomycin susceptibility were detected using agar dilution and population analysis methods. We noted increases in delta haemolysin production, autolysis and the bactericidal effects of vancomycin in vitro against the MRSA obtained after prolonged vancomycin suppressive therapy was discontinued.
CONCLUSIONS: Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.

PMID 16464892  J Antimicrob Chemother. 2006 Apr;57(4):699-704. doi: 10・・・
著者: Benjamin P Howden, Peter B Ward, Patrick G P Charles, Tony M Korman, Andrew Fuller, Philipp du Cros, Elizabeth A Grabsch, Sally A Roberts, Jenny Robson, Kerry Read, Narin Bak, James Hurley, Paul D R Johnson, Arthur J Morris, Barrie C Mayall, M Lindsay Grayson
雑誌名: Clin Infect Dis. 2004 Feb 15;38(4):521-8. doi: 10.1086/381202. Epub 2004 Jan 29.
Abstract/Text Although infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS) have been reported from a number of countries, including Australia, the optimal therapy is unknown. We reviewed the clinical features, therapy, and outcome of 25 patients with serious infections due to SA-RVS in Australia and New Zealand. Eight patients had endocarditis, 9 had bacteremia associated with deep-seated infection, 6 had osteomyelitis or septic arthritis, and 2 had empyema. All patients had received vancomycin before the isolation of SA-RVS, and glycopeptide treatment had failed for 19 patients (76%). Twenty-one patients subsequently received active treatment, which was effective for 16 patients (76%). Eighteen patients received linezolid, which was effective in 14 (78%), including 4 patients with endocarditis. Twelve patients received a combination of rifampicin and fusidic acid. Surgical intervention was required for 15 patients (60%). Antibiotic therapy, especially linezolid with or without rifampicin and fusidic acid, in conjunction with surgical debulking is effective therapy for the majority of patients with serious infections (including endocarditis) caused by SA-RVS.

PMID 14765345  Clin Infect Dis. 2004 Feb 15;38(4):521-8. doi: 10.1086/・・・
著者: Patrick G P Charles, Peter B Ward, Paul D R Johnson, Benjamin P Howden, M Lindsay Grayson
雑誌名: Clin Infect Dis. 2004 Feb 1;38(3):448-51. doi: 10.1086/381093. Epub 2004 Jan 12.
Abstract/Text We assessed all episodes of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia at our hospital during a 12-month period (n=53) and compared those due to heterogeneous vancomycin-intermediate S. aureus (hVISA; n = 5, 9.4%) with those due to vancomycin-susceptible MRSA (n=48). Patients with hVISA bacteremia were more likely to have high bacterial load infections (P=.001), vancomycin treatment failure (persistent fever and bacteremia for >7 days after the start of therapy; P<.001), and initially low serum vancomycin levels (P=.006). These clinical markers of hVISA bacteremia may help focus diagnostic efforts and treatment.

PMID 14727222  Clin Infect Dis. 2004 Feb 1;38(3):448-51. doi: 10.1086/・・・
著者: M W Climo, R L Patron, G L Archer
雑誌名: Antimicrob Agents Chemother. 1999 Jul;43(7):1747-53.
Abstract/Text Evidence of synergism between combinations of vancomycin and beta-lactam antibiotics against 59 isolates of methicillin-resistant staphylococci (Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus) for which vancomycin MICs ranged from 1 to 16 microg/ml were tested by broth microdilution checkerboard, disk diffusion, agar dilution, and time-kill antimicrobial susceptibility tests. The combination of vancomycin and oxacillin demonstrated synergy by all test methods against 30 of 59 isolates; no antagonism was seen. Synergy with vancomycin was also found by modified disk diffusion testing for ceftriaxone, ceftazidime, cefpodoxime, and amoxicillin-clavulanate but not for aztreonam. Evidence of synergy correlated directly with vancomycin MICs. The efficacy of vancomycin given alone and in combination with nafcillin was tested in the rabbit model of experimental endocarditis caused by three clinical isolates of glycopeptide-intermediate-susceptible S. aureus (GISA) (isolates HIP5827, HIP5836, and MU50). Two of the GISA isolates (isolates MU50 and HIP5836) were extremely virulent in this model, with 27 of 42 (64%) animals dying during the 3-day trial. Therapy with either vancomycin or nafcillin given as a single agent was ineffective for animals infected with HIP5827 or MU50. However, the combination of vancomycin and nafcillin resulted in a mean reduction of 4.52 log10 CFU/g of aortic valvular vegetations per g compared to the reduction for controls for animals infected with HIP5827 and a reduction of 4. 15 log10 CFU/g for animals infected with MU50. Renal abscesses caused by HIP5827 were sterilized significantly better with the combination of vancomycin and nafcillin than by either treatment alone. We conclude that the combination of vancomycin and beta-lactams with antistaphylococcal activity is an effective regimen for the treatment of infections with clinical strains of staphylococci which demonstrate reduced susceptibility to glycopeptides.

PMID 10390234  Antimicrob Agents Chemother. 1999 Jul;43(7):1747-53.
著者: Steven N Leonard
雑誌名: PLoS One. 2012;7(7):e42103. doi: 10.1371/journal.pone.0042103. Epub 2012 Jul 24.
Abstract/Text INTRODUCTION: Continued pressure from glycopeptide use has led to non-susceptible strains of Staphylococcus aureus including heterogeneously vancomycin-intermediate S. aureus (hVISA). Infections with hVISA are associated with poor patient outcomes, thus incentivizing novel treatments. Evidence suggests that vancomycin and anti-staphylococcal penicillin susceptibility are inversely related which indicates that the use of this combination may be particularly useful against methicillin-resistant S. aureus with reduced susceptibility to vancomycin, such as hVISA. The aim of this study was to evaluate the potential for synergy between vancomycin and nafcillin against hVISA.
METHODS: Twenty-five hVISA strains were evaluated for vancomycin and nafcillin minimum inhibitory concentration (MIC) by broth microdilution in duplicate. Potential for synergy was assessed by time-kill at 1/2x MIC in triplicate. Five strains were chosen, representing the range nafcillin MIC's available in the cohort -4, 16, 64, 128, and 256 µg/mL, and were run in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model in duplicate over 72 hours to evaluate the potential of the combination with simulated human pharmacokinetics. In addition, 4 fully glycopeptide susceptible strains of S. aureus including 2 methicillin-susceptible (MSSA) and 2 methicillin-resistant (MRSA) were run in the PK/PD model for comparison.
RESULTS: In the time-kill, 92% of strains (23 of 25) displayed synergy with the combination of vancomycin and nafcillin. In the PK/PD model, all five strains of hVISA showed an improvement in overall activity (P≤0.004) and organism burden at 72 hours (P≤0.001) with the combination compared to either drug alone. The combination was also successful against both MRSA and MSSA in overall activity (P≤0.009) and organism burden at 72 hours (P≤0.016), though the magnitude of the effect was diminished against MSSA.
CONCLUSIONS: The combination of vancomycin and nafcillin significantly improved antibacterial activity against hVISA, MRSA, and MSSA compared to either drug alone.

PMID 22848719  PLoS One. 2012;7(7):e42103. doi: 10.1371/journal.pone.0・・・
著者: Shrenik Mehta, Christopher Singh, Konrad B Plata, Palas K Chanda, Arundhati Paul, Sarah Riosa, Roberto R Rosato, Adriana E Rosato
雑誌名: Antimicrob Agents Chemother. 2012 Dec;56(12):6192-200. doi: 10.1128/AAC.01525-12. Epub 2012 Sep 17.
Abstract/Text Methicillin-resistant Staphylococcus aureus (MRSA) has emerged to be one of the most important pathogens both in health care and in community-onset infections. Daptomycin (DAP) is a cyclic anionic lipopeptide recommended for treatment of skin infections, bacteremia, and right-sided endocarditis caused by MRSA. Resistance to DAP (DAP(r)) has been reported in MRSA and is mostly accompanied by a parallel decrease in oxacillin resistance, a process known as the "seesaw effect." Our study provides evidence that the seesaw effect applies to other β-lactams and carbapenems of clinical use, including nafcillin (NAF), cefotaxime (CTX), amoxicillin-clavulanic (AMC), and imipenem (IMP), in heterogeneous DAP(r) MRSA strains but not in MRSA strains expressing homogeneous β-lactam resistance. The antibacterial efficacy of DAP in combination with β-lactams was evaluated in isogenic DAP-susceptible (DAP(s))/Dap(r) MRSA strains originally obtained from patients that failed DAP monotherapy. Both in vitro (MIC, synergy-kill curve) and in vivo (wax worm model) approaches were used. In these models, DAP and a β-lactam proved to be highly synergistic against both heterogeneous and homogeneous clinical DAP(r) MRSA strains. Mechanistically, β-lactams induced a reduction in the cell net positive surface charge, reverting the increased repulsion provoked by DAP alone, an effect that may favor the binding of DAP to the cell surface. The ease of in vitro mutant selection was observed when DAP(s) MRSA strains were exposed to DAP. Importantly, the combination of DAP and a β-lactam prevented the selection of DAP(r) variants. In summary, our data show that the DAP-β-lactam combination may significantly enhance both the in vitro and in vivo efficacy of anti-MRSA therapeutic options against DAP(r) MRSA infections and represent an option in preventing DAP(r) selection in persistent or refractory MRSA infections.

PMID 22985884  Antimicrob Agents Chemother. 2012 Dec;56(12):6192-200. ・・・
著者: Adriana Renzoni, William L Kelley, Roberto R Rosato, Maria P Martinez, Melanie Roch, Maryam Fatouraei, Daniel P Haeusser, William Margolin, Samuel Fenn, Robert D Turner, Simon J Foster, Adriana E Rosato
雑誌名: Antimicrob Agents Chemother. 2017 Jan;61(1). doi: 10.1128/AAC.01634-16. Epub 2016 Dec 27.
Abstract/Text Antimicrobial resistance is recognized as one of the principal threats to public health worldwide, yet the problem is increasing. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most difficult to treat in clinical settings due to the resistance of MRSA to nearly all available antibiotics. The cyclic anionic lipopeptide antibiotic daptomycin (DAP) is the clinical mainstay of anti-MRSA therapy. The decreased susceptibility to DAP (DAP resistance [DAPr]) reported in MRSA is frequently accompanied by a paradoxical decrease in β-lactam resistance, a process known as the "seesaw effect." Despite the observed discordance in resistance phenotypes, the combination of DAP and β-lactams has been proven to be clinically effective for the prevention and treatment of infections due to DAPr MRSA strains. However, the mechanisms underlying the interactions between DAP and β-lactams are largely unknown. In the study described here, we studied the role of mprF with DAP-induced mutations in β-lactam sensitization and its involvement in the effective killing by the DAP-oxacillin (OXA) combination. DAP-OXA-mediated effects resulted in cell wall perturbations, including changes in peptidoglycan insertion, penicillin-binding protein 2 (PBP 2) delocalization, and reduced membrane amounts of PBP 2a, despite the increased transcription of mecA through mec regulatory elements. We have found that the VraSR sensor-regulator is a key component of DAP resistance, triggering mutated mprF-mediated cell membrane (CM) modifications that result in impairment of PrsA location and chaperone functions, both of which are essential for PBP 2a maturation, the key determinant of β-lactam resistance. These observations provide for the first time evidence that synergistic effects between DAP and β-lactams involve PrsA posttranscriptional regulation of CM-associated PBP 2a.

Copyright © 2016 American Society for Microbiology.
PMID 27795377  Antimicrob Agents Chemother. 2017 Jan;61(1). doi: 10.11・・・
著者: Steven Y C Tong, Jane Nelson, David L Paterson, Vance G Fowler, Benjamin P Howden, Allen C Cheng, Mark Chatfield, Jeffrey Lipman, Sebastian Van Hal, Matthew O'Sullivan, James O Robinson, Dafna Yahav, David Lye, Joshua S Davis, CAMERA2 study group and the Australasian Society for Infectious Diseases Clinical Research Network
雑誌名: Trials. 2016 Mar 31;17:170. doi: 10.1186/s13063-016-1295-3. Epub 2016 Mar 31.
Abstract/Text BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia.
METHODS/DESIGN: We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint.
DISCUSSION: Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015.

PMID 27029920  Trials. 2016 Mar 31;17:170. doi: 10.1186/s13063-016-129・・・
著者: D P Levine, B S Fromm, B R Reddy
雑誌名: Ann Intern Med. 1991 Nov 1;115(9):674-80.
Abstract/Text OBJECTIVE: To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis.
DESIGN: Cohort analysis of a randomized study.
SETTING: University medical center.
PATIENTS: Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days.
MEASUREMENTS: Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia.
MAIN RESULTS: The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy.
CONCLUSIONS: Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.

PMID 1929035  Ann Intern Med. 1991 Nov 1;115(9):674-80.
著者: Guy E Thwaites, Matthew Scarborough, Alexander Szubert, Emmanuel Nsutebu, Robert Tilley, Julia Greig, Sarah A Wyllie, Peter Wilson, Cressida Auckland, Janet Cairns, Denise Ward, Pankaj Lal, Achyut Guleri, Neil Jenkins, Julian Sutton, Martin Wiselka, Gonzalez-Ruiz Armando, Clive Graham, Paul R Chadwick, Gavin Barlow, N Claire Gordon, Bernadette Young, Sarah Meisner, Paul McWhinney, David A Price, David Harvey, Deepa Nayar, Dakshika Jeyaratnam, Tim Planche, Jane Minton, Fleur Hudson, Susan Hopkins, John Williams, M Estee Török, Martin J Llewelyn, Jonathan D Edgeworth, A Sarah Walker, United Kingdom Clinical Infection Research Group (UKCIRG)
雑誌名: Lancet. 2018 Feb 17;391(10121):668-678. doi: 10.1016/S0140-6736(17)32456-X. Epub 2017 Dec 14.
Abstract/Text BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.
METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.
FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).
INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.
FUNDING: UK National Institute for Health Research Health Technology Assessment.

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID 29249276  Lancet. 2018 Feb 17;391(10121):668-678. doi: 10.1016/S0・・・
著者: David J Riedel, Elizabeth Weekes, Graeme N Forrest
雑誌名: Antimicrob Agents Chemother. 2008 Jul;52(7):2463-7. doi: 10.1128/AAC.00300-08. Epub 2008 May 12.
Abstract/Text Staphylococcus aureus is a common cause of native valve infective endocarditis (IE). Rifampin is often added to traditional therapy for the management of serious S. aureus infections. There are no large, prospective studies documenting the safety and efficacy of adjunctive therapy with rifampin for treatment of native valve S. aureus IE. We reviewed all cases of definite native valve S. aureus IE confirmed by modified Duke criteria in a large urban hospital between 1 January 2004 and 31 December 2005. A retrospective cohort analysis was used to assess the impact of the addition of rifampin to standard therapy. There were 42 cases of S. aureus IE treated with the addition of rifampin and 42 controls. Cases received a median of 20 days of rifampin (range, 14 to 48 days). Rifampin-resistant S. aureus isolates developed in nine cases who received rifampin before clearance of bacteremia (56%), while significant hepatic transaminase elevations also occurred in nine cases, all of whom had hepatitis C infection. Unrecognized significant drug-drug interactions with rifampin occurred frequently (52%). Cases were more likely to have a longer duration of bacteremia (5.2 versus 2.1 days; P < 0.001) and were less likely to survive (79% versus 95%; P = 0.048) than controls. Our results suggest that the potential for hepatotoxicity, drug-drug interactions, and the emergence of resistant S. aureus isolates warrants a careful risk-benefit assessment before adding rifampin to standard antibiotic treatment of native valve S. aureus IE until further clinical studies are performed.

PMID 18474578  Antimicrob Agents Chemother. 2008 Jul;52(7):2463-7. doi・・・
著者: C Watanakunakorn, J C Tisone
雑誌名: Antimicrob Agents Chemother. 1982 Nov;22(5):903-5.
Abstract/Text By the time-kill curve method, the combinations of vancomycin-gentamicin and vancomycin-tobramycin were shown to be synergistic against a majority of methicillin-susceptible and -resistant strains of Staphylococcus aureus.

PMID 6924825  Antimicrob Agents Chemother. 1982 Nov;22(5):903-5.
著者: O Korzeniowski, M A Sande
雑誌名: Ann Intern Med. 1982 Oct;97(4):496-503.
Abstract/Text Single (nafcillin for 6 weeks) and combined (nafcillin for 6 weeks plus gentamicin for 2 weeks) drug regimens were compared in two separate multicenter prospective randomized trials. Forty-eight parenteral drug addicts and 30 nonaddicts with clinically and bacteriologically documented Staphylococcus aureus endocarditis were studied. In the addicts, combined therapy effected a more rapid mean clinical response (defervescence and normalization of leukocyte count) and a reduced duration of bacteremia in patients with right-sided endocarditis. In the nonaddicts, combined therapy effected more rapid clearance of bacteremia, but was associated with a higher incidence of azotemia. The addition of gentamicin did not alter morbidity or mortality in either group.

PMID 6751182  Ann Intern Med. 1982 Oct;97(4):496-503.
著者: Sara E Cosgrove, Gloria A Vigliani, Vance G Fowler, Elias Abrutyn, G Ralph Corey, Donald P Levine, Mark E Rupp, Henry F Chambers, Adolf W Karchmer, Helen W Boucher
雑誌名: Clin Infect Dis. 2009 Mar 15;48(6):713-21. doi: 10.1086/597031.
Abstract/Text BACKGROUND: The safety of adding initial low-dose gentamicin to antistaphylococcal penicillins or vancomycin for treatment of suspected Staphylococcus aureus native valve endocarditis is unknown. This study evaluated the association between this practice and nephrotoxicity.
METHODS: We performed a prospective cohort study of safety data from a randomized, controlled trial of therapy for S. aureus bacteremia and native valve infective endocarditis involving 236 patients from 44 hospitals in 4 countries. Patients either received standard therapy (antistaphylococcal penicillin or vancomycin) plus initial low-dose gentamicin (n=116) or received daptomycin monotherapy (n = 120). We measured renal adverse events and clinically significant decreased creatinine clearance in patients (1) in the original randomized study arms and (2) who received any initial low-dose gentamicin either, as a study medication or RESULTS: Renal adverse events occurred in 8 (7%) of 120 daptomycin recipients, 10 (19%) of 53 vancomycin recipients, and 11 (17%) of 63 antistaphylococcal penicillin recipients. Decreased creatinine clearance occurred in 9 (8%) of 113 of evaluable daptomycin recipients, 10 (22%) of 46 vancomycin recipients, and 16 (25%) of 63 antistaphylococcal penicillin recipients. An additional 21 patients received initial low-dose gentamicin or=65 years and receipt of any initial low-dose gentamicin.
CONCLUSIONS: Initial low-dose gentamicin as part of therapy for S. aureus bacteremia and native valve infective endocarditis is nephrotoxic and should not be used routinely, given the minimal existing data supporting its benefit.

PMID 19207079  Clin Infect Dis. 2009 Mar 15;48(6):713-21. doi: 10.1086・・・
著者: Susan J Rehm, Helen Boucher, Donald Levine, Marilyn Campion, Barry I Eisenstein, Gloria A Vigliani, G Ralph Corey, Elias Abrutyn
雑誌名: J Antimicrob Chemother. 2008 Dec;62(6):1413-21. doi: 10.1093/jac/dkn372. Epub 2008 Sep 8.
Abstract/Text OBJECTIVES: In a prospective, randomized trial, daptomycin was non-inferior to standard therapy for Staphylococcus aureus bacteraemia and right-sided endocarditis. Since rates of infection due to methicillin-resistant S. aureus (MRSA) infection are increasing and treatment outcomes for bacteraemia caused by MRSA are generally worse than those observed with methicillin-susceptible S. aureus bacteraemia, clinical characteristics and treatment results in the trial's pre-specified subset of patients with MRSA were analysed.
METHODS: Clinical characteristics and outcomes of patients receiving daptomycin were compared with those receiving vancomycin plus low-dose gentamicin. Success was defined as clinical improvement with clearance of bacteraemia among patients who completed adequate therapy, received no potentially effective non-study antibiotics and had negative blood cultures 6 weeks after end of therapy.
RESULTS: Twenty of the 45 (44.4%) daptomycin patients and 14 of the 43 (32.6%) vancomycin/gentamicin patients were successfully treated (difference 11.9%; confidence interval -8.3 to 32.1). Success rates for daptomycin versus vancomycin/gentamicin were 45% versus 27% in complicated bacteraemia, 60% versus 45% in uncomplicated bacteraemia and 50% versus 50% in right-sided MRSA endocarditis. Cure rates in patients with septic emboli and in patients who received pre-enrolment vancomycin were similar between treatment groups. However, in both treatment groups, success rates were lower in the elderly (>/=75 years). Persisting or relapsing bacteraemia occurred in 27% of daptomycin and 21% of vancomycin/gentamicin patients; among these patients, MICs of >/=2 mg/L occurred in five daptomycin and four vancomycin/gentamicin patients. The clinical course of several patients may have been influenced by lack of surgical intervention.
CONCLUSIONS: Daptomycin was an effective alternative to vancomycin/gentamicin for MRSA bacteraemia or right-sided endocarditis.

PMID 18782781  J Antimicrob Chemother. 2008 Dec;62(6):1413-21. doi: 10・・・
著者: Bruno Hoen, Xavier Duval
雑誌名: N Engl J Med. 2013 Apr 11;368(15):1425-33. doi: 10.1056/NEJMcp1206782.
Abstract/Text
PMID 23574121  N Engl J Med. 2013 Apr 11;368(15):1425-33. doi: 10.1056・・・
著者: Helio S Sader, Rodrigo E Mendes, Jennifer M Streit, Robert K Flamm
雑誌名: Antimicrob Agents Chemother. 2017 Sep;61(9). doi: 10.1128/AAC.01043-17. Epub 2017 Aug 24.
Abstract/Text We evaluated trends in Staphylococcus aureus antimicrobial susceptibility in U.S. hospitals in the 2010-2016 period. A total of 21,056 clinical isolates from 42 medical centers were tested for susceptibility by broth microdilution methods. Methicillin-resistant S. aureus (MRSA) rates decreased from 50.0% (in 2010) to 42.2% (in 2016). Susceptibility to erythromycin, levofloxacin, and clindamycin increased slightly, whereas susceptibility to ceftaroline, trimethoprim-sulfamethoxazole, and tetracycline remained stable. Ceftaroline retained potent activity against methicillin-susceptible S. aureus (MSSA) and MRSA (97.2% susceptible) with no marked variations.

Copyright © 2017 American Society for Microbiology.
PMID 28630196  Antimicrob Agents Chemother. 2017 Sep;61(9). doi: 10.11・・・
著者: Bing Gu, Theodoros Kelesidis, Sotirios Tsiodras, Janet Hindler, Romney M Humphries
雑誌名: J Antimicrob Chemother. 2013 Jan;68(1):4-11. doi: 10.1093/jac/dks354. Epub 2012 Sep 4.
Abstract/Text The oxazolidinone antibiotic linezolid has demonstrated potent antimicrobial activity against Gram-positive bacterial pathogens, including methicillin-resistant staphylococci. This article systematically reviews the published literature for reports of linezolid-resistant Staphylococcus (LRS) infections to identify epidemiological, microbiological and clinical features for these infections. Linezolid remains active against >98% of Staphylococcus, with resistance identified in 0.05% of Staphylococcus aureus and 1.4% of coagulase-negative Staphylococcus (CoNS). In all reported cases, patients were treated with linezolid prior to isolation of LRS, with mean times of 20.0 ± 47.0 months for S. aureus and 11.0 ± 8.0 days for CoNS. The most common mechanisms for linezolid resistance were mutation (G2576T) to the 23S rRNA (63.5% of LRSA and 60.2% of LRCoNS) or the presence of a transmissible cfr ribosomal methyltransferase (54.5% of LRSA and 15.9% of LRCoNS). The emergence of linezolid resistance in Staphylococcus poses significant challenges to the clinical treatment of infections caused by these organisms, and in particular CoNS.

PMID 22949625  J Antimicrob Chemother. 2013 Jan;68(1):4-11. doi: 10.10・・・
著者: Gracia Morales, Juan J Picazo, Elvira Baos, Francisco J Candel, Ana Arribi, Beatriz Peláez, Raquel Andrade, María-Angeles de la Torre, José Fereres, Miguel Sánchez-García
雑誌名: Clin Infect Dis. 2010 Mar 15;50(6):821-5. doi: 10.1086/650574.
Abstract/Text BACKGROUND: From April through June 2008, we identified 12 patients in the intensive care unit and 3 patients on other wards infected with methicillin-resistant Staphylococcus aureus that was also resistant to linezolid. We investigated the mechanism of resistance--point mutations in domain V of 23S ribosomal RNA (rRNA) or presence of the cfr gene--involved in the outbreak.
METHODS: Strains for the study were obtained in the intensive care unit and other wards. Minimal inhibitory concentrations were determined using automated methods, the E-test, or dilution in Mueller-Hinton agar in accordance with Clinical and Laboratory Standards Institute guidelines. Strains were genotyped using pulsed-field gel electrophoresis and were sequenced to determine the presence of point mutations in 23S rRNA. The presence of the cfr gene was determined by specific polymerase chain reaction.
RESULTS: The minimal inhibitory concentrations of linezolid ranged from 16 mg/L to 32 mg/L, and all the strains were susceptible to tigecycline, vancomycin, and daptomycin. Typing of strains sequentially isolated by pulsed-field gel electrophoresis showed that each patient carried only 1 clonal type of linezolid-resistant, methicillin-resistant S. aureus as detected by sequential isolations. The presence of the cfr gene was confirmed in all the isolates. Furthermore, sequencing of domain V of 23S rRNA showed that the most common mechanism of linezolid resistance reported to date, mutation G2576T, was not detected in any of the strains analyzed.
CONCLUSIONS: We report the presence of the cfr gene underlying the resistance mechanism involved in a clinical outbreak of linezolid-resistant S. aureus.

PMID 20144045  Clin Infect Dis. 2010 Mar 15;50(6):821-5. doi: 10.1086/・・・
著者: Jean B Patel, Laura A Jevitt, Jeffery Hageman, L Clifford McDonald, Fred C Tenover
雑誌名: Clin Infect Dis. 2006 Jun 1;42(11):1652-3. doi: 10.1086/504084.
Abstract/Text
PMID 16652325  Clin Infect Dis. 2006 Jun 1;42(11):1652-3. doi: 10.1086・・・
著者: Miguel Sánchez García, María Angeles De la Torre, Gracia Morales, Beatriz Peláez, María José Tolón, Sara Domingo, Francisco Javier Candel, Raquel Andrade, Ana Arribi, Nicolás García, Fernando Martínez Sagasti, José Fereres, Juan Picazo
雑誌名: JAMA. 2010 Jun 9;303(22):2260-4. doi: 10.1001/jama.2010.757.
Abstract/Text CONTEXT: Linezolid resistance is extremely uncommon in Staphylococcus aureus.
OBJECTIVE: To report an outbreak with linezolid and methicillin-resistant S. aureus (LRSA) in an intensive care department and the effective control measures taken.
DESIGN, SETTING, AND PATIENTS: Outbreak study of consecutive critically ill patients colonized and/or infected with LRSA at an intensive care department of a 1000-bed tertiary care university teaching hospital in Madrid, Spain. Patients were placed under strict contact isolation. Daily updates of outbreak data and recommendations for the use of linezolid were issued. Extensive environmental sampling and screening of the hands of health care workers were performed.
MAIN OUTCOME MEASURES: Linezolid use and clinical and epidemiological characteristics and outcomes using minimal inhibitory concentrations, pulsed-field gel electrophoresis, and polymerase chain reaction of LRSA isolates.
RESULTS: Between April 13 and June 26, 2008, 12 patients with LRSA were identified. In 6 patients, LRSA caused ventilator-associated pneumonia and in 3 patients it caused bacteremia. Isolates were susceptible to trimethoprim-sulfamethoxazole, glycopeptides, tigecycline, and daptomycin. Genotyping identified 1 predominant clone and 3 other types. Cfr-mediated linezolid resistance was demonstrated in all isolates. Potential hospital staff carriers and environmental samples were negative except for one. Six patients died, 5 of them in the intensive care unit, with 1 death attributed to LRSA infection. Linezolid use decreased from 202 defined daily doses in April 2008 to 25 defined daily doses in July 2008. Between July 2008 and April 2010, no new cases have been identified in the weekly surveillance cultures or diagnostic samples.
CONCLUSIONS: The first clinical outbreak, to our knowledge, with LRSA mediated by the cfr gene developed at our center, was associated with nosocomial transmission and extensive usage of linezolid. Reduction of linezolid use and infection-control measures were associated with the termination of the outbreak.

PMID 20530779  JAMA. 2010 Jun 9;303(22):2260-4. doi: 10.1001/jama.2010・・・
著者: Megan K Luther, Tristan T Timbrook, Aisling R Caffrey, David Dosa, Thomas P Lodise, Kerry L LaPlante
雑誌名: Crit Care Med. 2018 Jan;46(1):12-20. doi: 10.1097/CCM.0000000000002769.
Abstract/Text OBJECTIVES: The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy.
DATA SOURCES: Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched.
STUDY SELECTION: Articles not in English, pediatric studies, and case reports were excluded.
DATA EXTRACTION: Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3.
DATA SYNTHESIS: Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, -1.30; 95% CI, -3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57-4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83-3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97-3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48-20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83-2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86-2.11).
CONCLUSIONS: The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.

PMID 29088001  Crit Care Med. 2018 Jan;46(1):12-20. doi: 10.1097/CCM.0・・・
著者: Shuli Svetitsky, Leonard Leibovici, Mical Paul
雑誌名: Antimicrob Agents Chemother. 2009 Oct;53(10):4069-79. doi: 10.1128/AAC.00341-09. Epub 2009 Jul 13.
Abstract/Text Vancomycin and teicoplanin are the glycopeptides currently in use for the treatment of infections caused by invasive beta-lactam-resistant gram-positive organisms. We conducted a systematic review and meta-analysis of randomized controlled trials that have compared vancomycin and teicoplanin administered systemically for the treatment of suspected or proven infections. A comprehensive search of trials without year, language, or publication status restrictions was performed. The primary outcome was all-cause mortality. Two reviewers independently extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled by using the fixed-effect model (RRs of >1 favor vancomycin). Twenty-four trials were included. All-cause mortality was similar overall (RR, 0.95; 95% CI, 0.74 to 1.21), and there was no significant heterogeneity. In trials that used adequate allocation concealment, the results favored teicoplanin (RR, 0.82; 95% CI, 0.63 to 1.06), while in trials with unknown methods or inadequate concealment, the results favored vancomycin (RR, 3.61; 95% CI, 1.27 to 10.30). The latter trials might have recruited more severely ill patients. No other variable affected the RRs for mortality, including the assessment of glycopeptides administered empirically or for proven infections, neutropenia, the participant's age, and drug dosing. There were no significant differences between teicoplanin and vancomycin with regard to clinical failure (RR, 0.92; 95% CI, 0.81 to 1.05), microbiological failure (RR, 1.24; 95% CI, 0.93 to 1.65), and other efficacy outcomes. Lower RRs (in favor of teicoplanin) for clinical failure were observed with a lower risk of bias and when treatment was initiated for infections caused by gram-positive organisms rather than empirically. Total adverse events (RR, 0.61; 95% CI, 0.50 to 0.74), nephrotoxicity (RR, 0.44; 95% CI, 0.32 to 0.61), and red man syndrome were significantly less frequent with teicoplanin. Teicoplanin is not inferior to vancomycin with regard to efficacy and is associated with a lower adverse event rate than vancomycin.

PMID 19596875  Antimicrob Agents Chemother. 2009 Oct;53(10):4069-79. d・・・
著者: Alexandre B Cavalcanti, Anderson R Goncalves, Claudia S Almeida, Diogo Dg Bugano, Eliezer Silva
雑誌名: Cochrane Database Syst Rev. 2010 Jun 16;(6):CD007022. doi: 10.1002/14651858.CD007022.pub2. Epub 2010 Jun 16.
Abstract/Text BACKGROUND: Vancomycin and teicoplanin are commonly used to treat gram-positive infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). There is uncertainty regarding the effects of teicoplanin compared to vancomycin on kidney function with some previous studies suggesting teicoplanin is less nephrotoxic than vancomycin.
OBJECTIVES: To investigate the efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection.
SEARCH STRATEGY: We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, reference lists of nephrology textbooks, review articles with relevant studies and sent letters seeking information about unpublished or incomplete studies to investigators involved in previous studies.
SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection.
DATA COLLECTION AND ANALYSIS: Two authors independently evaluated methodological quality and extracted data using standardised data extraction forms. Study investigators were contacted for information not available in the original manuscripts. Random effects model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI).
MAIN RESULTS: We included 24 studies (2,610 patients) in this review. Teicoplanin reduced the risk of nephrotoxicity compared to vancomycin (RR 0.66, 95% CI 0.48 to 0.90).The effects of teicoplanin or vancomycin were similar for clinical cure (RR 1.03, 95% CI 0.98 to 1.08), microbiological cure (RR 0.98, 95% CI 0.93 to 1.03) and mortality (RR 1.02, 95% CI 0.79 to1.30). Six studies reported no cases of acute kidney injury (AKI) needing dialysis. Adverse events were less frequent with teicoplanin including cutaneous rash (RR 0.57, 95% CI 0.35 to 0.92), red man syndrome (RR 0.21, 95% CI 0.08 to 0.59) and total adverse events (RR 0.73, 95% CI 0.53 to 1.00). A lower risk of nephrotoxicity with teicoplanin was observed in patients either with (RR 0.51, 95% CI 0.30 to 0.88) or without aminoglycosides (RR 0.31, 95% 0.07 to 1.50), and also when vancomycin dosing was guided by serum levels (RR 0.22, 95% CI 0.10 to 0.52).
AUTHORS' CONCLUSIONS: Teicoplanin and vancomycin are both effective in treating those with proven or suspected infection; however the incidence of adverse effects including nephrotoxicity was lower with teicoplanin. There were no cases of AKI needing dialysis. It remains unclear whether the differential effect on kidney function should influence which antibiotic be prescribed, although it may be reasonable to consider teicoplanin for patients at higher risk for AKI needing dialysis.

PMID 20556772  Cochrane Database Syst Rev. 2010 Jun 16;(6):CD007022. d・・・
著者: Romney M Humphries, Simon Pollett, George Sakoulas
雑誌名: Clin Microbiol Rev. 2013 Oct;26(4):759-80. doi: 10.1128/CMR.00030-13.
Abstract/Text Daptomycin is a lipopeptide antimicrobial with in vitro bactericidal activity against Gram-positive bacteria that was first approved for clinical use in 2004 in the United States. Since this time, significant data have emerged regarding the use of daptomycin for the treatment of serious infections, such as bacteremia and endocarditis, caused by Gram-positive pathogens. However, there are also increasing reports of daptomycin nonsusceptibility, in Staphylococcus aureus and, in particular, Enterococcus faecium and Enterococcus faecalis. Such nonsusceptibility is largely in the context of prolonged treatment courses and infections with high bacterial burdens, but it may occur in the absence of prior daptomycin exposure. Nonsusceptibility in both S. aureus and Enterococcus is mediated by adaptations to cell wall homeostasis and membrane phospholipid metabolism. This review summarizes the data on daptomycin, including daptomycin's unique mode of action and spectrum of activity and mechanisms for nonsusceptibility in key pathogens, including S. aureus, E. faecium, and E. faecalis. The challenges faced by the clinical laboratory in obtaining accurate susceptibility results and reporting daptomycin MICs are also discussed.

PMID 24092854  Clin Microbiol Rev. 2013 Oct;26(4):759-80. doi: 10.1128・・・
著者: Pamela A Moise, Donald North, Judith N Steenbergen, George Sakoulas
雑誌名: Lancet Infect Dis. 2009 Oct;9(10):617-24. doi: 10.1016/S1473-3099(09)70200-2.
Abstract/Text The decrease in vancomycin treatment efficacy that is accompanying increases in vancomycin minimum inhibitory concentration (MIC) within the susceptible range (so-called MIC creep) has led to the suggestion that vancomycin is losing its potency in treating serious Staphylococcus aureus infections. Understanding the clinical importance of the microbiological effects of glycopeptides on bacterial lipopeptides and lipoglycopeptides will be crucial in treating serious meticillin-resistant S aureus infections. We review the observed effects of reduced glycopeptide susceptibility on the activities of daptomycin in S aureus in vitro and in vivo. Factors associated with loss of susceptibility and ways to reduce the risk of resistance to daptomycin are reviewed, including the importance of prompt mechanical reduction of bacterial inoculum through surgery or through potent or combination antibiotic therapy, as well as optimisation of daptomycin pharmacodynamic exposure.

PMID 19778764  Lancet Infect Dis. 2009 Oct;9(10):617-24. doi: 10.1016/・・・
著者: Darren Culshaw, Kenneth C Lamp, Min J Yoon, Thomas P Lodise
雑誌名: Diagn Microbiol Infect Dis. 2015 Oct;83(2):193-7. doi: 10.1016/j.diagmicrobio.2015.06.003. Epub 2015 Jun 11.
Abstract/Text The association between varying durations of previous vancomycin therapy and subsequent daptomycin success rates was evaluated in a subset of patients with methicillin-resistant Staphylococcus aureus bacteremia from the Cubicin® Outcomes Registry and Experience 2005-2009 (n=159). Previous vancomycin exposure did not adversely affect daptomycin outcomes; success rates were 81% in patients treated with first-line daptomycin and 89%, 83%, and 88%, respectively, in patients with 1-3days, 4-6days, and ≥7days of previous vancomycin exposure (P=0.5).

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID 26184127  Diagn Microbiol Infect Dis. 2015 Oct;83(2):193-7. doi: ・・・
著者: Vance G Fowler, Helen W Boucher, G Ralph Corey, Elias Abrutyn, Adolf W Karchmer, Mark E Rupp, Donald P Levine, Henry F Chambers, Francis P Tally, Gloria A Vigliani, Christopher H Cabell, Arthur Stanley Link, Ignace DeMeyer, Scott G Filler, Marcus Zervos, Paul Cook, Jeffrey Parsonnet, Jack M Bernstein, Connie Savor Price, Graeme N Forrest, Gerd Fätkenheuer, Marcelo Gareca, Susan J Rehm, Hans Reinhardt Brodt, Alan Tice, Sara E Cosgrove, S. aureus Endocarditis and Bacteremia Study Group
雑誌名: N Engl J Med. 2006 Aug 17;355(7):653-65. doi: 10.1056/NEJMoa053783.
Abstract/Text BACKGROUND: Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed.
METHODS: We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy.
RESULTS: Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004).
CONCLUSIONS: Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

Copyright 2006 Massachusetts Medical Society.
PMID 16914701  N Engl J Med. 2006 Aug 17;355(7):653-65. doi: 10.1056/N・・・
著者: D A Figueroa, E Mangini, M Amodio-Groton, B Vardianos, A Melchert, C Fana, W Wehbeh, C M Urban, S Segal-Maurer
雑誌名: Clin Infect Dis. 2009 Jul 15;49(2):177-80. doi: 10.1086/600039.
Abstract/Text BACKGROUND: There are limited safety data for high-dose and long-term daptomycin treatment (16mg/kg administered for >or=14 days). We present our experience in 61 patients.
METHODS: We performed a retrospective chart review for all patients treated with daptomycin at New York Hospital Queens (Flushing) from 1 January 2004 through 30 April 2007; patients were identified through a computerized hospital pharmacy database.
RESULTS: Sixty-one patients (29 male and 32 female patients; mean age, 66.6 years) received a mean dose of 8 mg/kg of daptomycin for a median of 25 days (range, 14-82 days). Twelve patients (with bone and skin and softtissue infections) did not have an identified microbiologic isolate. Gram-positive infections included bloodstream infection with or without infective endocarditis (n = 32), skin and soft-tissue infection (n = 14), bone and joint infection (n = 9), and intra-abdominal infection (n = 5), and unidentified infection (n = 1). Prosthetic devices were removed from 11 of 20 patients. Grade 1 adverse events occurred in 22 patients and did not lead to daptomycin discontinuation. Fifty-eight patients underwent creatine phosphokinase (CPK) analysis (34 patients had paired CPK analyses at the beginning of and during therapy, and 13 patients had random CPK analysis performed during treatment). Three patients had constitutional and/or musculoskeletal symptoms accompanying CPK levels 110 times upper limit of normal (grade 3). All occurred after 24 days of treatment and improved after daptomycin treatment was discontinued. Two of 3 patients were morbidly obese (body mass index grade III).
CONCLUSIONS: Daptomycin treatment was well tolerated at a mean dose of 8 mg/kg for a median duration of 25 days. The incidence of symptomatic CPK level elevation was within the range reported with lower doses of daptomycin and/or for shorter treatment durations.

PMID 19500039  Clin Infect Dis. 2009 Jul 15;49(2):177-80. doi: 10.1086・・・
著者: Marco Falcone, Alessandro Russo, Mario Venditti, Andrea Novelli, Manjunath P Pai
雑誌名: Clin Infect Dis. 2013 Dec;57(11):1568-76. doi: 10.1093/cid/cit582. Epub 2013 Sep 17.
Abstract/Text BACKGROUND: Higher daptomycin doses are advocated for select methicillin-resistant Staphylococcus aureus (MRSA)-related infections, but the probabilities of target attainment (PTA) and toxicity of these doses have not been characterized in critically ill patients.
METHODS: We evaluated the plasma pharmacokinetics (PK) and clinical outcomes of a cohort of critically ill patients treated with daptomycin 6-8 mg/kg/day for primarily Staphylococcus species-related infections. Daptomycin concentrations were measured intensively over the initial 96-hour dosing period. Data were modeled by population PK analyses, and Monte Carlo simulation was used to estimate the probabilities of effect and toxicity with standard and alternate dosing regimens.
RESULTS: Fifty patients with a mean (SD) age of 69.7 (12.2) years, weight 74.5 (20.3) kg, and creatinine clearance 56.8 (38.2) mL/minute were enrolled with measurements of 12 (2.2) daptomycin samples per patient. Significantly lower daptomycin exposures were observed despite comparable doses in a subset of patients (n = 13) with augmented clearance (CL). No covariates of CL were identified, but this subset was significantly more likely to be in severe sepsis or septic shock, have higher Sequential Organ Failure Assessment scores, and MRSA bacteremia. In-hospital mortality was significantly higher (30.7% vs 10.8%) in patients with augmented daptomycin CL. Use of an empiric fixed dose of 750 mg of daptomycin is predicted to achieve a comparable PTA with a lower probability of toxicity as compared to the use of 10 mg/kg in critically ill patients.
CONCLUSIONS: A reappraisal of current daptomycin dosing recommendations is needed to improve the PTA and reduce toxicity among critically ill patients.

PMID 24046298  Clin Infect Dis. 2013 Dec;57(11):1568-76. doi: 10.1093/・・・
著者: Alexander J Lepak, Karen Marchillo, Solen Pichereau, William A Craig, David R Andes
雑誌名: Antimicrob Agents Chemother. 2012 Nov;56(11):5916-22. doi: 10.1128/AAC.01303-12. Epub 2012 Sep 10.
Abstract/Text Tedizolid phosphate (TR-701) is a novel oxazolidinone prodrug (converted to the active form tedizolid [TR-700]) with potent Staphylococcus aureus activity. The current studies characterized and compared the in vivo pharmacokinetic/pharmacodynamic (PD) characteristics of TR-701/TR-700 and linezolid against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in the neutropenic murine pneumonia model. The pharmacokinetic properties of both drugs were linear over a dose range of 0.625 to 40 mg/kg of body weight. Protein binding was 30% for linezolid and 85% for TR-700. Mice were infected with one of 11 isolates of S. aureus, including MSSA and community- and hospital-acquired MRSA strains. Each drug was administered by oral-gastric gavage every 12 h (q12h). The dosing regimens ranged from 1.25 to 80 mg/kg/12 h for linezolid and 0.625 to 160 mg/kg/12 h for TR-701. At the start of therapy, mice had 6.24 ± 0.40 log(10) CFU/lungs, which increased to 7.92 ± 1.02 log(10) CFU/lungs in untreated animals over a 24-h period. A sigmoid maximum-effect (E(max)) model was used to determine the antimicrobial exposure associated with net stasis (static dose [SD]) and 1-log-unit reduction in organism relative to the burden at the start of therapy. The static dose pharmacodynamic targets for linezolid and TR-700 were nearly identical, at a free drug (non-protein-bound) area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) of 19 and 20, respectively. The 1-log-unit kill endpoints were also similar, at 46.1 for linezolid and 34.6 for TR-700. The exposure targets were also comparable for both MSSA and MRSA isolates. These dosing goals support further clinical trial examination of TR-701 in MSSA and MRSA pneumonia.

PMID 22964254  Antimicrob Agents Chemother. 2012 Nov;56(11):5916-22. d・・・
著者: Jeffrey M Rybak, Karrine Roberts
雑誌名: Infect Dis Ther. 2015 Feb 24;. doi: 10.1007/s40121-015-0060-3. Epub 2015 Feb 24.
Abstract/Text Treatment of multidrug-resistant Gram-positive infections continues to challenge clinicians as the emergence of new resistance mechanisms outpaces introduction of novel antimicrobial agents. Tedizolid phosphate is a next-generation oxazolidinone with activity against both methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp. Tedizolid has consistently shown potency advantages over linezolid against Gram-positive microorganisms including those with reduced susceptibility to linezolid. Of particular significance, minimum inhibitory concentrations of tedizolid appear to be largely unaffected by the chloramphenicol-florfenicol resistance (cfr) gene, which has been implicated in a number of published linezolid-resistant organism outbreaks. Tedizolid phosphate also has been found to have a favorable pharmacokinetic profile allowing for once-daily dosing in both oral and intravenous forms. Potency and pharmacokinetic advantages have allowed for lower total daily doses of tedizolid, compared to linezolid, being needed for clinical efficacy in the treatment of acute bacterial skin and skin structure infections (ABSSSI). The decreased total drug exposure produced may in part be responsible for a decrease in the observed adverse effects including thrombocytopenia. Tedizolid phosphate is currently indicated for the treatment of ABSSSI and under investigation for the treatment of nosocomial pneumonia. Although much of the role of tedizolid remains to be defined by expanding clinical experience, tedizolid is likely a welcomed addition to the mere handful of agents available for the treatment of multidrug-resistant Gram-positive infections.

PMID 25708156  Infect Dis Ther. 2015 Feb 24;. doi: 10.1007/s40121-015-・・・
著者: Andrew F Shorr, Thomas P Lodise, G Ralph Corey, Carisa De Anda, Edward Fang, Anita F Das, Philippe Prokocimer
雑誌名: Antimicrob Agents Chemother. 2015 Feb;59(2):864-71. doi: 10.1128/AAC.03688-14. Epub 2014 Nov 24.
Abstract/Text Tedizolid, a novel oxazolidinone with activity against a wide range of Gram-positive pathogens, was evaluated in two noninferiority phase 3 acute bacterial skin and skin structure infection trials. The data from individual trials showed its noninferior efficacy compared to that of linezolid and a favorable tolerability profile. To evaluate potential differences, the pooled data were analyzed. The patients received 200 mg of tedizolid once daily for 6 days or 600 mg of linezolid twice daily for 10 days. Efficacy was evaluated at 48 to 72 h (primary endpoint), on days 11 to 13 (end of therapy [EOT]), and 7 to 14 days after the EOT (posttherapy evaluation). Treatment-emergent adverse events and hematologic and clinical laboratory parameters were collected. The baseline characteristics were comparable between the treatment groups: 852/1,333 (64%) patients were from North America, and the majority of infections were caused by Staphylococcus aureus. Tedizolid was noninferior to linezolid (early clinical responses, 81.6% versus 79.4%, respectively). The early responses remained relatively consistent across various host/disease factors and severity measures. Nausea was the most frequently reported adverse event (tedizolid, 8.2%; linezolid, 12.2%; P=0.02), with onset occurring primarily during the first 6 days. Fewer tedizolid than linezolid patients had platelet counts of <150,000 cells/mm3 at the EOT (tedizolid, 4.9%; linezolid, 10.8%; P=0.0003) and during the postbaseline period through the last day of active drug visit (tedizolid, 6.4%; linezolid, 12.6%; P=0.0016). Efficacy was achieved with a 6-day once-daily course of therapy with the option of an intravenous/oral regimen, and fewer low platelet counts and gastrointestinal side effects were reported with tedizolid than with linezolid, all of which aligns well with antimicrobial stewardship principles. (These studies have been registered at ClinicalTrials.gov under registration no. NCT01170221 and NCT01421511.).

Copyright © 2015, American Society for Microbiology. All Rights Reserved.
PMID 25421472  Antimicrob Agents Chemother. 2015 Feb;59(2):864-71. doi・・・
著者: Jirong Yue, Bi Rong Dong, Ming Yang, Xiaomei Chen, Taixiang Wu, Guan J Liu
雑誌名: Cochrane Database Syst Rev. 2016 Jan 7;(1):CD008056. doi: 10.1002/14651858.CD008056.pub3. Epub 2016 Jan 7.
Abstract/Text BACKGROUND: The morbidity and treatment costs associated with skin and soft tissue infections (SSTIs) are high. Linezolid and vancomycin are antibiotics that are commonly used in treating skin and soft-tissue infections, specifically those infections due to methicillin-resistant Staphylococcus aureus (MRSA).
OBJECTIVES: To compare the effects and safety of linezolid and vancomycin for treating people with SSTIs.
SEARCH METHODS: For this first update of this review we conducted searches of the following databases: Cochrane Wounds Group Specialised Register (searched 24 March 2015; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also contacted manufacturers for details of unpublished and ongoing trials. We scrutinised citations within all obtained trials and major review articles to identify any additional trials.
SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing linezolid with vancomycin in the treatment of SSTIs.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias and extracted data. The primary outcomes were clinical cure, microbiological cure, and SSTI-related and treatment-related mortality. We performed subgroup analyses according to age, and whether the infection was due to MRSA.
MAIN RESULTS: No new trials were identified for this first update. We included nine RCTs (3144 participants). Linezolid was associated with a significantly better clinical (RR 1.09, 95% CI 1.03 to 1.16) and microbiological cure rate in adults (RR 1.08, 95% CI 1.01 to 1.16). For those infections due to MRSA, linezolid was significantly more effective than vancomycin in clinical (RR 1.09, 95% CI 1.03 to 1.17) and microbiological cure rates (RR 1.17, 95% CI 1.04 to 1.32). No RCT reported SSTI-related and treatment-related mortality. There was no significant difference in all-cause mortality between linezolid and vancomycin (RR 1.44, 95% CI 0.75 to 2.80). There were fewer incidents of red man syndrome (RR 0.04, 95% CI 0.01 to 0.29), pruritus (RR 0.36, 95% CI 0.17 to 0.75) and rash (RR 0.27, 95% CI 0.12 to 0.58) in the linezolid group compared with vancomycin, however, more people reported thrombocytopenia (RR 13.06, 95% CI 1.72 to 99.22), and nausea (RR 2.45, 95% CI 1.52 to 3.94) when treated with linezolid. It seems, from the available data, that length of stay in hospital was shorter for those in the linezolid group than the vancomycin group. The daily cost of outpatient therapy was less with oral linezolid than with intravenous vancomycin. Although inpatient treatment with linezolid cost more than inpatient treatment with vancomycin per day, the median length of hospital stay was three days shorter with linezolid. Thus, total hospital charges per patient were less with linezolid treatment than with vancomycin treatment.
AUTHORS' CONCLUSIONS: Linezolid seems to be more effective than vancomycin for treating people with SSTIs, including SSTIs caused by MRSA. The available evidence is at high risk of bias and is based on studies that were supported by the pharmaceutical company that makes linezolid. Further well-designed, independently-funded, RCTs are needed to confirm the available evidence.

PMID 26758498  Cochrane Database Syst Rev. 2016 Jan 7;(1):CD008056. do・・・
著者: Rachael McCool, Ian M Gould, Jacqui Eales, Teresa Barata, Mick Arber, Kelly Fleetwood, Julie Glanville, Teresa L Kauf
雑誌名: BMC Infect Dis. 2017 Jan 7;17(1):39. doi: 10.1186/s12879-016-2100-3. Epub 2017 Jan 7.
Abstract/Text BACKGROUND: Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA.
METHODS: Systematic review of 10 databases was undertaken to inform an NMA to estimate the relative effectiveness of tedizolid and established monotherapy comparators (ceftaroline, daptomycin, linezolid, teicoplanin, tigecycline, vancomycin) for treating MRSA-associated ABSSSI. Randomized controlled trials enrolling adults with ABSSSI or complicated skin and skin structure infections caused by suspected/documented MRSA were eligible for inclusion. Networks were developed based on similarity of study design, patient characteristics, outcome measures and available data. Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE) or test-of-cure assessment and treatment discontinuations resulting from adverse events (AEs). Bayesian NMA was conducted for each outcome using fixed-effects and random effects models.
RESULTS: Literature searches identified 3,618 records; 15 trials met the inclusion criteria and were considered suitable for NMA comparison. In fixed-effects models, tedizolid had higher odds of clinical response at EOT (odds ratio [OR], 1.7; credible interval, 1.0, 3.0) and PTE than vancomycin (OR, 1.6; credible interval, 1.1, 2.5). No differences in odds of clinical response at EOT or PTE were observed between tedizolid and other comparators. There was no evidence of a difference among treatments for discontinuation due to AEs. Results from random effects and fixed-effects models were generally consistent.
CONCLUSIONS: Tedizolid was superior to vancomycin for clinical response at EOT and PTE. There was no evidence of a difference between tedizolid and other comparators and no evidence of a difference between tedizolid and all comparators when evaluating discontinuation due to AEs. These findings suggest that tedizolid provides an alternative option for the management of serious skin infections caused by suspected or documented MRSA. This study is subject to the limitations inherent in all NMAs, and the results should be interpreted accordingly.

PMID 28061827  BMC Infect Dis. 2017 Jan 7;17(1):39. doi: 10.1186/s1287・・・
著者: Steven D Burdette, Robin Trotman
雑誌名: Clin Infect Dis. 2015 Oct 15;61(8):1315-21. doi: 10.1093/cid/civ501. Epub 2015 Jun 23.
Abstract/Text Tedizolid phosphate is the second commercially available oxazolidinone antibiotic, although the first one in class that is dosed once daily. It is a prodrug that is rapidly converted to the active compound tedizolid. Tedizolid has activity against a wide range of gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. It is approved to treat acute bacterial skin and skin structure infections (ABSSSIs). In 2 randomized controlled phase 3 trials, 6 days of tedizolid (200 mg once daily) has been proven to be noninferior to 10 days of linezolid (600 mg twice daily). These 2 ABSSSI studies have positioned tedizolid among the growing armamentarium of newer, novel, anti-gram-positive agents. Tedizolid appears to differ from linezolid in the incidence of gastrointestinal and hematologic side effects and appears to lack drug interactions with selective serotonin reuptake inhibitors. Conditions other than ABSSSI are currently being evaluated in clinical studies.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID 26105167  Clin Infect Dis. 2015 Oct 15;61(8):1315-21. doi: 10.109・・・
著者: Hiroshige Mikamo, Yoshio Takesue, Yuji Iwamoto, Takahiko Tanigawa, Masaharu Kato, Yoko Tanimura, Shigeru Kohno
雑誌名: J Infect Chemother. 2018 Jun;24(6):434-442. doi: 10.1016/j.jiac.2018.01.010. Epub 2018 Mar 9.
Abstract/Text The objective of this open-label, randomised (i.e. 2:1 ratio), Phase 3 study was to compare the efficacy and safety of tedizolid phosphate 200 mg, once-daily treatment with that of linezolid 600 mg, twice-daily treatment for 7-14 days in Japanese adult patients (N = 125) with skin and soft tissue infections (SSTIs) and/or for 7-21 days for those with SSTI-related bacteraemia, caused by confirmed or highly suspected methicillin-resistant Staphylococcus aureus (MRSA). Primary outcome was clinical cure rate at test-of-cure (TOC, in SSTI: 7-14 days, in bacteraemia: 4-6 weeks after end-of-therapy [EOT]) time point in the microbiologically evaluable MRSA (ME-MRSA) population (N = 39). Secondary endpoints were clinical and microbiological response rates at EOT. Safety parameters were evaluated in the safety analysis population up to follow up. Data analysis was descriptive in nature. Baseline characteristics of patients were similar between treatment groups. At TOC in the ME-MRSA population, clinical cure rate was similar in tedizolid phosphate (92.6%) and linezolid (88.9%) groups. At EOT, clinical cure (tedizolid phosphate: 93.1%, linezolid: 90.0%) and microbiological success (tedizolid phosphate: 93.1%, linezolid: 100.0%) rates were similar in the ME-MRSA population. Both treatments were well tolerated; overall treatment-emergent adverse events (TEAEs) in tedizolid phosphate (79.5%) and linezolid (75.6%) treatment groups were similar. Drug-related TEAEs were numerically lower with tedizolid phosphate versus linezolid (30.1%; 39.0%, respectively), as well as gastrointestinal (21.7%; 26.8%) and myelosuppression-related (2.4%; 22.0%) TEAEs. One death occurred in the linezolid group. Tedizolid phosphate may be an appropriate antibiotic for the treatment of SSTIs in Japanese adult patients. International clinical trial registration number: NCT01967225. Japanese clinical trial registration number: JapicCTI-132308.

Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 29530544  J Infect Chemother. 2018 Jun;24(6):434-442. doi: 10.101・・・
著者: Mical Paul, Jihad Bishara, Dafna Yahav, Elad Goldberg, Ami Neuberger, Nesrin Ghanem-Zoubi, Yaakov Dickstein, William Nseir, Michael Dan, Leonard Leibovici
雑誌名: BMJ. 2015 May 14;350:h2219. Epub 2015 May 14.
Abstract/Text OBJECTIVE: To show non-inferiority of trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant Staphylococcus aureus (MRSA).
DESIGN: Parallel, open label, randomised controlled trial.
SETTING: Four acute care hospitals in Israel.
PARTICIPANTS: Adults with severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and vancomycin. Patients with left sided endocarditis, meningitis, chronic haemodialysis, and prolonged neutropenia were excluded.
INTERVENTIONS: Trimethoprim-sulfamethoxazole 320 mg/1600 mg twice daily versus vancomycin 1 g twice daily for a minimum of seven days and then by indication.
MAIN OUTCOME MEASURES: The primary efficacy outcome was treatment failure assessed at day 7, consisting of death, persistence of haemodynamic instability or fever, stable or worsening Sequential Organ Failure Assessment score, and persistence of bacteraemia. The primary safety outcome was all cause mortality at day 30. Non-inferiority was defined by a difference of less than 15% for treatment failure.
RESULTS: 252 patients were included in the trial, of whom 91 (36%) had bacteraemia. No significant difference in treatment failure was seen for trimethoprim-sulfamethoxazole (51/135, 38%) versus vancomycin (32/117, 27%)-risk ratio 1.38 (95% confidence interval 0.96 to 1.99). However, trimethoprim-sulfamethoxazole did not meet the non-inferiority criterion-absolute difference 10.4% (95% confidence interval -1.2% to 21.5%). For patients with bacteraemia, the risk ratio was 1.40 (0.91 to 2.16). In a multivariable logistic regression analysis, trimethoprim-sulfamethoxazole was significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93).
CONCLUSIONS: High dose trimethoprim-sulfamethoxazole did not achieve non-inferiority to vancomycin in the treatment of severe MRSA infections. The difference was particularly marked for patients with bacteraemia. Trial registration Clinical trials NCT00427076.

© Paul et al 2015.
PMID 25977146  BMJ. 2015 May 14;350:h2219. Epub 2015 May 14.
著者: Sara E Cosgrove, Vance G Fowler
雑誌名: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S386-93. doi: 10.1086/533595.
Abstract/Text Staphylococcus aureus bacteremia and endocarditis are serious infections that demand prompt clinical attention to ensure good outcomes. Of foremost importance is identifying and managing the source of infection and any associated complications. Evaluation for the presence of cardiac involvement is essential because inadequately managed S. aureus endocarditis is life threatening. Thus, physicians must aggressively negotiate treatment paths, considering whether the S. aureus bacteremia is complicated, whether foreign sources of infection should be removed or replaced, and whether surgical intervention is necessary. Selection of an antibiotic treatment is also an essential factor for optimal management. The increasing prevalence of methicillin-resistant S. aureus (MRSA) infections has created a tremendous demand for effective and safe antimicrobial agents other than the historic anti-MRSA agent vancomycin.

PMID 18462094  Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S386-93. doi: 10・・・
著者: Vance G Fowler, Maren K Olsen, G Ralph Corey, Christopher W Woods, Christopher H Cabell, L Barth Reller, Allen C Cheng, Tara Dudley, Eugene Z Oddone
雑誌名: Arch Intern Med. 2003 Sep 22;163(17):2066-72. doi: 10.1001/archinte.163.17.2066.
Abstract/Text BACKGROUND: Complications of Staphylococcus aureus bacteremia (SAB) are often difficult to identify. The ability to accurately predict the likelihood of these complications would impact patient management. This investigation sought to define readily available clinical characteristics that could help identify patients at risk for complicated SAB.
METHODS: A prospective, observational cohort study was conducted from September 1994 through December 1999. Patients were followed up for 12 weeks after the initial positive blood culture result. The primary end point was complicated SAB (attributable mortality, complicated infection, embolic stroke, or recurrent S aureus infection during the 12-week follow-up period). The predictive model was validated using bootstrap resampling.
RESULTS: Complicated SAB was present in 43% of 724 consecutive adult hospitalized patients identified during the study period. The full predictive model had a high discriminative ability (bootstrap-corrected c index, 0.78). The strongest predictor of complicated SAB was a positive follow-up blood culture result at 48 to 96 hours. A scoring system based on the presence or absence of 4 risk factors (community acquisition, skin examination findings suggesting acute systemic infection, persistent fever at 72 hours, and positive follow-up blood culture results at 48-96 hours) accurately identified complicated SAB (bootstrap-corrected c index, 0.76).
CONCLUSION: Readily available clinical variables can help identify patients at risk for complicated SAB.

PMID 14504120  Arch Intern Med. 2003 Sep 22;163(17):2066-72. doi: 10.1・・・
著者: S Lautenschlager, C Herzog, W Zimmerli
雑誌名: Clin Infect Dis. 1993 Apr;16(4):567-73.
Abstract/Text In a retrospective survey of patients hospitalized in the University Hospital of Basel, Switzerland, the course and outcome of 281 cases of true bacteremia due to Staphylococcus aureus over a 7-year period were analyzed. The main purpose was to evaluate different case definitions. In 78% of cases the source of bacteremia was obvious; vascular access sites (27%) and wounds (10%) were the most common sources. Metastasizing foci were more common in cases of primary vs. secondary bacteremia (P < .001). The incidence of endocarditis was higher in cases in which no portal of entry was defined (P < .03). The overall mortality rate was high at 34% partly because of inappropriate initial antibiotic therapy. With the introduction of an infectious disease service at the hospital, the fraction of misjudged results of blood culture diminished 2.5-fold. Among the differently defined cases, the mortality rate was significantly higher for cases of complicated vs. uncomplicated bacteremia (P < .01), for cases of primary vs. secondary bacteremia (P = .05), and for patients with endocarditis or other secondary foci (P < .001). Since only one methicillin-resistant strain was isolated, multiresistant staphylococci were not a problem in the hospital. Different case definitions allowed the detection of patients at increased risk for complications and death. In the treatment of sepsis with no evident focus, initial antimicrobial therapy should include the use of agents with antistaphylococcal activity.

PMID 8513067  Clin Infect Dis. 1993 Apr;16(4):567-73.
著者: H Ringberg, A Thorén, B Lilja
雑誌名: Infection. 2000 May-Jun;28(3):132-6.
Abstract/Text Improvement in the high mortality from Staphylococcus aureus septicemia must address the individualized treatment (surgery and/or prolonged antibiotic treatment) of metastatic complications. The aim of this study was to evaluate the results of a comprehensive diagnostic monitoring for metastatic complications in S. aureus septicemia. 68 consecutive patients with S. aureus septicemia were prospectively followed. The performance rate and results of chest X-ray, echocardiography, bone scintigraphy and leukocyte scintigraphy are described. Metastatic complications were found in 53% of the 68 patients, endocarditis in 26%. Positive findings resulted in surgical intervention in 23 patients. The total mortality defined as all deaths within 12 weeks was 24%; 81% of the deceased were > or = 60 years of age. Non-endocarditis patients with peripheral septic metastases had good prognosis. An active monitoring for metastatic complications in S. aureus septicemia is a necessary prerequisite for optimizing treatment and to improve survival rate.

PMID 10879635  Infection. 2000 May-Jun;28(3):132-6.
著者: Patrick F Smith, Brent M Booker, Abayomi B Ogundele, Pamela Kelchin
雑誌名: Diagn Microbiol Infect Dis. 2005 Jul;52(3):255-9. doi: 10.1016/j.diagmicrobio.2005.02.015.
Abstract/Text Our objective was to evaluate and compare the in vitro activity of daptomycin, linezolid, and quinupristin/dalfopristin against clinical bloodstream isolates of Gram-positive pathogens from a large cancer center in the Northeastern United States. Minimum inhibitory concentrations (MICs) were determined for daptomycin, quinupristin/dalfopristin, and linezolid against 258 isolates; bactericidal activity was evaluated using time-kill experiments against 14 representative pathogens. Vancomycin-resistant enterococci represented the largest proportion of bacteria tested (32% of the isolates), followed by methicillin-resistant coagulase-negative staphylococci (23%), and vancomycin sensitive enterococci (14%). Against staphylococci, the MIC90 was 1 microg/mL for both daptomycin and quinupristin/dalfopristin and 4 microg/mL for linezolid. Against enterococci, the MIC90 for both daptomycin and linezolid was 4 microg/mL and was 16 microg/mL for quinupristin/dalfopristin. The quinupristin/dalfopristin MIC90 for Enterococcus faecium was 2 microg/mL. Two enterococci were linezolid resistant and remained susceptible to daptomycin. In vitro time-kill studies found daptomycin to be rapidly bactericidal against the majority of organisms tested, killing 99.9% of bacteria within 6 h. Quinupristin/dalfopristin was bactericidal against staphylococci and bacteriostatic against most enterococci. Linezolid was bacteriostatic against all organisms evaluated. Daptomycin, quinupristin/dalfopristin, and linezolid each demonstrated in vitro activity against this collection of organisms. Future clinical studies to evaluate a potential role for these agents in the management of infections in cancer patients, including the treatment of febrile neutropenia, appear warranted.

PMID 15935606  Diagn Microbiol Infect Dis. 2005 Jul;52(3):255-9. doi: ・・・
著者: Raymond Cha, William J Brown, Michael J Rybak
雑誌名: Antimicrob Agents Chemother. 2003 Dec;47(12):3960-3.
Abstract/Text In search of treatment alternatives against vancomycin-resistant S. aureus (VRSA), an in vitro pharmacodynamic model with simulated endocardial vegetations incorporating protein and a high inoculum was used to simulate daptomycin, linezolid, quinupristin-dalfopristin, and vancomycin against the Michigan VRSA strain. Daptomycin and quinupristin-dalfopristin exhibited the greatest bacterial reductions, and all tested agents except vancomycin exhibited bactericidal activity against the VRSA.

PMID 14638509  Antimicrob Agents Chemother. 2003 Dec;47(12):3960-3.
著者: M Sharma, K Riederer, P Chase, R Khatib
雑誌名: Eur J Clin Microbiol Infect Dis. 2008 Jun;27(6):433-7. doi: 10.1007/s10096-007-0455-5. Epub 2008 Jan 23.
Abstract/Text Daptomycin is bactericidal against Staphylococcus aureus, with susceptibility defined as a minimal inhibitory concentration (MIC) < or =1 microg/ml. Higher MIC developed in a few cases during therapy. The frequency of MIC rise in persistent bacteremia is unknown. We evaluated all patients with S. aureus bacteremia (SAB) treated with daptomycin (> or =2 days) from 1 April 2004 to 30 October 2006. All patients with post-daptomycin-exposure saved isolates were studied. Daptomycin susceptibility was determined (in duplicate) on all pre- and post-daptomycin-exposure isolates by the broth (Mueller-Hinton) microdilution method. Among 74 treatment courses in 67 patients, 18 were for SAB. Ten had persistent bacteremia (median = 11 days; range = 1-21) and post-daptomycin-exposure saved isolates. The patient age was 29-84 years (median = 57.5 years). Intravascular catheter was the most common source (50%). Most patients (90%) failed therapy prior to starting daptomycin. The initial daptomycin dose was 4 mg/kg in four (40%) cases. The pre-exposure MIC was 0.125-0.5 microg/ml. The post-exposure MIC increased in four cases and was elevated in two cases (60%), to 2 microg/ml in five and 4 microg/ml in one. MIC rise was noted within 5-15 days of exposure and persisted up to 247 days after stopping daptomycin. Pulse-field gel electrophoresis (PFGE) band pattern of isolates with increased MIC revealed 1-3-band differences, implying genetic relatedness. All patients with non-susceptible isolates relapsed or failed therapy. These findings illustrate that daptomycin susceptibility often decreases during the treatment of persistent SAB. Therefore, susceptibility should be closely monitored during therapy.

PMID 18214559  Eur J Clin Microbiol Infect Dis. 2008 Jun;27(6):433-7. ・・・
著者: Dennis L Stevens, Alan L Bisno, Henry F Chambers, E Patchen Dellinger, Ellie J C Goldstein, Sherwood L Gorbach, Jan V Hirschmann, Sheldon L Kaplan, Jose G Montoya, James C Wade
雑誌名: Clin Infect Dis. 2014 Jul 15;59(2):147-59. doi: 10.1093/cid/ciu296. Epub 2014 Jun 18.
Abstract/Text A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID 24947530  Clin Infect Dis. 2014 Jul 15;59(2):147-59. doi: 10.1093・・・
著者: Yi Mu, Jonathan R Edwards, Teresa C Horan, Sandra I Berrios-Torres, Scott K Fridkin
雑誌名: Infect Control Hosp Epidemiol. 2011 Oct;32(10):970-86. doi: 10.1086/662016. Epub 2011 Sep 1.
Abstract/Text BACKGROUND: The National Healthcare Safety Network (NHSN) has provided simple risk adjustment of surgical site infection (SSI) rates to participating hospitals to facilitate quality improvement activities; improved risk models were developed and evaluated.
METHODS: Data reported to the NHSN for all operative procedures performed from January 1, 2006, through December 31, 2008, were analyzed. Only SSIs related to the primary incision site were included. A common set of patient- and hospital-specific variables were evaluated as potential SSI risk factors by univariate analysis. Some ific variables were available for inclusion. Stepwise logistic regression was used to develop the specific risk models by procedure category. Bootstrap resampling was used to validate the models, and the c-index was used to compare the predictive power of new procedure-specific risk models with that of the models with the NHSN risk index as the only variable (NHSN risk index model).
RESULTS: From January 1, 2006, through December 31, 2008, 847 hospitals in 43 states reported a total of 849,659 procedures and 16,147 primary incisional SSIs (risk, 1.90%) among 39 operative procedure categories. Overall, the median c-index of the new procedure-specific risk was greater (0.67 [range, 0.59-0.85]) than the median c-index of the NHSN risk index models (0.60 [range, 0.51-0.77]); for 33 of 39 procedures, the new procedure-specific models yielded a higher c-index than did the NHSN risk index models.
CONCLUSIONS: A set of new risk models developed using existing data elements collected through the NHSN improves predictive performance, compared with the traditional NHSN risk index stratification.

PMID 21931247  Infect Control Hosp Epidemiol. 2011 Oct;32(10):970-86. ・・・
著者: Kurinchi Selvan Gurusamy, Rahul Koti, Clare D Toon, Peter Wilson, Brian R Davidson
雑誌名: Cochrane Database Syst Rev. 2013 Aug 20;(8):CD009726. doi: 10.1002/14651858.CD009726.pub2. Epub 2013 Aug 20.
Abstract/Text BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection after surgery is usually rare, but incidence can be up to 33% in certain types of surgery. Postoperative MRSA infection can occur as surgical site infections (SSI), chest infections, or bloodstream infections (bacteraemia). The incidence of MRSA SSIs varies from 1% to 33% depending upon the type of surgery performed and the carrier status of the individuals concerned. The optimal antibiotic regimen for the treatment of MRSA in surgical wounds is not known.
OBJECTIVES: To compare the benefits and harms of various antibiotic treatments in people with established surgical site infections (SSIs) caused by MRSA .
SEARCH METHODS: In February 2013 we searched the following databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE); NHS Economic Evaluation Database; Health Technology Assessment (HTA) Database; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL.
SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing one antibiotic regimen with another antibiotic regimen for the treatment of SSIs due to MRSA. All RCTs irrespective of language, publication status, publication year, or sample size were included in the analysis.
DATA COLLECTION AND ANALYSIS: Two review authors independently decided on inclusion and exclusion of trials, and extracted data. We planned to calculate the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both a fixed-effect and a random-effects model. We performed intention-to-treat analysis whenever possible.
MAIN RESULTS: We included one trial involving 59 people hospitalised because of MRSA SSIs. Thirty participants were randomised to linezolid (600 mg either intravenously or orally every 12 hours for seven to 14 days) and 29 to vancomycin (1 g intravenously every 12 hours for seven to 14 days). The type of surgical procedures that were performed were not reported. The trial reported one outcome, which was the eradication of MRSA. The proportion of people in whom MRSA was eradicated was statistically significantly higher in the linezolid group than in the vancomycin group (RR 1.80; 95% CI 1.20 to 2.68).
AUTHORS' CONCLUSIONS: There is currently no evidence to recommend any specific antibiotic in the treatment of MRSA SSIs. Linezolid is superior to vancomycin in the eradication of MRSA SSIs on the basis of evidence from one small trial that was at high risk of bias, but the overall clinical implications of using linezolid instead of vancomycin are not known. Further well-designed randomised clinical trials are necessary in this area.

PMID 23963687  Cochrane Database Syst Rev. 2013 Aug 20;(8):CD009726. d・・・
著者: Kalpana Gupta, Judith Strymish, Youmna Abi-Haidar, Sandra A Williams, Kamal M F Itani
雑誌名: Infect Control Hosp Epidemiol. 2011 Aug;32(8):791-6. doi: 10.1086/660362.
Abstract/Text OBJECTIVES: To determine whether preoperative nasal methicillin-resistant Staphylococcus aureus (MRSA) carriage is a significant predictor of postoperative infections, after accounting for surgical infection risk and surgical prophylaxis.
DESIGN: Retrospective cohort study.
PATIENTS: Veterans Affairs (VA) Boston patients who had nasal MRSA polymerase chain reaction screening performed in the 31 days before clean or clean contaminated surgery in 2008-2009.
METHODS: Postoperative MRSA clinical cultures and infections, total surgical site infections (SSIs), and surgical prophylaxis data were abstracted from administrative databases. MRSA infections were confirmed via chart review. Multivariate analysis of risk factors for each outcome was conducted using Poisson regression. SSI risk index was calculated for a subset of 1,551 patients assessed by the VA National Surgical Quality Improvement Program.
RESULTS: Among 4,238 eligible patients, 279 (6.6%) were positive for preoperative nasal MRSA. Postoperative MRSA clinical cultures and infections, including MRSA SSIs, were each significantly increased in patients with preoperative nasal MRSA. After adjustment for surgery type, vancomycin prophylaxis, chlorhexidine/alcohol surgical skin preparation, and SSI risk index, preoperative nasal MRSA remained significantly associated with postoperative MRSA cultures (relative risk [RR], 8.81; 95% confidence interval [CI], 3.01-25.82) and infections (RR, 8.46; 95% CI, 1.70-42.04). Vancomycin prophylaxis was associated with an increased risk of total SSI in those negative for nasal MRSA (RR, 4.34; 95% CI, 2.19-8.57) but not in patients positive for nasal MRSA.
CONCLUSIONS: In our population, preoperative nasal MRSA colonization was independently associated with MRSA clinical cultures and infections in the postoperative period. Vancomycin prophylaxis increased the risk of total SSI in nasal MRSA-negative patients.

PMID 21768763  Infect Control Hosp Epidemiol. 2011 Aug;32(8):791-6. do・・・
著者: Duncan Chambers, Gillian Worthy, Lindsey Myers, Helen Weatherly, Rachel Elliott, Neil Hawkins, Mark Sculpher, Alison Eastwood
雑誌名: Surg Infect (Larchmt). 2010 Oct;11(5):455-62. doi: 10.1089/sur.2009.055.
Abstract/Text BACKGROUND: Patients receive prophylactic antibiotics against surgical site infections (SSIs) before or during many procedures. Glycopeptide antibiotics are effective against most strains of methicillin-resistant Staphylococcus aureus (MRSA), but their wider use risks increasing resistance. Our objective was to review the evidence for clinical effectiveness that might help to determine whether there is a threshold of MRSA prevalence at which switching from non-glycopeptide to glycopeptide antibiotic prophylaxis might be justified.
METHODS: We performed a systematic review of randomized trials comparing a glycopeptide with an alternative antibiotic regimen for SSI prophylaxis in adults undergoing clean or clean-contaminated surgical procedures. The evidence was used to inform development of a decision-analytic model. We subsequently updated the review to May 2008.
RESULTS: Fourteen studies were identified that provided evidence concerning clinical effectiveness. The studies were too heterogeneous clinically for meta-analysis. Only one of 12 trials found that glycopeptides reduced SSIs significantly at 30 days compared with non-glycopeptide antibiotics. Of the two trials that reported on MRSA infection, neither found a significant difference between glycopeptide and comparator drugs.
CONCLUSIONS: This systematic review did not find any evidence to support the use of glycopeptides in preference to other antibiotics for the prevention of MRSA infections and SSIs. The limitations of the evidence make it difficult to identify a threshold at which a switch from non-glycopeptide to glycopeptide prophylaxis should be recommended. Given the difficulties of addressing this issue through randomized trials, further research should focus on hospital infection control policies, MRSA screening, and the isolation and treatment of anyone infected with MRSA prior to surgery.

PMID 20815758  Surg Infect (Larchmt). 2010 Oct;11(5):455-62. doi: 10.1・・・
著者: Tonya Crawford, Keith A Rodvold, Joseph S Solomkin
雑誌名: Clin Infect Dis. 2012 May;54(10):1474-9. doi: 10.1093/cid/cis027. Epub 2012 Feb 10.
Abstract/Text The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has resulted in a reevaluation of the role of vancomycin for surgical prophylaxis. Two systematic reviews of randomized control studies have concluded that cephalosporins are as effective as vancomycin for the prevention of surgical site infections (SSIs). However, most of these studies were conducted more than 10 years ago and cannot be generalized to the current rates of MRSA. Several time-series analyses have recently evaluated the effectiveness of vancomycin for surgical prophylaxis in institutions with a high prevalence of MRSA. Decision analysis models have also been used to estimate thresholds of MRSA prevalence for which vancomycin would minimize the incidence and cost of SSIs. Combination therapy and the emergence of resistant pathogens following vancomycin prophylaxis are reviewed. Vancomycin is not recommended for routine use in surgical prophylaxis but may be considered as a component of a MRSA prevention bundle for SSIs in selective circumstances.

PMID 22328468  Clin Infect Dis. 2012 May;54(10):1474-9. doi: 10.1093/c・・・
著者: John Weigelt, Haytham M A Kaafarani, Kamal M F Itani, Robert N Swanson
雑誌名: Am J Surg. 2004 Dec;188(6):760-6. doi: 10.1016/j.amjsurg.2004.08.045.
Abstract/Text BACKGROUND: The purpose of this analysis was to compare the efficacy of linezolid versus vancomycin in patients with suspected or proven gram-positive methicillin-resistant Staphylococcus aureus (MRSA) surgical-site infections.
METHODS: An open-label, randomized, comparator-controlled, multicenter, multinational study was conducted in hospitalized patients. Patients were randomized 1:1 to receive linezolid 600 mg (intravenous [IV] or oral) every 12 hours (n = 66) or vancomycin 1 g every 12 hours IV (n = 69) for 7 to 21 days. Patients were assessed at the test-of-cure (TOC) visit, 7 days after completing therapy.
RESULTS: Clinical success at TOC was documented in similar proportions of patients treated with linezolid or vancomycin. Of those with MRSA isolated, significantly more patients who received linezolid compared with those who received vancomycin were microbiologically cured (87% vs 48%, respectively; 95% confidence interval 16.51 to 60.27; P = 0.0022).
CONCLUSION: Intravenous or oral linezolid was well tolerated and superior to vancomycin in treating patients with MRSA-infected surgical-site infections.

PMID 15619496  Am J Surg. 2004 Dec;188(6):760-6. doi: 10.1016/j.amjsur・・・
著者: Leonard A Mermel, Michael Allon, Emilio Bouza, Donald E Craven, Patricia Flynn, Naomi P O'Grady, Issam I Raad, Bart J A Rijnders, Robert J Sherertz, David K Warren
雑誌名: Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/599376.
Abstract/Text
PMID 19489710  Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/59・・・
著者: Sara E Cosgrove, George Sakoulas, Eli N Perencevich, Mitchell J Schwaber, Adolf W Karchmer, Yehuda Carmeli
雑誌名: Clin Infect Dis. 2003 Jan 1;36(1):53-9. doi: 10.1086/345476. Epub 2002 Dec 13.
Abstract/Text A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia. A search of the MEDLINE database for studies published during the period of 1 January 1980 through 31 December 2000 and a bibliographic review identified English-language studies of S. aureus bacteremia. Studies were included if they contained the numbers of and mortality rates for patients with methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) bacteremia. Data were extracted on demographic characteristics of the patients, adjustment for severity and comorbid illness, source of bacteremia, and crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality. When the results were pooled with a random-effects model, a significant increase in mortality associated with MRSA bacteremia was evident (OR, 1.93; 95% CI, 1.54-2.42; P<.001); significant heterogeneity was present. We explored the reasons for heterogeneity by means of subgroup analyses. MRSA bacteremia is associated with significantly higher mortality rate than is MSSA bacteremia.

PMID 12491202  Clin Infect Dis. 2003 Jan 1;36(1):53-9. doi: 10.1086/34・・・
著者: Vance G Fowler, Anita Justice, Catrin Moore, Daniel K Benjamin, Christopher W Woods, Steven Campbell, L Barth Reller, G Ralph Corey, Nicholas P J Day, Sharon J Peacock
雑誌名: Clin Infect Dis. 2005 Mar 1;40(5):695-703. doi: 10.1086/427806. Epub 2005 Feb 4.
Abstract/Text BACKGROUND: The role of both host and pathogen characteristics in hematogenous seeding following Staphylococcus aureus bacteremia is incompletely understood.
METHODS: Consecutive patients with intravascular catheter-associated Staphylococcus aureus bacteremia were prospectively recruited over a 91-month period. The corresponding bloodstream isolates were examined for the presence of 35 putative virulence determinants. Patient and bacterial characteristics associated with the development of hematogenous complications (HCs) (i.e., septic arthritis, vertebral osteomyelitis, or endocarditis) were defined.
RESULTS: HC occurred in 42 (13%) of 324 patients. Patient characteristics at diagnosis that were associated with HC included community onset (relative risk [RR], 2.25; 95% confidence interval [CI], 1.24-4.07; P=.007), increased symptom duration (odds ratio for each day, 1.14; 95% CI, 1.06-1.2; P<.001), presence of a long-term intravascular catheter or noncatheter prosthesis (RR, 4.02; 95% CI, 1.74-9.27; P<.001), hemodialysis dependence (RR, 3.84; 95% CI, 2.08-7.10; P<.001), and higher APACHE II score (P=.02). Bacterial characteristics included sea (RR, 2.03; 95% CI, 1.16-3.55; P=.011) and methicillin-resistant S. aureus (MRSA) (RR, 2.09; 95% CI, 1.19-3.67; P=.015). Subsequent failure to remove a catheter was also associated with HC (RR, 2.28; 95% CI, 1.22-4.27; P=.011). On multivariable analysis, symptom duration, hemodialysis dependence, presence of a long-term intravascular catheter or a noncatheter device, and infection with MRSA remained significantly associated with HC.
CONCLUSIONS: This investigation identifies 4 host- and pathogen-related risk factors for hematogenous bacterial seeding and reaffirms the importance of prompt catheter removal.

PMID 15714415  Clin Infect Dis. 2005 Mar 1;40(5):695-703. doi: 10.1086・・・
著者: Jane D Siegel, Emily Rhinehart, Marguerite Jackson, Linda Chiarello, Health Care Infection Control Practices Advisory Committee
雑誌名: Am J Infect Control. 2007 Dec;35(10 Suppl 2):S65-164. doi: 10.1016/j.ajic.2007.10.007.
Abstract/Text
PMID 18068815  Am J Infect Control. 2007 Dec;35(10 Suppl 2):S65-164. d・・・
著者: David Bracco, Marc-Jacques Dubois, Redouane Bouali, Philippe Eggimann
雑誌名: Intensive Care Med. 2007 May;33(5):836-40. doi: 10.1007/s00134-007-0559-5. Epub 2007 Mar 9.
Abstract/Text OBJECTIVE: Nosocomial infections remain a major problem in intensive care units. Several authorities have recommended housing patients in single rooms to prevent cross-transmission of potential pathogens, but this issue is currently debated. The aim of the present study was to compare the rate of nosocomial cross-contamination between patients hosted in single rooms versus bay rooms.
DESIGN: Prospective observational data acquisition over 2.5 years.
SETTING: A 14-bed medico-surgical ICU, composed of six single-bed rooms plus a six-bed and a two-bed bay room served by the same staff.
PATIENTS AND PARTICIPANTS: All patients admitted from 1 July 2002 to 31 December 2004.
INTERVENTIONS: None.
MEASUREMENTS AND RESULTS: Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in admitted patients was 1.1% and acquisition rate 2.4%. The incidence density of MRSA acquisition was 4.1 [95% CI 2.7-6.3]/1,000 patient-days in bay rooms versus 1.3 [0.5-3.4]/1,000 patient-days in single rooms (p<0.001). Pseudomonas spp. acquisition rate was 3.9 [2.5-6.1]/1,000 patient-days in bay rooms versus 0.7 [0.2-2.4]/1,000 patient-days in single rooms (p<0.001), and Candida spp. colonization was 38.4 [33.3-44.1]/1,000 patient-days in bay rooms versus 13.8 [10.2-18.6]/1,000 patient-days (p<0.001). By multivariate analysis, the relative risk of MRSA, Pseudomonas aeruginosa and Candida spp. acquisition in single rooms or cubicles versus bay rooms was 0.65, 0.61 and 0.75 respectively.
CONCLUSIONS: These data suggest that in an institution where MRSA is not hyperendemic, infection control measures may be more effective to prevent cross-transmission of microorganisms in patients housed in single rooms.

PMID 17347828  Intensive Care Med. 2007 May;33(5):836-40. doi: 10.1007・・・
著者: Vaira Leimane, Vija Riekstina, Timothy H Holtz, Evija Zarovska, Vija Skripconoka, Lorna E Thorpe, Kayla F Laserson, Charles D Wells
雑誌名: Lancet. 2005 Jan 22-28;365(9456):318-26. doi: 10.1016/S0140-6736(05)17786-1.
Abstract/Text BACKGROUND: Latvia has one of the highest rates of multidrug-resistant tuberculosis (MDRTB). Our aim was to assess treatment outcomes for the first full cohort of MDRTB patients treated under Latvia's DOTS-Plus strategy following WHO guidelines.
METHODS: We retrospectively reviewed all civilian patients who began treatment with individualised treatment regimens for pulmonary MDRTB in Latvia between Jan 1, and Dec 31, 2000. We applied treatment outcome definitions for MDRTB, developed by an international expert consensus group, and assessed treatment effectiveness and risk factors associated with poor outcome.
FINDINGS: Of the 204 patients assessed, 55 (27%) had been newly diagnosed with MDRTB, and 149 (73%) had earlier been treated with first-line or second-line drugs for this disease. Assessment of treatment outcomes showed that 135 (66%) patients were cured or completed therapy, 14 (7%) died, 26 (13%) defaulted, and treatment failed in 29 (14%). Of the 178 adherent patients, 135 (76%) achieved cure or treatment completion. In a multivariate Cox proportional-hazards model of these patients, independent predictors of poor outcome (death and treatment failure) included having previously received treatment for MDRTB (hazard ratio 5.7, 95% CI 1.9-16.6), the use of five or fewer drugs for 3 months or more (3.2, 1.1-9.6), resistance to ofloxacin (2.6, 1.2-5.4), and body-mass index less than 18.5 at start of treatment (2.3, 1.1-4.9).
INTERPRETATION: The DOTS-Plus strategy of identifying and treating patients with MDRTB can be effectively implemented on a nationwide scale in a setting of limited resources.

PMID 15664227  Lancet. 2005 Jan 22-28;365(9456):318-26. doi: 10.1016/S・・・
著者: Alexandre R Marra, Michael B Edmond, Marin L Schweizer, Grace W Ryan, Daniel J Diekema
雑誌名: Am J Infect Control. 2017 Oct 11;. doi: 10.1016/j.ajic.2017.08.031. Epub 2017 Oct 11.
Abstract/Text BACKGROUND: Several single-center studies have suggested that eliminating contact precautions (CPs) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) control in nonoutbreak settings has no impact on infection rates. We performed a systematic literature review and meta-analysis on the impact of discontinuing contact precautions in the acute care setting.
METHODS: We searched PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Embase through December 2016 for studies evaluating discontinuation of contact precautions for multidrug-resistant organisms. We used random-effect models to obtain pooled risk ratio estimates. Heterogeneity was evaluated with I2 estimation and the Cochran Q statistic. Pooled risk ratios for MRSA and VRE were assessed separately.
RESULTS: Fourteen studies met inclusion criteria and were included in the final review. Six studies discontinued CPs for both MRSA and VRE, 3 for MRSA only, 2 for VRE only, 2 for extended-spectrum β-lactamase-producing Escherichia coli, and 1 for Clostridium difficile infection. When study results were pooled, there was a trend toward reduction of MRSA infection after discontinuing CPs (pooled risk ratio, 0.84; 95% confidence interval, 0.70-1.02; P = .07) and a statistically significant reduction in VRE infection (pooled risk ratio, 0.82; 95% confidence interval, 0.72-0.94; P = .005).
CONCLUSIONS: Discontinuation of CPs for MRSA and VRE has not been associated with increased infection rates.

Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
PMID 29031432  Am J Infect Control. 2017 Oct 11;. doi: 10.1016/j.ajic.・・・
著者: Daniel J Morgan, Richard P Wenzel, Gonzalo Bearman
雑誌名: JAMA. 2017 Jul 25;318(4):329-330. doi: 10.1001/jama.2017.7419.
Abstract/Text
PMID 28654976  JAMA. 2017 Jul 25;318(4):329-330. doi: 10.1001/jama.201・・・
著者: Daniel J Morgan, Daniel J Diekema, Kent Sepkowitz, Eli N Perencevich
雑誌名: Am J Infect Control. 2009 Mar;37(2):85-93. doi: 10.1016/j.ajic.2008.04.257.
Abstract/Text BACKGROUND: Contact Precautions (CP) are a standard method for preventing patient-to-patient transmission of multiple drug-resistant organisms (MDROs) in hospital settings. With the ongoing worldwide concern for MDROs including methicillin-resistant Staphylococcus aureus (MRSA) and broadened use of active surveillance programs, an increasing number of patients are being placed on CP. Whereas few would argue that CP are an important tool in infection control, many reports and small studies have observed worse noninfectious outcomes in patients on CP. However, no review of this literature exists.
METHODS: We systematically reviewed the literature describing adverse outcomes associated with CP. We identified 15 studies published between 1989 and 2008 relating to adverse outcomes from CP. Nine were higher quality based on standardized collection of data and/or inclusion of control groups.
RESULTS: Four main adverse outcomes related to CP were identified in this review. These included less patient-health care worker contact, changes in systems of care that produce delays and more noninfectious adverse events, increased symptoms of depression and anxiety, and decreased patient satisfaction with care.
CONCLUSION: Although CP are recommended by the Centers for Disease Control and Prevention as an intervention to control spread of MDROs, our review of the literature demonstrates that this approach has unintended consequences that are potentially deleterious to the patient. Measures to ameliorate these deleterious consequences of CP are urgently needed.

PMID 19249637  Am J Infect Control. 2009 Mar;37(2):85-93. doi: 10.1016・・・
著者: Daniel J Morgan, Lisa Pineles, Michelle Shardell, Margaret M Graham, Shahrzad Mohammadi, Graeme N Forrest, Heather S Reisinger, Marin L Schweizer, Eli N Perencevich
雑誌名: Infect Control Hosp Epidemiol. 2013 Jan;34(1):69-73. doi: 10.1086/668775. Epub 2012 Nov 20.
Abstract/Text BACKGROUND AND OBJECTIVE: Contact precautions are a cornerstone of infection prevention but have also been associated with less healthcare worker (HCW) contact and adverse events. We studied how contact precautions modified HCW behavior in 4 acute care facilities.
DESIGN: Prospective cohort study.
PARTICIPANTS AND SETTING: Four acute care facilities in the United States performing active surveillance for methicillin-resistant Staphylococcus aureus.
METHODS: Trained observers performed "secret shopper" monitoring of HCW activities during routine care, using a standardized collection tool and fixed 1-hour observation periods.
RESULTS: A total of 7,743 HCW visits were observed over 1,989 hours. Patients on contact precautions had 36.4% fewer hourly HCW visits than patients not on contact precautions (2.78 vs 4.37 visits per hour; [Formula: see text]) as well as 17.7% less direct patient contact time with HCWs (13.98 vs 16.98 minutes per hour; [Formula: see text]). Patients on contact precautions tended to have fewer visitors (23.6% fewer; [Formula: see text]). HCWs were more likely to perform hand hygiene on exiting the room of a patient on contact precautions (63.2% vs 47.4% in rooms of patients not on contact precautions; [Formula: see text]).
CONCLUSION: Contact precautions were found to be associated with activities likely to reduce transmission of resistant pathogens, such as fewer visits and better hand hygiene at exit, while exposing patients on contact precautions to less HCW contact, less visitor contact, and potentially other unintended outcomes.

PMID 23221195  Infect Control Hosp Epidemiol. 2013 Jan;34(1):69-73. do・・・
著者: J F Gehanno, A Louvel, M Nouvellon, J-F Caillard, M Pestel-Caron
雑誌名: J Hosp Infect. 2009 Mar;71(3):256-62. doi: 10.1016/j.jhin.2008.11.015. Epub 2009 Jan 21.
Abstract/Text The aim of this study was to assess to what extent patients with meticillin-resistant Staphylococcus aureus (MRSA) at respiratory sites shed viable MRSA into the air of hospital rooms. We also evaluated whether the distance from the patient could influence the level of contamination. Air sampling was performed directly onto MRSA-selective agar in 24 hospital rooms containing patients with MRSA colonization or infection of the respiratory tract. Samplings were performed in duplicate at 0.5, 1 and 2-3 m from the patients' heads. Clinical and environmental isolates were compared using antimicrobial resistance patterns and pulsed-field gel electrophoresis. MRSA strains were isolated from 21 out of 24 rooms, in quantities varying from between 1 and 78 cfu/m3. In each of the 21 rooms, at least one of the environmental isolates was identical to a clinical isolate from the patient in that room. There was no significant difference in MRSA counts between the distance from the patient's head and the sampler. This study demonstrates that most patients with MRSA infection or colonisation of the respiratory tract shed viable MRSA into the air of their room. The results emphasise the need to study MRSA in air in more detail in order to improve infection control recommendations.

PMID 19162372  J Hosp Infect. 2009 Mar;71(3):256-62. doi: 10.1016/j.jh・・・
著者: Stefano Bassetti, Werner E Bischoff, Mark Walter, Barbara A Bassetti-Wyss, Lori Mason, Beth A Reboussin, Ralph B D'Agostino, Jack M Gwaltney, Michael A Pfaller, Robert J Sherertz
雑誌名: Infect Control Hosp Epidemiol. 2005 Feb;26(2):196-203. doi: 10.1086/502526.
Abstract/Text OBJECTIVE: To determine whether healthy adult nasal carriers of Staphylococcus aureus can disperse S. aureus into the air after rhinovirus infection.
DESIGN: We investigated the "cloud" phenomenon among adult nasal carriers of S. aureus experimentally infected with a rhinovirus. Eleven volunteers were studied for 16 days in an airtight chamber wearing street clothes, sterile garb, or sterile garb plus surgical mask; rhinovirus inoculation occurred on day 2. Daily quantitative air, nasal, and skin cultures for S. aureus; cold symptom assessment; and nasal rhinovirus cultures were performed.
SETTING: Wake Forest University School of Medicine, Winston-Salem, North Carolina.
PARTICIPANTS: Wake Forest University undergraduate or graduate students who had persistent nasal carriage of S. aureus for 4 or 8 weeks.
RESULTS: After rhinovirus inoculation, dispersal of S. aureus into the air increased 2-fold with peak increases up to 34-fold. Independent predictors of S. aureus dispersal included the time period after rhinovirus infection and wearing street clothes (P < .05). Wearing barrier garb but not a mask decreased dispersal of S. aureus into the air (P < .05).
CONCLUSION: Virus-induced dispersal of S. aureus into the air may have an important role in the transmission of S. aureus and other bacteria.

PMID 15756892  Infect Control Hosp Epidemiol. 2005 Feb;26(2):196-203. ・・・
著者: Ed Mangini, Sorana Segal-Maurer, Janice Burns, Annette Avicolli, Carl Urban, Noriel Mariano, Louise Grenner, Carl Rosenberg, James J Rahal
雑誌名: Infect Control Hosp Epidemiol. 2007 Nov;28(11):1261-6. doi: 10.1086/521658. Epub 2007 Sep 18.
Abstract/Text OBJECTIVE: To evaluate the efficacy of contact and droplet precautions in reducing the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections.
DESIGN: Before-after study.Setting. A 439-bed, university-affiliated community hospital.
METHODS: To identify inpatients infected or colonized with MRSA, we conducted surveillance of S. aureus isolates recovered from clinical culture and processed by the hospital's clinical microbiology laboratory. We then reviewed patient records for all individuals from whom MRSA was recovered. The rates of hospital-acquired MRSA infection were tabulated for each area where patients received nursing care. After a baseline period, contact and droplet precautions were implemented in all intensive care units (ICUs). Reductions in the incidence of hospital-acquired MRSA infection in ICUs led to the implementation of contact precautions in non-ICU patient care areas (hereafter, "non-ICU areas"), as well. Droplet precautions were discontinued. An analysis comparing the rates of hospital-acquired MRSA infection during different intervention periods was performed.
RESULTS: The combined baseline rate of hospital-acquired MRSA infection was 10.0 infections per 1,000 patient-days in the medical ICU (MICU) and surgical ICU (SICU) and 0.7 infections per 1,000 patient-days in other ICUs. Following the implementation of contact and droplet precautions, combined rates of hospital-acquired MRSA infection in the MICU and SICU decreased to 4.3 infections per 1,000 patient-days (95% confidence interval [CI], 0.17-0.97; P=.03). There was no significant change in hospital-acquired MRSA infection rates in other ICUs. After the discontinuation of droplet precautions, the combined rate in the MICU and SICU decreased further to 2.5 infections per 1,000 patient-days. This finding was not significant (P=.43). In the non-ICU areas that had a high incidence of hospital-acquired MRSA infection, the rate prior to implementation of contact precautions was 1.3 infections per 1,000 patient-days. After the implementation of contact precautions, the rate in these areas decreased to 0.9 infections per 1,000 patient-days (95% CI, 0.47-0.94; P=.02).
CONCLUSION: The implementation of contact precautions significantly decreased the rate of hospital-acquired MRSA infection, and discontinuation of droplet precautions in the ICUs led to a further reduction. Additional studies evaluating specific infection control strategies are needed.

PMID 17926277  Infect Control Hosp Epidemiol. 2007 Nov;28(11):1261-6. ・・・
著者: D Pittet, S Hugonnet, S Harbarth, P Mourouga, V Sauvan, S Touveneau, T V Perneger
雑誌名: Lancet. 2000 Oct 14;356(9238):1307-12.
Abstract/Text BACKGROUND: Hand hygiene prevents cross infection in hospitals, but compliance with recommended instructions is commonly poor. We attempted to promote hand hygiene by implementing a hospital-wide programme, with special emphasis on bedside, alcohol-based hand disinfection. We measured nosocomial infections in parallel.
METHODS: We monitored the overall compliance with hand hygiene during routine patient care in a teaching hospital in Geneva, Switzerland, before and during implementation of a hand-hygiene campaign. Seven hospital-wide observational surveys were done twice yearly from December, 1994, to December, 1997. Secondary outcome measures were nosocomial infection rates, attack rates of methicillin-resistant Staphylococcus aureus (MRSA), and consumption of handrub disinfectant.
FINDINGS: We observed more than 20,000 opportunities for hand hygiene. Compliance improved progressively from 48% in 1994, to 66% in 1997 (p<0.001). Although recourse to handwashing with soap and water remained stable, frequency of hand disinfection substantially increased during the study period (p<0.001). This result was unchanged after adjustment for known risk factors of poor adherence. Hand hygiene improved significantly among nurses and nursing assistants, but remained poor among doctors. During the same period, overall nosocomial infection decreased (prevalence of 16.9% in 1994 to 9.9% in 1998; p=0.04), MRSA transmission rates decreased (2.16 to 0.93 episodes per 10,000 patient-days; p<0.001), and the consumption of alcohol-based handrub solution increased from 3.5 to 15.4 L per 1000 patient-days between 1993 and 1998 (p<0.001).
INTERPRETATION: The campaign produced a sustained improvement in compliance with hand hygiene, coinciding with a reduction of nosocomial infections and MRSA transmission. The promotion of bedside, antiseptic handrubs largely contributed to the increase in compliance.

PMID 11073019  Lancet. 2000 Oct 14;356(9238):1307-12.
著者: Michael A Smit, Ann-Christine Nyquist, James K Todd
雑誌名: Emerg Infect Dis. 2013 Nov;19(11):1855-8. doi: 10.3201/eid1011.121547.
Abstract/Text In Colorado, USA, diagnoses coded as toxic shock syndrome (TSS) constituted 27.3% of infectious shock cases during 1993-2006. The incidence of staphylococcal TSS did not change significantly overall or in female patients 10-49 years of age but increased for streptococcal TSS. TSS may be underrecognized among all ages and both sexes.

PMID 24188357  Emerg Infect Dis. 2013 Nov;19(11):1855-8. doi: 10.3201/・・・
著者: J P Davis, M T Osterholm, C M Helms, J M Vergeront, L A Wintermeyer, J C Forfang, L A Judy, J Rondeau, W L Schell
雑誌名: J Infect Dis. 1982 Apr;145(4):441-8.
Abstract/Text Clinical and laboratory findings were examined in 80 nonfatal cases of toxic-shock syndrome (TSS) which occurred in women from Minnesota, Wisconsin, and Iowa between October 1, 1979, and September 19, 1980. Among the clinical and laboratory factors reviewed, the presence of physician-diagnosed shock was the factor that most significantly correlated with other organ involvement. Vomiting, mucous membrane hyperemia, myalgias, and abnormal urinalysis were the factors noted to be manifest as frequently in the absence as in the presence of shock. Twenty-seven patients had recurrent episodes of TSS. The use of antistaphylococcal antibiotics during the initial TSS episode and the subsequent discontinuation of tampon use were independently statistically significantly associated with a decreased risk of recurrent illness. Only 44 of 54 patients had cervical/vaginal cultures positive for Staphylococcus aureus, a result indicating that a negative cervical/vaginal culture does not preclude the diagnosis of TSS.

PMID 7069224  J Infect Dis. 1982 Apr;145(4):441-8.
著者: Donald E Low
雑誌名: Crit Care Clin. 2013 Jul;29(3):651-75. doi: 10.1016/j.ccc.2013.03.012.
Abstract/Text Toxic shock syndrome (TSS) is primarily the result of a superantigen-mediated cytokine storm and M protein-mediated neutrophil activation, resulting in the release of mediators leading to respiratory failure, vascular leakage, and shock. Mortality for streptococcal TSS still hovers at 50%. There is evidence to support a role for intravenous immunoglobulin (IVIG) in the treatment of streptococcal TSS. An observational study suggests that an initial conservative surgical approach combined with the use of immune modulators, such as IVIG, may reduce the morbidity associated with extensive surgical exploration in hemodynamically unstable patients without increasing mortality.

Copyright © 2013 Elsevier Inc. All rights reserved.
PMID 23830657  Crit Care Clin. 2013 Jul;29(3):651-75. doi: 10.1016/j.c・・・
著者:
雑誌名: MMWR Recomm Rep. 1997 May 2;46(RR-10):1-55.
Abstract/Text State and local public health officials rely on health-care providers, laboratories, and other public health personnel to report the occurrence of notifiable diseases to state and local health departments. Without such data, trends cannot be accurately monitored, unusual occurrences of diseases might not be detected, and the effectiveness of intervention activities cannot be easily evaluated. In the United States, requirements for reporting diseases are mandated by state laws or regulations, and the list of reportable diseases in each state differs. In October 1990, in collaboration with the Council of State and Territorial Epidemiologists, CDC published Case Definitions for Public Health Surveillance (MMWR 1990;39[No. RR-13]), which, for the first time, provided uniform criteria for reporting cases. This report provides updated uniform criteria for state health department personnel to use when reporting the nationally notifiable infectious diseases listed in Part 1 of this report. A revision date is listed for each case definition that has been revised. Newly generated case definitions that have not been published previously are designated as "adopted" on the specified date. Case definitions for some infectious conditions not designated as nationally notifiable are included in Part 2 of this report. Some of these conditions may have been nationally notifiable or may become so; definitions are included here to facilitate interpretation of data for these diseases. These conditions may be reportable in some states.

PMID 9148133  MMWR Recomm Rep. 1997 May 2;46(RR-10):1-55.
著者: R A Hajjeh, A Reingold, A Weil, K Shutt, A Schuchat, B A Perkins
雑誌名: Emerg Infect Dis. 1999 Nov-Dec;5(6):807-10. doi: 10.3201/eid0506.990611.
Abstract/Text Menstrual toxic shock syndrome (TSS) emerged as a public health threat to women of reproductive age in 1979 80. We reviewed surveillance data for the period 1979 to 1996, when 5,296 cases were reported, and discuss changes in the epidemiologic features of TSS.

PMID 10603216  Emerg Infect Dis. 1999 Nov-Dec;5(6):807-10. doi: 10.320・・・
著者: Jessica Darenberg, Bo Söderquist, Birgitta Henriques Normark, Anna Norrby-Teglund
雑誌名: Clin Infect Dis. 2004 Mar 15;38(6):836-42. doi: 10.1086/381979. Epub 2004 Mar 1.
Abstract/Text Administration of intravenous polyspecific immunoglobulin G (IVIG) has been proposed as adjunctive therapy for toxic shock syndrome caused by Streptococcus pyogenes or Staphylococcus aureus. We investigated whether superantigen-containing culture supernatants prepared from streptococcal isolates (n=21) and staphylococcal isolates (n=20) from cases of severe sepsis were inhibited to an equal extent by IVIG in proliferation experiments that used human peripheral blood mononuclear cells. All 3 IVIG preparations tested were highly efficient in neutralizing the superantigens, and most supernatants were completely inhibited at concentrations ranging from 0.05 to 2.5 mg IVIG/mL. An important finding was that culture supernatants from S. pyogenes isolates were consistently inhibited to a greater extent than those of S. aureus isolates (P<.01). The findings demonstrate that staphylococcal superantigens are not inhibited as efficiently as streptococcal superantigens by IVIG, and, hence, a higher dose of IVIG may be required for therapy of staphylococcal toxic shock syndrome in order to achieve protective titers and clinical efficacy.

PMID 14999628  Clin Infect Dis. 2004 Mar 15;38(6):836-42. doi: 10.1086・・・
著者: Elaine Scallan, Robert M Hoekstra, Frederick J Angulo, Robert V Tauxe, Marc-Alain Widdowson, Sharon L Roy, Jeffery L Jones, Patricia M Griffin
雑誌名: Emerg Infect Dis. 2011 Jan;17(1):7-15. doi: 10.3201/eid1701.091101p1.
Abstract/Text Estimates of foodborne illness can be used to direct food safety policy and interventions. We used data from active and passive surveillance and other sources to estimate that each year 31 major pathogens acquired in the United States caused 9.4 million episodes of foodborne illness (90% credible interval [CrI] 6.6-12.7 million), 55,961 hospitalizations (90% CrI 39,534-75,741), and 1,351 deaths (90% CrI 712-2,268). Most (58%) illnesses were caused by norovirus, followed by nontyphoidal Salmonella spp. (11%), Clostridium perfringens (10%), and Campylobacter spp. (9%). Leading causes of hospitalization were nontyphoidal Salmonella spp. (35%), norovirus (26%), Campylobacter spp. (15%), and Toxoplasma gondii (8%). Leading causes of death were nontyphoidal Salmonella spp. (28%), T. gondii (24%), Listeria monocytogenes (19%), and norovirus (11%). These estimates cannot be compared with prior (1999) estimates to assess trends because different methods were used. Additional data and more refined methods can improve future estimates.

PMID 21192848  Emerg Infect Dis. 2011 Jan;17(1):7-15. doi: 10.3201/eid・・・
著者: Jacques-Antoine Hennekinne, Marie-Laure De Buyser, Sylviane Dragacci
雑誌名: FEMS Microbiol Rev. 2012 Jul;36(4):815-36. doi: 10.1111/j.1574-6976.2011.00311.x. Epub 2011 Nov 8.
Abstract/Text Staphylococcal food poisoning (SFP) is one of the most common food-borne diseases and results from the ingestion of staphylococcal enterotoxins (SEs) preformed in food by enterotoxigenic strains of Staphylococcus aureus. To date, more than 20 SEs have been described: SEA to SElV. All of them have superantigenic activity whereas half of them have been proved to be emetic, representing a potential hazard for consumers. This review, divided into four parts, will focus on the following: (1) the worldwide story of SFP outbreaks, (2) the characteristics and behaviour of S. aureus in food environment, (3) the toxinogenic conditions and characteristics of SEs, and (4) SFP outbreaks including symptomatology, occurrence in the European Union and currently available methods used to characterize staphylococcal outbreaks.

© European Union 2011 Published by Blackwell Publishing Ltd.
PMID 22091892  FEMS Microbiol Rev. 2012 Jul;36(4):815-36. doi: 10.1111・・・
著者: T Steinmetz, N Eliakim-Raz, E Goldberg, L Leibovici, D Yahav
雑誌名: Clin Microbiol Infect. 2015 Jul;21(7):665-73. doi: 10.1016/j.cmi.2015.04.003. Epub 2015 Apr 14.
Abstract/Text Recent Infectious Diseases Society of America guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend maintaining vancomycin trough concentrations of 15-20 mg/L for serious infections. We conducted a systematic review and meta-analysis of all studies assessing the impact of low (<15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough level on the efficacy of MRSA infections treatment. Four prospective and 12 retrospective studies were included (2003 participants). No significant difference was demonstrated between low and high vancomycin trough level for the outcome of all-cause mortality (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.78-1.46, I(2) = 28%). In studies evaluating mainly MRSA pneumonia, there was significantly higher mortality with low vancomycin level (OR 1.78, 95% CI 1.11-2.84). No significant difference was demonstrated in treatment failure rates (OR 1.25, 95% CI 0.88-1.78, I(2) = 51%). However, excluding one outlier study from the analysis, treatment failure became significantly higher in patients with low vancomycin trough level (OR 1.46, 95% CI 1.12-1.91, I(2) = 16%). Microbiologic failure rates were significantly higher in patients with low vancomycin levels (OR 1.56, 95% CI 1.08-2.26, I(2) = 0%). Nephrotoxicity was significantly higher with vancomycin levels of ≥ 15 mg/L. However, no cases of irreversible renal damage were reported. Current data on the effectiveness of higher vancomycin trough levels in the treatment of MRSA infections are limited to few prospective and mainly retrospective studies. Our findings support the current recommendations for maintaining vancomycin trough levels of ≥ 15 mg/L in the treatment of severe MRSA infections, although no difference in all-cause mortality was observed.

Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 25887712  Clin Microbiol Infect. 2015 Jul;21(7):665-73. doi: 10.1・・・
著者: Akira Watanabe, Katsunori Yanagihara, Shigeru Kohno, Toshiharu Matsushima, HAP study group
雑誌名: Intern Med. 2008;47(4):245-54. Epub 2008 Feb 15.
Abstract/Text OBJECTIVE: The aim of this study was to investigate the pathophysiology of hospital-acquired pneumonia (HAP) and the clinical efficacy of its first-line treatment and to examine the validity of "the Japanese Respiratory Society (JRS) Guidelines for management of HAP".
METHODOLOGY: The observational survey was conducted during the period of June 2002-May 2004 and patients with HAP were prospectively surveyed using the consecutive enrollment method. A total of 1,356 patients from 254 hospitals nationwide were analyzed. Clinical response to first-line antibiotics was evaluated at the end of the medication.
RESULTS: The 30-day mortality rate was 19.8%. Patients were classified into four groups according to the JRS guideline criteria. There were remarkable variances in the number of cases of each group. Mild/moderate pneumonia with no risk factors (group I) accounted for 0.3% of all cases. The mortality rate tended to be higher, as clinical conditions became more serious (group II < III < IV). Alternatively, though categorized in the same group (group III), there was a difference in the mortality rate by the severity of pneumonia (severe cases 32.2% vs. moderate cases 11.0%). First-line medication using carbapenems accounted for 61.7% of total cases. The efficacy rate of guideline-concordant therapy was significantly higher than that of guideline-discordant therapy (54.2% vs. 41.7%).
CONCLUSIONS: This is the first nationwide study on HAP in Japan. The clinical characteristics and prognosis of HAP were elucidated. Review of the current classification of the disease is required and these results provide valuable information for the next revision of the guidelines.

PMID 18277024  Intern Med. 2008;47(4):245-54. Epub 2008 Feb 15.
著者: Shelley S Magill, Jonathan R Edwards, Wendy Bamberg, Zintars G Beldavs, Ghinwa Dumyati, Marion A Kainer, Ruth Lynfield, Meghan Maloney, Laura McAllister-Hollod, Joelle Nadle, Susan M Ray, Deborah L Thompson, Lucy E Wilson, Scott K Fridkin, Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team
雑誌名: N Engl J Med. 2014 Mar 27;370(13):1198-208. doi: 10.1056/NEJMoa1306801.
Abstract/Text BACKGROUND: Currently, no single U.S. surveillance system can provide estimates of the burden of all types of health care-associated infections across acute care patient populations. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care-associated infections in acute care hospitals and generate updated estimates of the national burden of such infections.
METHODS: We defined health care-associated infections with the use of National Healthcare Safety Network criteria. One-day surveys of randomly selected inpatients were performed in participating hospitals. Hospital personnel collected demographic and limited clinical data. Trained data collectors reviewed medical records retrospectively to identify health care-associated infections active at the time of the survey. Survey data and 2010 Nationwide Inpatient Sample data, stratified according to patient age and length of hospital stay, were used to estimate the total numbers of health care-associated infections and of inpatients with such infections in U.S. acute care hospitals in 2011.
RESULTS: Surveys were conducted in 183 hospitals. Of 11,282 patients, 452 had 1 or more health care-associated infections (4.0%; 95% confidence interval, 3.7 to 4.4). Of 504 such infections, the most common types were pneumonia (21.8%), surgical-site infections (21.8%), and gastrointestinal infections (17.1%). Clostridium difficile was the most commonly reported pathogen (causing 12.1% of health care-associated infections). Device-associated infections (i.e., central-catheter-associated bloodstream infection, catheter-associated urinary tract infection, and ventilator-associated pneumonia), which have traditionally been the focus of programs to prevent health care-associated infections, accounted for 25.6% of such infections. We estimated that there were 648,000 patients with 721,800 health care-associated infections in U.S. acute care hospitals in 2011.
CONCLUSIONS: Results of this multistate prevalence survey of health care-associated infections indicate that public health surveillance and prevention activities should continue to address C. difficile infections. As device- and procedure-associated infections decrease, consideration should be given to expanding surveillance and prevention activities to include other health care-associated infections.

PMID 24670166  N Engl J Med. 2014 Mar 27;370(13):1198-208. doi: 10.105・・・
著者: Marta Francesca Di Pasquale, Giovanni Sotgiu, Andrea Gramegna, Dejan Radovanovic, Silvia Terraneo, Luis F Reyes, Jan Rupp, Juan González Del Castillo, Francesco Blasi, Stefano Aliberti, Marcos I Restrepo, GLIMP Investigators
雑誌名: Clin Infect Dis. 2019 Apr 24;68(9):1482-1493. doi: 10.1093/cid/ciy723.
Abstract/Text BACKGROUND: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia.
METHODS: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor.
RESULTS: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non-community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001).
CONCLUSIONS: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PMID 31222287  Clin Infect Dis. 2019 Apr 24;68(9):1482-1493. doi: 10.1・・・
著者: Krishnan Raghavendran, Jiping Wang, Christopher Belber, Sarojini R Misra, Kimberly Brunton, Eileen Berbary, Mark S Burke, Curtis E Haas
雑誌名: J Trauma. 2007 Jun;62(6):1377-82; discussion 1382-3. doi: 10.1097/TA.0b013e3180479889.
Abstract/Text BACKGROUND: Ventilator-associated pneumonia (VAP) is diagnosed in about 30% to 50% of critically ill postsurgical and trauma patients. Early appropriate antibiotic therapy has been associated with improved survival rates. The diagnosis, however, continues to be a challenge. We routinely employ clinical pulmonary infection scores to warrant a bronchoalveolar lavage (BAL) quantitative culture to subsequently diagnose VAP. Presumptive antibiotic therapy for the first 48 to 72 hours is based on the sputum Gram stain, obtained at the time of BAL. This study was conducted to analyze the predictive value of sputum Gram stain for selecting appropriate early antibiotic therapy for VAP as confirmed by a BAL quantitative culture (>10 CFU/mL considered diagnostic).
METHODS: The retrospective analysis included 124 consecutive intensive care unit patients with 186 identified episodes of presumed VAP from December 2002 to June 2006. VAP episodes were identified by a clinical pulmonary infection score > or =6, availability of a sputum Gram stain, and a corresponding quantitative culture result from a BAL sample.
RESULTS: The overall correlation between Gram stain and subsequent organism identified on the BAL quantitative culture was only fair with a kappa score of 0.314. The best predictive value calculated was for the category of negative Gram stain. However, in 10 of 45 episodes where the sputum Gram stain did not identify a predominant organism, the BAL culture isolated pathogenic strains. Pseudomonas sp. was the most common bacteria isolated from the BAL samples.
CONCLUSIONS: Irrespective of sputum Gram stain, presumptive triple antibiotic coverage should be instituted to provide dual antibiotic coverage for gram-negative bacilli, and vancomycin for gram-positive cocci. Additionally, identification of no organisms in the sputum Gram stain should still prompt broad-spectrum antibiotic coverage until the final results of the BAL quantitative culture are available.

PMID 17563652  J Trauma. 2007 Jun;62(6):1377-82; discussion 1382-3. do・・・
著者: M Albert, J O Friedrich, N K J Adhikari, A G Day, C Verdant, Daren K Heyland, Canadian Critical Care Trials Group
雑誌名: J Crit Care. 2008 Mar;23(1):74-81. doi: 10.1016/j.jcrc.2008.01.004.
Abstract/Text PURPOSE: Gram stains of endotracheal aspirates (EA) and bronchoalveolar lavages (BAL) may guide empiric antibiotic therapy in critically ill patients with suspected ventilator-associated pneumonia (VAP). Previous studies differ regarding the ability of the Gram stain to predict final culture results. The aim of the present study was to evaluate the relationship between EA or BAL Gram stains and final culture results in intensive care unit patients with a suspected VAP.
MATERIAL AND METHODS: We retrospectively analyzed data from the Canadian multicenter VAP study to correlate EA or BAL Gram stain and final culture results. We categorized Gram stains as Gram positive (GP) and Gram negative (GN) if any GP or GN organisms respectively were seen on staining. Cultures were considered "positive" if they yielded pathogenic organisms on final results.
RESULTS: Seven hundred forty patients were enrolled in the study; 35 did not have a Gram stain done leaving 350 BALs and 355 EAs from 705 patients. Pooling BAL and EA results, we found the overall agreement between Gram stain class and pathogenic bacteria culture results to be poor (kappa = 0.36; 95% CI, 0.31-0.40). Among specimens with Gram stains showing no organisms, 99 (30%) of 331 grew pathogenic organisms. Among specimens with Gram stains showing no GN organisms, 113 (25%) of 452 grew pathogenic GN organisms. Among specimens with Gram stains showing no GP organisms, 45 (11%) of 428 grew pathogenic GP organisms.
CONCLUSIONS: Gram stains performed for clinically suspected VAP poorly predict the final culture result and thus have a limited role in guiding initial empiric antibiotic therapy in such patients.

PMID 18359424  J Crit Care. 2008 Mar;23(1):74-81. doi: 10.1016/j.jcrc.・・・
著者: Maren C Cowley, David J Ritchie, Nicholas Hampton, Marin H Kollef, Scott T Micek
雑誌名: Chest. 2019 Jan;155(1):53-59. doi: 10.1016/j.chest.2018.10.014. Epub 2018 Oct 25.
Abstract/Text BACKGROUND: In culture-positive nosocomial pneumonia, de-escalation (DE) from broad-spectrum empirical antimicrobials to narrower-spectrum agents has shown to decrease broad-spectrum antibiotic use without compromising patient outcomes. However, uncertainty exists regarding the safety of anti-methicillin-resistant Staphylococcus aureus (MRSA) agent DE in culture-negative nosocomial pneumonia. This study aimed to determine if anti-MRSA agent DE in culture-negative nosocomial pneumonia affects 28-day and hospital mortality, ICU and hospital length of stay (LOS), treatment failure, and safety.
METHODS: This single-center retrospective cohort study included adult patients admitted from 2012 to 2017 with nosocomial pneumonia and a negative respiratory culture. DE was defined as anti-MRSA agent discontinuation within 4 days of initiation. Secondary outcomes included hospital mortality, hospital and ICU LOS, treatment failure, and occurrence of acute kidney injury (AKI).
RESULTS: Of 279 patients included, 92 were in the DE group and 187 were in the no DE (NDE) group. Patients who were not de-escalated received 5 more days of MRSA coverage than patients who were de-escalated; however, there was no difference in 28-day mortality (NDE group, 28% vs DE group, 23%; difference, -5.5%; 95% CI, -16.1 to 6.5). Patients who were de-escalated had shorter hospital (DE group, 15 days vs NDE group, 20 days; difference, 3.2 days; 95% CI, 0.1-6.4) and ICU (DE group, 10 days vs NDE group, 13 days; difference, 2.2 days; 95% CI, -0.3 to 4.9) LOSs after the index date. The incidence of AKI was significantly higher in patients who were not de-escalated (DE group, 36% vs NDE group, 50%; difference, -13.8%; 95% CI, -26.9 to -0.4).
CONCLUSIONS: Although anti-MRSA agent DE in culture-negative nosocomial pneumonia did not affect 28-day mortality, it was associated with a shorter hospital LOS and lower incidence of AKI.

Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
PMID 30621854  Chest. 2019 Jan;155(1):53-59. doi: 10.1016/j.chest.2018・・・
著者: Anna M Ferrara
雑誌名: Int J Antimicrob Agents. 2007 Jul;30(1):19-24. doi: 10.1016/j.ijantimicag.2007.02.011. Epub 2007 May 1.
Abstract/Text Nosocomial pneumonia and ventilator-assisted pneumonia may be polymicrobial and can be caused by a wide spectrum of pathogens. Potentially multidrug-resistant microorganisms often represent the 'core' pathogens of the most severe infections. Among Gram-positive pathogens, methicillin-resistant Staphylococcus aureus (MRSA) plays a key role, mainly in mechanically ventilated patients or in patients with specific risk factors. The mainstay of treatment for MRSA pneumonia has been glycopeptide antibiotics, i.e. vancomycin and, to a lesser extent, teicoplanin. However, owing to its insufficient penetration into lung compartments, vancomycin may result in therapeutic failure or slow clinical responses. Moreover, vancomycin serum levels must be monitored in order to minimise nephrotoxicity and to maximise the concentration in the lung. Finally, the emergence of staphylococci isolates with reduced susceptibility to vancomycin suggests that glycopeptides should no longer be considered as first-line antibacterial agents for Gram-positive lung infections. Among new therapeutic options, linezolid may be an appropriate choice for MRSA pulmonary infections owing to its good pharmacokinetic profile in the lung and its acceptable tolerability, especially in patients with renal insufficiency or in those receiving other nephrotoxic agents. However, to contain the increasing emergence of drug resistance among hospitalised patients, these novel antimicrobial agents should be used judiciously, restricting their use to patients not responsive to, or intolerant of, glycopeptides. Other new drugs under development appear to be promising and deserve further evaluation.

PMID 17475449  Int J Antimicrob Agents. 2007 Jul;30(1):19-24. doi: 10.・・・
著者: Marc H Scheetz, Richard G Wunderink, Michael J Postelnick, Gary A Noskin
雑誌名: Pharmacotherapy. 2006 Apr;26(4):539-50. doi: 10.1592/phco.26.4.539.
Abstract/Text Vancomycin as the drug of choice for treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia has been called into question on the basis of therapeutic failures. In patients with MRSA pneumonia, treatment failures are probably due to the complex interplay of variables affecting the host-antimicrobial-pathogen interrelationship. However, it has been suggested that decreased penetration of vancomycin into the lungs may contribute. This review explores physiochemical and physiologic variables that affect pulmonary penetration and describes methods used in quantifying pulmonary vancomycin concentrations. Most important, findings are evaluated in the clinical context of the chemotherapeutic options available for treatment of MRSA pneumonia. The possibility of increased serum vancomycin concentrations as a method to optimize current treatment outcomes is also explored.

PMID 16553514  Pharmacotherapy. 2006 Apr;26(4):539-50. doi: 10.1592/ph・・・
著者: Michael Rybak, Ben Lomaestro, John C Rotschafer, Robert Moellering, William Craig, Marianne Billeter, Joseph R Dalovisio, Donald P Levine
雑誌名: Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98. doi: 10.2146/ajhp080434.
Abstract/Text
PMID 19106348  Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98. doi: 10・・・
著者: Levita K Hidayat, Donald I Hsu, Ryan Quist, Kimberly A Shriner, Annie Wong-Beringer
雑誌名: Arch Intern Med. 2006 Oct 23;166(19):2138-44. doi: 10.1001/archinte.166.19.2138.
Abstract/Text BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL.
METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses.
RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents.
CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.

PMID 17060545  Arch Intern Med. 2006 Oct 23;166(19):2138-44. doi: 10.1・・・
著者: Thomas P Lodise, Nimish Patel, Ben M Lomaestro, Keith A Rodvold, George L Drusano
雑誌名: Clin Infect Dis. 2009 Aug 15;49(4):507-14. doi: 10.1086/600884.
Abstract/Text BACKGROUND: Data suggest that higher doses of vancomycin can increase the risk of nephrotoxicity. No study has been undertaken to determine the pharmacodynamic index (ie, the area under the curve [AUC] or the trough value) that best describes the relationship between vancomycin exposure and onset of nephrotoxicity.
METHODS: A retrospective study was conducted among patients who received vancomycin for a suspected or proven gram-positive infection during the period from 1 January 2005 through 31 December 2006 at Albany Medical Center Hospital. Patients were included in our study if they (1) were > or =18 years old, (2) had an absolute neutrophil count of > or =1000 cells/mm(3), (3) received vancomycin for >48 h, (4) had 1 vancomycin trough level collected within 96 h of vancomycin therapy, and (5) had a baseline serum creatinine level of <2.0 mg/dL. Patients were excluded if they (1) had a diagnosis of cystic fibrosis, (2) received intravenous contrast dye within 7 days of starting vancomycin or during therapy, or (3) required vasopressor support during therapy. Demographics, comorbid conditions, and treatment data were collected. The highest observed vancomycin trough value within 96 h of initiation of vancomycin therapy and the estimated vancomycin AUC were analyzed as measures of vancomycin exposure. The vancomycin AUC value from 0 to 24 h at steady state (in units of mg x h/L) for each patient was estimated by use of the maximum a posteriori probability Bayesian procedure in ADAPT II. Nephrotoxicity was defined as an increase in serum creatinine level of 0.5 mg/dL or 50%, whichever was greater, following initiation of vancomycin therapy. Logistic and Cox proportional hazards regression models identified the vancomycin pharmacodynamic index that best describes the relationship between vancomycin exposure and toxicity.
RESULTS: During the study period, 166 patients met the inclusion criteria. Both initial vancomycin trough values and 0-24-h at steady state AUC values were associated with nephrotoxicity in the bivariate analyses. However, the vancomycin trough value, modeled as a continuous variable, was the only vancomycin exposure variable associated with nephrotoxicity in the multivariate analyses.
CONCLUSIONS: The results indicate that a vancomycin exposure-toxicity response relationship exists. The vancomycin trough value is the pharmacodynamic index that best describes this association.

PMID 19586413  Clin Infect Dis. 2009 Aug 15;49(4):507-14. doi: 10.1086・・・
著者: Thomas P Lodise, Ben Lomaestro, Jeffrey Graves, G L Drusano
雑誌名: Antimicrob Agents Chemother. 2008 Apr;52(4):1330-6. doi: 10.1128/AAC.01602-07. Epub 2008 Jan 28.
Abstract/Text Recent guidelines recommend vancomycin trough concentrations between 15 and 20 mg/liter. In response, some clinicians increased vancomycin dosing to >or=4 g/day. Scant data are available regarding toxicities associated with higher vancomycin doses. The purpose of this study was to examine vancomycin-associated nephrotoxicity at >or=4 g/day. To accomplish the study objective, a cohort study among a random selection of patients receiving vancomycin or linezolid between 2005 and 2006 was performed. Patients were included if they (i) were >or=18 years of age, (ii) were nonneutropenic, (iii) were on therapy for >48 h, (iv) had baseline serum creatinine levels of <2.0 mg/dl, (v) did not suffer from cystic fibrosis, and (vi) had no intravenous contrast dye within the previous 7 days. For drug exposure, three treatment strata were created: standard vancomycin dose (<4 g/day), high vancomycin dose (>or=4 g/day), and linezolid. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/dl or 50%, whichever was greater, after therapy initiation. Stratified Kaplan-Meier analysis and Cox modeling were used to compare times to nephrotoxicity across groups. During the study, 246 patients on vancomycin (26 patients taking >or=4 g/day and 220 patients taking <4 g/day) and 45 patients on linezolid met the criteria. A significant difference in nephrotoxicity between patients receiving >or=4 g vancomycin/day, those receiving <4 g vancomycin/day, and those receiving linezolid was noted (34.6%, 10.9%, and 6.7%, respectively; P = 0.001), and Kaplan-Meier analysis identified significant differences in time to nephrotoxicity for the high-vancomycin-dose cohort compared to those for groups taking the standard dose and linezolid. In the Cox model, patients taking >or=4 g vancomycin/day, a total body weight of >or=101.4 kg, estimated creatinine clearance of
PMID 18227177  Antimicrob Agents Chemother. 2008 Apr;52(4):1330-6. doi・・・
著者: Avisheh Forouzesh, Pamela A Moise, George Sakoulas
雑誌名: Antimicrob Agents Chemother. 2009 Feb;53(2):483-6. doi: 10.1128/AAC.01088-08. Epub 2008 Nov 10.
Abstract/Text Nephrotoxicity and ototoxicity have historically been documented as relatively rare complications of vancomycin monotherapy. Recent reports have linked aggressive vancomycin dosing strategies to significant risks of nephrotoxicity. We evaluated the rate of high-frequency hearing loss detected by audiometry for patients on vancomycin therapy. For this purpose, we used retrospective case-control analysis of audiometry results for patients on vancomycin therapy for whom baseline and follow-up exams were available. Analysis of 89 patients for whom audiograms were performed after an average of 27 days of vancomycin therapy showed a 12% rate of high-frequency hearing loss, with a trend in univariate analysis toward a higher rate with advanced age. The mean of the highest vancomycin trough levels for both patients with worsening audiograms and those without worsening audiograms was 19 mg/liter. Regression tree modeling demonstrated that for patients <53 years old, the rate of high-frequency hearing loss detected by audiogram was 0%, while for patients >53 years old, the incidence was 19% (P = 0.008). We conclude that a significant rate of high-frequency hearing loss in older patients receiving vancomycin monotherapy was detected by audiometry. While these data urge caution against continued indiscriminate vancomycin dose escalation to treat infections caused by Staphylococcus aureus strains for which vancomycin MICs are 2 mg/liter, further prospective studies are needed to determine the clinical significance and reversibility of these effects.

PMID 19001107  Antimicrob Agents Chemother. 2009 Feb;53(2):483-6. doi:・・・
著者: Gary E Stein, Elizabeth M Wells
雑誌名: Curr Med Res Opin. 2010 Mar;26(3):571-88. doi: 10.1185/03007990903512057.
Abstract/Text BACKGROUND: The rising prevalence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) and the recent emergence of community-associated MRSA are major clinical, public health, and economic challenges. MRSA is a leading cause of nosocomial pneumonia and complicated skin and soft-tissue infections (cSSTI). Vancomycin and linezolid are two commonly used antimicrobial agents with activity against Gram-positive pathogens, particularly MRSA, that are used to treat both nosocomial pneumonia and cSSTI. Recently, the therapeutic efficacy of vancomycin in the treatment of hospitalized patients with MRSA infections has been questioned due to the emergence of MRSA strains with reduced susceptibility to vancomycin together with concerns related to inadequate dosing and poor tissue penetration of the drug.
SCOPE: A literature review was conducted to investigate the pharmacokinetics and pulmonary and tissue penetration of vancomycin and linezolid. Using MEDLINE and EMBASE, the most relevant articles in English published over the past 25 years (up to October 2008) were identified and summarized. Studies in human volunteers and adult patients that measured concentrations of antibiotic in serum, epithelial lining fluid (ELF), and tissue were selected for further review.
FINDINGS: For both drugs, pharmacokinetic studies were conducted in diverse patient populations and employed varying techniques to measure tissue concentrations. Vancomycin concentrations in ELF ranged from 5 to 25% of simultaneous plasma levels, while concentrations in whole homogenized lung tissue were slightly higher (24-41%). Distribution of vancomycin into soft tissue was variable. For linezolid, overall mean concentrations in ELF and in soft tissue were generally similar or higher than simultaneous plasma levels, although variability in tissue penetration across studies in healthy volunteers and patients was seen.
LIMITATIONS: The studies included in this review vary greatly in their designs and patient populations; this, together with methodologic difficulties, limits the interpretation of the data.
CONCLUSIONS: In the absence of clinical data correlating ELF concentrations and clinical outcome, the clinical significance of differences in pulmonary penetration of vancomycin and linezolid is unknown. Higher vancomycin serum concentrations may be necessary to achieve appropriate lung concentrations to optimize treatment outcomes. Linezolid demonstrates adequate penetration into lung and other soft issues with sustained concentrations above the minimum inhibitory concentrations for susceptible pathogens, including MRSA, for the majority of the dosing interval. Examination of the pharmacokinetic data adds insights not provided by the clinical trial data and together provides clinicians with a more comprehensive basis for selecting appropriate antimicrobial therapy for the treatment of serious MRSA infections.

PMID 20055750  Curr Med Res Opin. 2010 Mar;26(3):571-88. doi: 10.1185/・・・
著者: Achim J Kaasch, Vance G Fowler, Siegbert Rieg, Gabriele Peyerl-Hoffmann, Hanna Birkholz, Martin Hellmich, Winfried V Kern, Harald Seifert
雑誌名: Clin Infect Dis. 2011 Jul 1;53(1):1-9. doi: 10.1093/cid/cir320.
Abstract/Text BACKGROUND: Infective endocarditis (IE) is a severe complication in patients with nosocomial Staphylococcus aureus bacteremia (SAB). We sought to develop and validate criteria to identify patients at low risk for the development of IE in whom transesophageal echocardiography (TEE) might be dispensable.
METHODS: Consecutive patients with nosocomial SAB from independent cohorts in Europe (Invasive S. aureus Infection Cohort [INSTINCT]) and North America (S. aureus Bacteremia Group [SABG]) were evaluated for the presence of clinical criteria predicting an increased risk for the development of IE (ie, prolonged bacteremia of >4 days' duration, presence of a permanent intracardiac device, hemodialysis dependency, spinal infection, and nonvertebral osteomyelitis). Patients were observed closely for clinical signs and symptoms of IE during hospitalization and a 3-month follow-up period.
RESULTS: IE was present in 13 (4.3%) of 304 patients in the INSTINCT cohort and in 40 (9.3%) of 432 patients in the SABG cohort. Within 14 days after the first positive blood culture result, echocardiography was performed in 39.8% and 57.4% of patients in the INSTINCT and SABG cohorts, respectively. In patients with IE, the most common clinical prediction criteria present were prolonged bacteremia (69.2% vs 90% for INSTINCT vs SABG, respectively) and presence of a permanent intracardiac device (53.8% vs 32.5%). In total, 13 of 13 patients in the INSTINCT cohort and 39 of 40 patients in the SABG cohort with documented IE fulfilled at least 1 criterion (sensitivity, 100% vs. 97.5%; negative predictive value, 100% vs 99.2%).
CONCLUSIONS: A simple criteria set for patients with nosocomial SAB can identify patients at low risk of IE. Patients who meet these criteria may not routinely require TEE.

© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
PMID 21653295  Clin Infect Dis. 2011 Jul 1;53(1):1-9. doi: 10.1093/cid・・・
著者: Riad Khatib, Mamta Sharma
雑誌名: Medicine (Baltimore). 2013 May;92(3):182-8. doi: 10.1097/MD.0b013e318294a710.
Abstract/Text Current Staphylococcus aureus bacteremia (SAB) practice guidelines stratify treatment duration according to the likelihood of complications and recommend transesophageal echocardiography (TEE) in all cases. The benefit of TEE in uncomplicated SAB has not been validated. We performed a retrospective analysis of TEE and transthoracic echocardiography (TTE) among hospitalized adults with SAB in 3 prior observational studies (2002-2003, 2005-2006, and 2008-2009). Echocardiograms were ordered at the attending physician's discretion. SAB cases were stratified into the following types: complicated (persistent bacteremia [duration ≥3 d], relapse, and/or secondary foci); device-associated (intracardiac prosthetic devices); suspected endocarditis (the presence of murmurs or emboli); and uncomplicated (bacteremia duration ≤2 d, no device and/or secondary foci). We encountered 960 SAB cases; 83 were excluded (57 death/transfer/discharge within 48 h; 19 contaminants/no treatment; 7 care withdrawn). TEE and TTE were performed within 0-28 days of SAB onset in 177 (20.2%) and 321 (36.6%) instances, respectively. TEE was positive (with signs of endocarditis) in 42/177 (23.7%) cases: 7/39 (17.9%) community associated and 35/138 (25.4%) health care associated. It was positive in 29/120 (24.2%) complicated, 3/11 (27.3%) device-associated, 9/15 (60.0%) suspected endocarditis, and 1/31 (3.2%) uncomplicated cases of SAB. TTE was positive in 25/321 (7.8%) cases of SAB, 1 was uncomplicated; it was negative in 20/30 (66.7%) TEE-positive cases. Follow-up of ≥100 days was possible in 282/361 (78.1%) uncomplicated SAB; many (46.8%) received ≤15 days of therapy. None of them had relapses or secondary foci.These findings suggest that echocardiography is dispensable in cases of uncomplicated community-associated and health care-associated SAB. It should be limited to subsets with clinical findings of endocarditis, persistence, intracardiac devices, secondary foci, and relapse. The cost effectiveness of TTE prior to TEE among these patients is unknown.

PMID 23619238  Medicine (Baltimore). 2013 May;92(3):182-8. doi: 10.109・・・
著者: Julie Paulsen, Erik Solligård, Jan Kristian Damås, Andrew DeWan, Bjørn Olav Åsvold, Michael B Bracken
雑誌名: Open Forum Infect Dis. 2016 Mar 1;3(2):ofw048. doi: 10.1093/ofid/ofw048. Epub 2016 Mar 1.
Abstract/Text Staphylococcus aureus is a common cause of severe bloodstream infection. We performed a systematic review to assess whether consultation with infectious disease specialists decreased all-cause mortality or rate of complications of S aureus bloodstream infections. The review also assessed parameters associated with the quality of management of the infection. We searched for eligible studies in PubMed, Embase, Scopus, and clinical trials.gov as well as the references of included studies. We identified 22 observational studies and 1 study protocol for a randomized trial. A meta-analysis was not performed because of the high risk of bias in the included studies. The outcomes are reported in a narrative review. Most included studies reported survival benefit, in the adjusted analysis. Recommended management strategies were carried out significantly more often among patients seen by an infectious disease specialist. Trials, such as cluster-randomized controlled trials, can more validly assess the studies at low risk of bias.

PMID 27047985  Open Forum Infect Dis. 2016 Mar 1;3(2):ofw048. doi: 10.・・・
著者: Monique Vogel, Roland P H Schmitz, Stefan Hagel, Mathias W Pletz, Nico Gagelmann, André Scherag, Peter Schlattmann, Frank M Brunkhorst
雑誌名: J Infect. 2016 Jan;72(1):19-28. doi: 10.1016/j.jinf.2015.09.037. Epub 2015 Oct 9.
Abstract/Text OBJECTIVE: Mortality and morbidity of Staphylococcus aureus bacteremia (SAB) still remains considerably high. We aimed to evaluate the impact of infectious disease consultation (IDC) on the management and outcomes of patients with SAB.
METHODS: We systematically searched 3 publication databases from inception to 31st May 2015 and reference lists of identified primary studies.
RESULTS: Our search returned 2874 reports, of which 18 fulfilled the inclusion criteria, accounting for 5337 patients. Overall 30-day mortality was 19.95% [95% CI 14.37-27.02] with a significant difference in favour of the IDC group (12.39% vs 26.07%) with a relative risk (RR) of 0.53 [95% CI 0.43-0.65]. 90-day mortality and relapse risk for SAB were also reduced significantly with RRs of 0.77 [95% CI 0.64-0.92] and 0.62 [95% CI 0.39-0.99], respectively. Both, the appropriateness of antistaphylococcal agent and treatment duration was improved by IDC (RR 1.14 [95% CI 1.08-1.20] and 1.85 [95% CI 1.39-2.46], respectively). Follow-up blood cultures and echocardiography were performed more frequently following IDC (RR 1.35 [95% CI 1.25-1.46] and 1.98 [95% CI 1.66-2.37], respectively).
CONCLUSIONS: Evidence-based clinical management enforced by IDC may improve outcome of patients with SAB. Well-designed cluster-randomized controlled trials are needed to confirm this finding from observational studies.

Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
PMID 26453841  J Infect. 2016 Jan;72(1):19-28. doi: 10.1016/j.jinf.201・・・
著者: E Forsblom, E Ruotsalainen, J Ollgren, A Järvinen
雑誌名: Clin Infect Dis. 2013 Feb;56(4):527-35. doi: 10.1093/cid/cis889. Epub 2012 Oct 19.
Abstract/Text BACKGROUND: Infectious disease specialist (IDS) consultation improves the outcome of Staphylococcus aureus bacteremia (SAB). Although telephone consultations constitute a substantial part of IDS consultations, their impact on treatment outcome lacks evaluation.
METHODS: We retrospectively followed 342 SAB episodes with 90-day follow-up, excluding 5 methicillin-resistant S. aureus SAB cases. Patients were grouped according to bedside, telephone, or no IDS consultation within the first week. Patients with fatal outcome within 3 days after onset of SAB were excluded to allow for the possibility of death occurring before IDS consultation.
RESULTS: Seventy-two percent of patients received bedside, 18% telephone, and 10% no IDS consultation. Patients with bedside consultation were less often treated in an intensive care unit during the first 3 days compared to those with telephone consultation (odds ratio [OR], 0.53; 95% confidence interval [CI], .29-.97; P = .037; 21% vs 34%), with no other initial differences between these groups. Patients with bedside consultation more often had deep infection foci localized as compared to patients with telephone consultation (OR, 3.11; 95% CI, 1.74-5.57; P < .0001; 78% vs 53%). Patients with bedside consultation had lower mortality than patients with telephone consultation at 7 days (OR, 0.09; 95% CI, .02-.49; P = .001; 1% vs 8%), at 28 days (OR, 0.27; 95% CI, .11-.65; P = .002; 5% vs 16%) and at 90 days (OR, 0.25; 95% CI, .13-.51; P < .0001; 9% vs 29%). Considering all prognostic markers, 90-day mortality for telephone-consultation patients was higher (OR, 2.31; CI, 95% 1.22-4.38; P = .01) as compared to bedside consultation.
CONCLUSIONS: Telephone IDS consultation is inferior to bedside IDS consultation.

PMID 23087397  Clin Infect Dis. 2013 Feb;56(4):527-35. doi: 10.1093/ci・・・
著者: Kevin W McConeghy, Susan C Bleasdale, Keith A Rodvold
雑誌名: Clin Infect Dis. 2013 Dec;57(12):1760-5. doi: 10.1093/cid/cit560. Epub 2013 Aug 28.
Abstract/Text The high prevalence of methicillin resistance among Staphylococcus aureus bacteremias leads to common use of vancomycin as empirical therapy. However, investigators have reported poor outcomes with vancomycin treatment for methicillin-susceptible Staphylococcus aureus bacteremia. We review the evidence supporting empirical combination of both vancomycin and a β-lactam agent for Staphylococcus aureus bacteremia. Vancomycin therapy for methicillin-susceptible Staphylococcus aureus bacteremia is associated with 2-3 times the risk of morbidity and mortality compared to an antistaphylococcal penicillin (oxacillin and nafcillin) or first-generation cephalosporin (cefazolin). De-escalation of empirical vancomycin to definitive β-lactam therapy still appears inferior to initial β-lactam therapy. Although there is no clinical trial supporting combination therapy, a scientific rationale for benefit exists and should be weighed against the risks (adverse events, antibiotic resistance, and cost) of additional pharmacotherapy. The empirical combination of vancomycin and a β-lactam (either nafcillin, oxacillin, or cefazolin) for staphylococcal bacteremia may improve infection-related clinical outcomes.

PMID 23985343  Clin Infect Dis. 2013 Dec;57(12):1760-5. doi: 10.1093/c・・・
著者: Jennifer S McDanel, Eli N Perencevich, Daniel J Diekema, Loreen A Herwaldt, Tara C Smith, Elizabeth A Chrischilles, Jeffrey D Dawson, Lan Jiang, Michihiko Goto, Marin L Schweizer
雑誌名: Clin Infect Dis. 2015 Aug 1;61(3):361-7. doi: 10.1093/cid/civ308. Epub 2015 Apr 21.
Abstract/Text BACKGROUND: Previous studies indicate that vancomycin is inferior to beta-lactams for treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections. However, it is unclear if this association is true for empiric and definitive therapy. Here, we compared beta-lactams with vancomycin for empiric and definitive therapy of MSSA bloodstream infections among patients admitted to 122 hospitals.
METHODS: This retrospective cohort study included all patients admitted to Veterans Affairs hospitals from 2003 to 2010 who had positive blood cultures for MSSA. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Empiric therapy was defined as starting treatment 2 days before and up to 4 days after the first MSSA blood culture was collected. Definitive therapy was defined as starting treatment between 4 and 14 days after the first positive blood culture was collected.
RESULTS: Patients who received empiric therapy with a beta-lactam had similar mortality compared with those who received vancomycin (HR, 1.03; 95% CI, .89-1.20) after adjusting for other factors. However, patients who received definitive therapy with a beta-lactam had 35% lower mortality compared with patients who received vancomycin (HR, 0.65; 95% CI, .52-.80) after controlling for other factors. The hazard of mortality decreased further for patients who received cefazolin or antistaphylococcal penicillins compared with vancomycin (HR, 0.57; 95% CI, .46-.71).
CONCLUSIONS: For patients with MSSA bloodstream infections, beta-lactams are superior to vancomycin for definitive therapy but not for empiric treatment. Patients should receive beta-lactams for definitive therapy, specifically antistaphylococcal penicillins or cefazolin.

Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
PMID 25900170  Clin Infect Dis. 2015 Aug 1;61(3):361-7. doi: 10.1093/c・・・
著者: Stryjewski Martin E ME, Szczech Lynda A LA, Benjamin Daniel K DK Jr, Inrig Jula K JK, Kanafani Zeina A ZA, Engemann John J JJ, Chu Vivian H VH, Joyce Maria J MJ, Reller L Barth LB, Corey G Ralph GR, Fowler Vance G VG Jr
雑誌名: Clin Infect Dis. 2007 Jan 15;44(2):190-6. doi: 10.1086/510386. Epub 2006 Dec 8.
Abstract/Text BACKGROUND: Because of its ease of dosing, vancomycin is commonly used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients undergoing long-term hemodialysis. Clinical outcomes resulting from such a therapeutic strategy have not been well defined.
METHODS: We prospectively identified patients undergoing long-term hemodialysis who received a diagnosis of MSSA bacteremia. Clinical outcomes were grouped according to the predominant antibiotic received during their therapy (vancomycin or a first-generation cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent infection) was determined at 12 weeks after the initial positive blood culture results. A multivariable analysis was used to adjust for confounders.
RESULTS: During an 84-month period, 123 hemodialysis-dependent patients with MSSA bacteremia were identified. Patients receiving vancomycin (n=77) tended to be younger (51 vs. 57 years; P=.06) and had a lower rates of metastatic complications at presentation (11.7% vs. 36.7%; P=.001) than did those receiving cefazolin (n=46). The 2 groups were similar with regard to Acute Physiology and Chronic Health Evaluation II scores, comorbidities, source of infection, type of hemodialysis access, and access removal rates. Treatment failure was more common among patients receiving vancomycin (31.2% vs. 13%; P=.02). In the multivariable analysis, factors independently associated with treatment failure included vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15-13.45) and retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval, 1.89-13.76).
CONCLUSIONS: Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to beta-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.

PMID 17173215  Clin Infect Dis. 2007 Jan 15;44(2):190-6. doi: 10.1086/・・・
著者: Marin L Schweizer, Jon P Furuno, Anthony D Harris, J Kristie Johnson, Michelle D Shardell, Jessina C McGregor, Kerri A Thom, Sara E Cosgrove, George Sakoulas, Eli N Perencevich
雑誌名: BMC Infect Dis. 2011 Oct 19;11:279. doi: 10.1186/1471-2334-11-279. Epub 2011 Oct 19.
Abstract/Text BACKGROUND: The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.
METHODS: This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin.
RESULTS: 267 patients were included; 14% (38/267) received nafcillin or cefazolin, 51% (135/267) received both vancomycin and either nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin.
CONCLUSIONS: Receipt of nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of nafcillin or cefazolin in the treatment of MSSA bacteremia.

PMID 22011388  BMC Infect Dis. 2011 Oct 19;11:279. doi: 10.1186/1471-2・・・
著者: R Khatib, S Saeed, M Sharma, K Riederer, M G Fakih, L B Johnson
雑誌名: Eur J Clin Microbiol Infect Dis. 2006 Mar;25(3):181-5. doi: 10.1007/s10096-006-0096-0.
Abstract/Text The study presented here investigated the impact of initial antibiotic choice (beta-lactams vs vancomycin) on the outcome of 342 patients with Staphylococcus aureus bacteremia (50.9% with methicillin-resistant isolates) encountered between 1 January 2002 and 30 June 2003. Initial antibiotics were inappropriate (beta-lactams) in 60 (34.5%) methicillin-resistant cases and suboptimal (vancomycin) in 62 (36.9%) methicillin-susceptible cases. Time to effective antibiotic therapy was longer in methicillin-resistant cases (25.5+/-28.6 vs 9.6+/-16.6 h; p<0.0005). All-cause in-hospital mortality was higher with inappropriate therapy (35.0 vs 20.9%; p=0.02). Initial vancomycin treatment was associated with a higher incidence of delayed clearance (>or=3 days) of methicillin-susceptible bacteremia (56.3 vs 37.0%; p=0.03). The results indicate inappropriate initial therapy is associated with higher in-hospital mortality and initial vancomycin may delay clearance.

PMID 16505987  Eur J Clin Microbiol Infect Dis. 2006 Mar;25(3):181-5. ・・・
著者: Thomas P Lodise, Peggy S McKinnon, Donald P Levine, Michael J Rybak
雑誌名: Antimicrob Agents Chemother. 2007 Oct;51(10):3731-3. doi: 10.1128/AAC.00101-07. Epub 2007 Jul 30.
Abstract/Text This study compares beta-lactam and vancomycin among intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus. Patients who received vancomycin had higher infection-related mortality, even if they were switched to beta-lactam once culture results became available; this relationship persisted after logistic regression analysis controlling for clinical characteristics.

PMID 17664322  Antimicrob Agents Chemother. 2007 Oct;51(10):3731-3. do・・・
著者: Joshua S Davis, Archana Sud, Matthew V N O'Sullivan, James O Robinson, Patricia E Ferguson, Hong Foo, Sebastiaan J van Hal, Anna P Ralph, Benjamin P Howden, Paula M Binks, Adrienne Kirby, Steven Y C Tong, Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group, Australasian Society for Infectious Diseases Clinical Research Network
雑誌名: Clin Infect Dis. 2016 Jan 15;62(2):173-80. doi: 10.1093/cid/civ808. Epub 2015 Sep 8.
Abstract/Text BACKGROUND: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking.
METHODS: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days.
RESULTS: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity.
CONCLUSIONS: Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).

© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PMID 26349552  Clin Infect Dis. 2016 Jan 15;62(2):173-80. doi: 10.1093・・・

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