今日の臨床サポート

市中肺炎

著者: 福地貴彦 自治医科大学附属さいたま医療センター 総合診療科

監修: 具芳明 東京医科歯科大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2021/03/24
参考ガイドライン:
  1. 米国胸部学会(ATS)/米国感染症学会(IDSA):IDSA/ATSガイドライン2019
患者向け説明資料

概要・推奨   

  1. 市中肺炎を疑った際、COVID-19の有病率が高い時期・地域の場合にはまず第一にCOVID-19の除外を行う(推奨度1)。
  1. 市中肺炎と診断したら、種々のガイドラインに則って重症度を算出し、外来/一般病棟/ICUのいずれでどのように治療するかを検討することは、おそらく推奨される(推奨度1)。
  1. 秋から冬にかけての市中肺炎患者に対して、未接種であれば肺炎治癒後にインフルエンザワクチンを接種することは、おそらく推奨される(推奨度2)。
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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:
福地貴彦 : 特に申告事項無し[2021年]
監修:具芳明 : 特に申告事項無し[2021年]

改訂のポイント:
  1. ACIPの推奨に従い、プレベナーの記載を変更した。
  1. COVID-19のパンデミックに伴い、記載を追加した。

病態・疫学・診察

疾患情報  
  1. 市中肺炎とは、通常の社会生活を送っている人が医療機関以外の場所で感染することで起きる肺炎であり、院内肺炎とは区別される。つまり、感染発症90日前に2日以上の入院や抗菌薬の使用や、介護施設や透析施設などの医療機関からの入院などに該当しない患者に起こった肺炎である。
  1. 日本での肺炎受療率は人口10万対30 で、死亡率は人口10万対70。死因順位は2011年より第3位である。受療率、罹患率ともに高齢になるにしたがい急増し、85歳以上の男性では死因第2位、90歳以上の男性では第1位 となる。
  1. 発熱、咳、呼吸困難が典型的症状だが、高齢者や免疫抑制患者では訴えが不明瞭なことも多い。
  1. 上記が一般的な市中肺炎の考え方であるが、2020年のCOVID-19の大流行に伴い、発想そのものを大きく転換せざるを得なくなった。COVID-19の有病率が高い場合、まず第一にCOVID-19を疑って診療活動を開始する(COVID-19(新型コロナウイルス感染症)の項を参照)。
問診・診察のポイント  
  1. 重症度分類のためにバイタルサインを測定する。特に呼吸数が予後とも相関するため重要である。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: R M Blázquez, F J Espinosa, C M Martínez-Toldos, L Alemany, M C García-Orenes, M Segovia
雑誌名: Eur J Clin Microbiol Infect Dis. 2005 Jul;24(7):488-91. doi: 10.1007/s10096-005-1361-3.
Abstract/Text Presented here are the results of Legionella urinary antigen testing correlated with patient characteristics and severity of pneumonia (Fine score) in 295 patients diagnosed with Legionella pneumonia in connection with a large outbreak in Murcia, Spain. Overall, the sensitivity of the urinary antigen test was 47.7% (141/295). A statistically significant association was found between the clinical severity of pneumonia and test sensitivity; 85.7% for patients with severe pneumonia versus 37.9% for patients with mild pneumonia (risk ratio, 2.3). Variables significantly associated with test positivity in multivariate analysis were as follows: pre-existing pulmonary disease, body temperature >40 degrees C, leukocytosis and multilobar infiltrates. Patients with mild pneumonia may go undiagnosed if the urinary antigen test is used alone.

PMID 15997369  Eur J Clin Microbiol Infect Dis. 2005 Jul;24(7):488-91.・・・
著者: Joshua P Metlay, Grant W Waterer, Ann C Long, Antonio Anzueto, Jan Brozek, Kristina Crothers, Laura A Cooley, Nathan C Dean, Michael J Fine, Scott A Flanders, Marie R Griffin, Mark L Metersky, Daniel M Musher, Marcos I Restrepo, Cynthia G Whitney
雑誌名: Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST.
Abstract/Text Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.

PMID 31573350  Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. d・・・
著者: F Arancibia, S Ewig, J A Martinez, M Ruiz, T Bauer, M A Marcos, J Mensa, A Torres
雑誌名: Am J Respir Crit Care Med. 2000 Jul;162(1):154-60. doi: 10.1164/ajrccm.162.1.9907023.
Abstract/Text The aim of the study was to determine the causes and prognostic implications of antimicrobial treatment failures in patients with nonresponding and progressive life-threatening, community-acquired pneumonia. Forty-nine patients hospitalized with a presumptive diagnosis of community-acquired pneumonia during a 16-mo period, failure to respond to antimicrobial treatment, and documented repeated microbial investigation >/= 72 h after initiation of in-hospital antimicrobial treatment were recorded. A definite etiology of treatment failure could be established in 32 of 49 (65%) patients, and nine additional patients (18%) had a probable etiology. Treatment failures were mainly infectious in origin and included primary, persistent, and nosocomial infections (n = 10 [19%], 13 [24%], and 11 [20%] of causes, respectively). Definite but not probable persistent infections were mostly due to microbial resistance to the administered initial empiric antimicrobial treatment. Nosocomial infections were particularly frequent in patients with progressive pneumonia. Definite persistent infections and nosocomial infections had the highest associated mortality rates (75 and 88%, respectively). Nosocomial pneumonia was the only cause of treatment failure independently associated with death in multivariate analysis (RR, 16.7; 95% CI, 1.4 to 194.9; p = 0.03). We conclude that the detection of microbial resistance and the diagnosis of nosocomial pneumonia are the two major challenges in hospitalized patients with community-acquired pneumonia who do not respond to initial antimicrobial treatment. In order to establish these potentially life-threatening etiologies, a regular microbial reinvestigation seems mandatory for all patients presenting with antimicrobial treatment failures.

PMID 10903235  Am J Respir Crit Care Med. 2000 Jul;162(1):154-60. doi:・・・
著者: Beatriz Rosón, Jordi Carratalà, Núria Fernández-Sabé, Fe Tubau, Frederic Manresa, Francesc Gudiol
雑誌名: Arch Intern Med. 2004 Mar 8;164(5):502-8. doi: 10.1001/archinte.164.5.502.
Abstract/Text BACKGROUND: Early failure is a matter of great concern in the treatment of community-acquired pneumonia. However, information on its causes and risk factors is lacking.
METHODS: Observational analysis of a prospective series of 1383 nonimmunosuppressed hospitalized adults with community-acquired pneumonia. Early failure was defined as lack of response or worsening of clinical or radiologic status at 48 to 72 hours requiring changes in antibiotic therapy or invasive procedures. Concordance of antimicrobial therapy was examined for cases with an etiologic diagnosis.
RESULTS: At 48 to 72 hours, 238 patients (18%) remained febrile, but most of them responded without further changes in antibiotic therapy. Eighty-one patients (6%) had early failure. The main causes of early failure were progressive pneumonia (n = 54), pleural empyema (n = 18), lack of response (n = 13), and uncontrolled sepsis (n = 9). Independent factors associated with early failure were older age (>65 years) (odds ratio [OR], 0.35), multilobar pneumonia (OR, 1.81), Pneumonia Severity Index score greater than 90 (OR, 2.75), Legionella pneumonia (OR, 2.71), gram-negative pneumonia (OR, 4.34), and discordant antimicrobial therapy (OR, 2.51). Compared with treatment responders, early failures had significantly higher rates of complications (58% vs 24%) and overall mortality (27% vs 4%) (P<.001 for both).
CONCLUSIONS: Early failure is infrequent but is associated with high morbidity and mortality rates. Its detection and management require careful clinical assessment. Most cases occur because of inadequate host-pathogen responses. Discordant therapy is a less frequent cause of failure, which may be preventable by rational application of the current antibiotic guidelines.

PMID 15006826  Arch Intern Med. 2004 Mar 8;164(5):502-8. doi: 10.1001/・・・
著者: W S Lim, S V Baudouin, R C George, A T Hill, C Jamieson, I Le Jeune, J T Macfarlane, R C Read, H J Roberts, M L Levy, M Wani, M A Woodhead, Pneumonia Guidelines Committee of the BTS Standards of Care Committee
雑誌名: Thorax. 2009 Oct;64 Suppl 3:iii1-55. doi: 10.1136/thx.2009.121434.
Abstract/Text
PMID 19783532  Thorax. 2009 Oct;64 Suppl 3:iii1-55. doi: 10.1136/thx.2・・・
著者: Graham D Mills, Michael R Oehley, Bruce Arrol
雑誌名: BMJ. 2005 Feb 26;330(7489):456. doi: 10.1136/bmj.38334.591586.82. Epub 2005 Jan 31.
Abstract/Text OBJECTIVE: To systematically compare beta lactam antibiotics with antibiotics active against atypical pathogens in the management of community acquired pneumonia.
DATA SOURCES: Medline, Embase, Cochrane register of controlled trials, international conference proceedings, drug registration authorities, and pharmaceutical companies. Review methods Double blind randomised controlled monotherapy trials comparing beta lactam antibiotics with antibiotics active against atypical pathogens in adults with community acquired pneumonia. Primary outcome was failure to achieve clinical cure or improvement.
RESULTS: 18 trials totalling 6749 participants were identified, with most patients having mild to moderate community acquired pneumonia. The summary relative risk for treatment failure in all cause community acquired pneumonia showed no advantage of antibiotics active against atypical pathogens over beta lactam antibiotics (0.97, 95% confidence interval 0.87 to 1.07). Subgroup analysis was undertaken in those with a specific diagnosis involving atypical pathogens. We found a significantly lower failure rate in patients with Legionella species who were treated with antibiotics active against atypical pathogens (0.40, 0.19 to 0.85). Equivalence was seen for Mycoplasma pneumoniae (0.60, 0.31 to 1.17) and Chlamydia pneumoniae (2.32, 0.67 to 8.03).
CONCLUSIONS: Evidence is lacking that clinical outcomes are improved by using antibiotics active against atypical pathogens in all cause non-severe community acquired pneumonia. Although such antibiotics were superior in the management of patients later shown to have legionella related pneumonia, this pathogen was rarely responsible for pneumonia within the included trials. beta lactam agents should remain the antibiotics of initial choice in adults with non-severe community acquired pneumonia.

PMID 15684024  BMJ. 2005 Feb 26;330(7489):456. doi: 10.1136/bmj.38334.・・・
著者: Takaya Maruyama, Takao Fujisawa, Masataka Okuno, Hirokazu Toyoshima, Kiyoyuki Tsutsui, Hikaru Maeda, Hisamichi Yuda, Masamichi Yoshida, Hiroyasu Kobayashi, Osamu Taguchi, Esteban C Gabazza, Yoshiyuki Takei, Naoyuki Miyashita, Toshiaki Ihara, Veronica Brito, Michael S Niederman
雑誌名: Clin Infect Dis. 2013 Nov;57(10):1373-83. doi: 10.1093/cid/cit571. Epub 2013 Sep 2.
Abstract/Text BACKGROUND: Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain.
METHODS: We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321).
RESULTS: MDR pathogens were more common (15.3% vs 0.8%, P < .001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, P < .001); methicillin-resistant S. aureus (6.9% vs 0%, P = .003); Enterobacteriaceae (7.8% vs 2.4%, P = .037); and Pseudomonas aeruginosa (6.9% vs 0.8%, P = .01). Using the proposed algorithm, HCAP patients with ≥2 MDR risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0-1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P < .001). In total, 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. Thirty-day mortality was significantly higher for HCAP than for CAP (13.7% vs 5.6%, P = .017), but among HCAP patients with 0-1 MDR risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P = .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0).
CONCLUSIONS: Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy.
CLINICAL TRIALS REGISTRATION: Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

PMID 23999080  Clin Infect Dis. 2013 Nov;57(10):1373-83. doi: 10.1093/・・・
著者: Anat Stern, Keren Skalsky, Tomer Avni, Elena Carrara, Leonard Leibovici, Mical Paul
雑誌名: Cochrane Database Syst Rev. 2017 Dec 13;12:CD007720. doi: 10.1002/14651858.CD007720.pub3. Epub 2017 Dec 13.
Abstract/Text BACKGROUND: Pneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011.
OBJECTIVES: To assess the efficacy and safety of corticosteroids in the treatment of pneumonia.
SEARCH METHODS: We searched the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3 March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel-Haenszel fixed-effect model when possible.
MAIN RESULTS: We included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.All trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93).
AUTHORS' CONCLUSIONS: Corticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.

PMID 29236286  Cochrane Database Syst Rev. 2017 Dec 13;12:CD007720. do・・・
著者: Reed A C Siemieniuk, Maureen O Meade, Pablo Alonso-Coello, Matthias Briel, Nathan Evaniew, Manya Prasad, Paul E Alexander, Yutong Fei, Per O Vandvik, Mark Loeb, Gordon H Guyatt
雑誌名: Ann Intern Med. 2015 Oct 6;163(7):519-28. doi: 10.7326/M15-0715.
Abstract/Text BACKGROUND: Community-acquired pneumonia (CAP) is common and often severe.
PURPOSE: To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP.
DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through 24 May 2015.
STUDY SELECTION: Randomized trials of systemic corticosteroids in hospitalized adults with CAP.
DATA EXTRACTION: Two reviewers independently extracted study data and assessed risk of bias. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation system by consensus among the authors.
DATA SYNTHESIS: The median age was typically in the 60s, and approximately 60% of patients were male. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality (12 trials; 1974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%; moderate certainty), need for mechanical ventilation (5 trials; 1060 patients; RR, 0.45 [CI, 0.26 to 0.79]; RD, 5.0%; moderate certainty), and the acute respiratory distress syndrome (4 trials; 945 patients; RR, 0.24 [CI, 0.10 to 0.56]; RD, 6.2%; moderate certainty). They also decreased time to clinical stability (5 trials; 1180 patients; mean difference, -1.22 days [CI, -2.08 to -0.35 days]; high certainty) and duration of hospitalization (6 trials; 1499 patients; mean difference, -1.00 day [CI, -1.79 to -0.21 days]; high certainty). Adjunctive corticosteroids increased frequency of hyperglycemia requiring treatment (6 trials; 1534 patients; RR, 1.49 [CI, 1.01 to 2.19]; RD, 3.5%; high certainty) but did not increase frequency of gastrointestinal hemorrhage.
LIMITATIONS: There were few events and trials for many outcomes. Trials often excluded patients at high risk for adverse events.
CONCLUSION: For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day.
PRIMARY FUNDING SOURCE: None.

PMID 26258555  Ann Intern Med. 2015 Oct 6;163(7):519-28. doi: 10.7326/・・・
著者: Kelly E Dooley, Jonathan Golub, Fernando S Goes, William G Merz, Timothy R Sterling
雑誌名: Clin Infect Dis. 2002 Jun 15;34(12):1607-12. doi: 10.1086/340618. Epub 2002 May 23.
Abstract/Text Fluoroquinolones, which are widely used to treat community-acquired pneumonia, also have excellent in vitro activity against Mycobacterium tuberculosis. A retrospective cohort study was conducted among adults with culture-confirmed tuberculosis to assess the effect of empiric fluoroquinolone therapy on delays in the treatment of tuberculosis. Sixteen (48%) of 33 patients received fluoroquinolones for presumed bacterial pneumonia before tuberculosis was diagnosed and treated. There were no differences between the group who did and the group who did not receive fluoroquinolones, except that patients who received fluoroquinolones were more likely to present with shortness of breath. Among patients treated empirically with fluoroquinolones, the median time between presentation to the hospital and initiation of antituberculosis treatment was 21 days (interquartile range, 5-32 days); among those who were not, it was 5 days (interquartile range, 1-16 days; P=.04). Initial empiric therapy with a fluoroquinolone was associated with a delay in the initiation of appropriate antituberculosis treatment.

PMID 12032896  Clin Infect Dis. 2002 Jun 15;34(12):1607-12. doi: 10.10・・・
著者: Jan Jelrik Oosterheert, Marc J M Bonten, Margriet M E Schneider, Erik Buskens, Jan-Willem J Lammers, Willem M N Hustinx, Mark H H Kramer, Jan M Prins, Peter H Th J Slee, Karin Kaasjager, Andy I M Hoepelman
雑誌名: BMJ. 2006 Dec 9;333(7580):1193. doi: 10.1136/bmj.38993.560984.BE. Epub 2006 Nov 7.
Abstract/Text OBJECTIVES: To compare the effectiveness of an early switch to oral antibiotics with the standard 7 day course of intravenous antibiotics in severe community acquired pneumonia.
DESIGN: Multicentre randomised controlled trial.
SETTING: Five teaching hospitals and 2 university medical centres in the Netherlands.
PARTICIPANTS: 302 patients in non-intensive care wards with severe community acquired pneumonia. 265 patients fulfilled the study requirements.
INTERVENTION: Three days of treatment with intravenous antibiotics followed, when clinically stable, by oral antibiotics or by 7 days of intravenous antibiotics.
MAIN OUTCOME MEASURES: Clinical cure and length of hospital stay.
RESULTS: 302 patients were randomised (mean age 69.5 (standard deviation 14.0), mean pneumonia severity score 112.7 (26.0)). 37 patients were excluded from analysis because of early dropout before day 3, leaving 265 patients for intention to treat analysis. Mortality at day 28 was 4% in the intervention group and 6% in the control group (mean difference 2%, 95% confidence interval -3% to 8%). Clinical cure was 83% in the intervention group and 85% in the control group (2%, -7% to 10%). Duration of intravenous treatment and length of hospital stay were reduced in the intervention group, with mean differences of 3.4 days (3.6 (1.5) v 7.0 (2.0) days; 2.8 to 3.9) and 1.9 days (9.6 (5.0) v 11.5 (4.9) days; 0.6 to 3.2), respectively.
CONCLUSIONS: Early switch from intravenous to oral antibiotics in patients with severe community acquired pneumonia is safe and decreases length of hospital stay by 2 days.
TRIAL REGISTRATION: Clinical Trials NCT00273676 [ClinicalTrials.gov].

PMID 17090560  BMJ. 2006 Dec 9;333(7580):1193. doi: 10.1136/bmj.38993.・・・
著者: Seema Jain, Wesley H Self, Richard G Wunderink, Sherene Fakhran, Robert Balk, Anna M Bramley, Carrie Reed, Carlos G Grijalva, Evan J Anderson, D Mark Courtney, James D Chappell, Chao Qi, Eric M Hart, Frank Carroll, Christopher Trabue, Helen K Donnelly, Derek J Williams, Yuwei Zhu, Sandra R Arnold, Krow Ampofo, Grant W Waterer, Min Levine, Stephen Lindstrom, Jonas M Winchell, Jacqueline M Katz, Dean Erdman, Eileen Schneider, Lauri A Hicks, Jonathan A McCullers, Andrew T Pavia, Kathryn M Edwards, Lyn Finelli, CDC EPIC Study Team
雑誌名: N Engl J Med. 2015 Jul 30;373(5):415-27. doi: 10.1056/NEJMoa1500245. Epub 2015 Jul 14.
Abstract/Text BACKGROUND: Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radiographically and with the use of current laboratory diagnostic tests are needed.
METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among adults 18 years of age or older in five hospitals in Chicago and Nashville. Patients with recent hospitalization or severe immunosuppression were excluded. Blood, urine, and respiratory specimens were systematically collected for culture, serologic testing, antigen detection, and molecular diagnostic testing. Study radiologists independently reviewed chest radiographs. We calculated population-based incidence rates of community-acquired pneumonia requiring hospitalization according to age and pathogen.
RESULTS: From January 2010 through June 2012, we enrolled 2488 of 3634 eligible adults (68%). Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. Among 2259 patients who had radiographic evidence of pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 853 (38%): one or more viruses in 530 (23%), bacteria in 247 (11%), bacterial and viral pathogens in 59 (3%), and a fungal or mycobacterial pathogen in 17 (1%). The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%). The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). For each pathogen, the incidence increased with age.
CONCLUSIONS: The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults. Despite current diagnostic tests, no pathogen was detected in the majority of patients. Respiratory viruses were detected more frequently than bacteria. (Funded by the Influenza Division of the National Center for Immunizations and Respiratory Diseases.).

PMID 26172429  N Engl J Med. 2015 Jul 30;373(5):415-27. doi: 10.1056/N・・・
著者: Naomi J Gadsby, Clark D Russell, Martin P McHugh, Harriet Mark, Andrew Conway Morris, Ian F Laurenson, Adam T Hill, Kate E Templeton
雑誌名: Clin Infect Dis. 2016 Apr 1;62(7):817-823. doi: 10.1093/cid/civ1214. Epub 2016 Jan 7.
Abstract/Text BACKGROUND: The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP.
METHODS: Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns.
RESULTS: Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients.
CONCLUSIONS: Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.
PMID 26747825  Clin Infect Dis. 2016 Apr 1;62(7):817-823. doi: 10.1093・・・
著者: S A Moberley, J Holden, D P Tatham, R M Andrews
雑誌名: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000422. doi: 10.1002/14651858.CD000422.pub2. Epub 2008 Jan 23.
Abstract/Text BACKGROUND: Diseases caused by Streptococcus pneumoniae(S. pneumoniae) continue to cause substantial morbidity and mortality throughout the world. Whilst pneumococcal polysaccharide vaccines (PPV) have the potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within different populations is uncertain.
OBJECTIVES: To assess the effectiveness of PPV in preventing disease or death in adults. Adverse events were not assessed.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2); MEDLINE (January 1966 to June 2007); and EMBASE (1974 to June 2007).
SELECTION CRITERIA: A) Randomised controlled trials (RCTs) comparing PPV with placebo, control vaccines, or no intervention.B) Non-RCTs assessing PPV effectiveness against invasive pneumococcal disease (IPD).
DATA COLLECTION AND ANALYSIS: A) RCTs: trial quality assessment was conducted by two review authors and data extracted by three authors; odds ratios (OR) and 95% confidence intervals (CI) were estimated using a random-effects model.B) Non-RCTs: study quality, including measures to control for confounding, was assessed and data extracted by two review authors; OR and 95% CI were calculated using a random-effects model following the conversion of each study outcome to a log OR and standard error.
MAIN RESULTS: Twenty-two studies met our inclusion criteria (15 RCTs involving 48,656 participants and 7 non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.15 to 0.46; random-effects model, I-squared (I(2)) = 0%). Efficacy against all cause pneumonia was inconclusive with substantial statistical heterogeneity (OR 0.71, 95% CI 0.52 to 0.97; random-effects model, I(2) = 87.3%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.87, 95% CI 0.69 to 1.10; random-effects model, I(2) = 75.3%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness but the difference was not statistically significant. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I(2) = 31.4%).
AUTHORS' CONCLUSIONS: This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide compelling evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.

PMID 18253977  Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000422. d・・・
著者: Miwako Kobayashi, Nancy M Bennett, Ryan Gierke, Olivia Almendares, Matthew R Moore, Cynthia G Whitney, Tamara Pilishvili
雑誌名: MMWR Morb Mortal Wkly Rep. 2015 Sep 4;64(34):944-7. doi: 10.15585/mmwr.mm6434a4. Epub 2015 Sep 4.
Abstract/Text Two pneumococcal vaccines are currently licensed for use in the United States: the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc.]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). The Advisory Committee on Immunization Practices (ACIP) currently recommends that a dose of PCV13 be followed by a dose of PPSV23 in all adults aged ≥65 years who have not previously received pneumococcal vaccine and in persons aged ≥2 years who are at high risk for pneumococcal disease because of underlying medical conditions (Table) (1-4). The recommended intervals between PCV13 and PPSV23 given in series differ by age and risk group and the order in which the two vaccines are given (1-4).

PMID 26334788  MMWR Morb Mortal Wkly Rep. 2015 Sep 4;64(34):944-7. doi・・・
著者: J P Nuorti, J C Butler, M M Farley, L H Harrison, A McGeer, M S Kolczak, R F Breiman
雑誌名: N Engl J Med. 2000 Mar 9;342(10):681-9. doi: 10.1056/NEJM200003093421002.
Abstract/Text BACKGROUND: Approximately half of otherwise healthy adults with invasive pneumococcal disease are cigarette smokers. We conducted a population-based case-control study to assess the importance of cigarette smoking and other factors as risk factors for pneumococcal infections.
METHODS: We identified immunocompetent patients who were 18 to 64 years old and who had invasive pneumococcal disease (as defined by the isolation of Streptococcus pneumoniae from a normally sterile site) by active surveillance of laboratories in metropolitan Atlanta, Baltimore, and Toronto. Telephone interviews were conducted with 228 patients and 301 control subjects who were reached by random-digit dialing.
RESULTS: Fifty-eight percent of the patients and 24 percent of the control subjects were current smokers. Invasive pneumococcal disease was associated with cigarette smoking (odds ratio, 4.1; 95 percent confidence interval, 2.4 to 7.3) and with passive smoking among nonsmokers (odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.1) after adjustment by logistic-regression analysis for age, study site, and independent risk factors such as male sex, black race, chronic illness, low level of education, and living with young children who were in day care. There were dose-response relations for the current number of cigarettes smoked per day, pack-years of smoking, and time since quitting. The adjusted population attributable risk was 51 percent for cigarette smoking, 17 percent for passive smoking, and 14 percent for chronic illness.
CONCLUSIONS: Cigarette smoking is the strongest independent risk factor for invasive pneumococcal disease among immunocompetent, nonelderly adults. Because of the high prevalence of smoking and the large population attributable risk, programs to reduce both smoking and exposure to environmental tobacco smoke have the potential to reduce the incidence of pneumococcal disease.

PMID 10706897  N Engl J Med. 2000 Mar 9;342(10):681-9. doi: 10.1056/NE・・・
著者: B J Marston, H B Lipman, R F Breiman
雑誌名: Arch Intern Med. 1994 Nov 14;154(21):2417-22.
Abstract/Text BACKGROUND: To augment available information about the epidemiology of legionnaires' disease, we analyzed data reported to the passive surveillance system at the Centers for Disease Control and Prevention, Atlanta, Ga, from 1980 through 1989.
METHODS: Risk of disease associated with specific demographic characteristics and health conditions was calculated by comparing the surveillance group with the US population. Risk of death was calculated using multivariate logistic regression models.
RESULTS: A diagnosis of legionnaires' disease was confirmed on the basis of clinical and laboratory criteria for 3254 patients. Disease rates did not vary by year, but were higher in the northern states and during the summer. Legionella pneumophila, serogroup 1, constituted 71.5% of fully identified isolates. This study confirmed previously identified risk factors for legionnaires' disease. In addition, a markedly elevated risk was identified for persons with acquired immunodeficiency syndrome (rate ratio, 41.9; 95% confidence interval, 12.9, 71.0), or hematologic malignancy (rate ratio, 22.4; 95% confidence interval, 19.0, 25.9). Likelihood of death was increased in patients who were elderly or male; those with hospital-acquired infection, renal disease, malignancy, or immunosuppression; and those from whom L pneumophila, serogroup 6, was isolated.
CONCLUSIONS: Infection with Legionella remains an important cause of disease and death in the United States. Diagnosis and treatment of legionnaires' disease should be targeted at patients at increased risk for illness and complications due to Legionella infection. Diagnostic tests for legionnaires' disease based on species other than L pneumophila, serogroup 1, should be developed and tested. Recommendations for prevention of legionnaires' disease should be focused on settings where there are persons at greatest risk for illness or serious outcome.

PMID 7979837  Arch Intern Med. 1994 Nov 14;154(21):2417-22.
著者: Jonathan Z Li, Lisa G Winston, Dan H Moore, Stephen Bent
雑誌名: Am J Med. 2007 Sep;120(9):783-90. doi: 10.1016/j.amjmed.2007.04.023.
Abstract/Text PURPOSE: There is little consensus on the most appropriate duration of antibiotic treatment for community-acquired pneumonia. The goal of this study is to systematically review randomized controlled trials comparing short-course and extended-course antibiotic regimens for community-acquired pneumonia.
METHODS: We searched MEDLINE, Embase, and CENTRAL, and reviewed reference lists from 1980 through June 2006. Studies were included if they were randomized controlled trials that compared short-course (7 days or less) versus extended-course (>7 days) antibiotic monotherapy for community-acquired pneumonia in adults. The primary outcome measure was failure to achieve clinical improvement.
RESULTS: We found 15 randomized controlled trials matching our inclusion and exclusion criteria comprising 2796 total subjects. Short-course regimens primarily studied the use of azithromycin (n=10), but trials examining beta-lactams (n=2), fluoroquinolones (n=2), and ketolides (n=1) were found as well. Of the extended-course regimens, 3 studies utilized the same antibiotic, whereas 9 involved an antibiotic of the same class. Overall, there was no difference in the risk of clinical failure between the short-course and extended-course regimens (0.89, 95% confidence interval [CI], 0.78-1.02). In addition, there were no differences in the risk of mortality (0.81, 95% CI, 0.46-1.43) or bacteriologic eradication (1.11, 95% CI, 0.76-1.62). In subgroup analyses, there was a trend toward favorable clinical efficacy for the short-course regimens in all antibiotic classes (range of relative risk, 0.88-0.94).
CONCLUSIONS: The available studies suggest that adults with mild to moderate community-acquired pneumonia can be safely and effectively treated with an antibiotic regimen of 7 days or less. Reduction in patient exposure to antibiotics may limit the increasing rates of antimicrobial drug resistance, decrease cost, and improve patient adherence and tolerability.

PMID 17765048  Am J Med. 2007 Sep;120(9):783-90. doi: 10.1016/j.amjmed・・・
著者: George Dimopoulos, Dimitrios K Matthaiou, Drosos E Karageorgopoulos, Alexandros P Grammatikos, Zoe Athanassa, Matthew E Falagas
雑誌名: Drugs. 2008;68(13):1841-54.
Abstract/Text BACKGROUND: The evidence for traditionally recommended 7- to 14-day duration of antibacterial therapy for community-acquired pneumonia (CAP) is not well established.
OBJECTIVES: We endeavoured to assess the effectiveness and safety of shorter than traditionally recommended antibacterial therapy for CAP.
METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing short- (< or = 7 days) versus long- (> or = 2 days difference) course therapy for CAP with the same antibacterial regimens, in the same daily dosages.
RESULTS: Five RCTs involving adults (including outpatients and inpatients who did not require intensive care) and two RCTs involving children (aged 2-59 months, residing in developing countries) were included. All RCTs were double-blind and assessed patients with CAP of mild to moderate severity. No differences were found between short- (adults 3-7 days; children 3 days) and long- (adults 7-10 days; children 5 days) course regimens (adults - amoxicillin, cefuroxime, ceftriaxone, telithromycin and gemifloxacin; children - amoxicillin) regarding clinical success at end-of-therapy (six RCTs; 5107 patients [1095 adults, 4012 children]; fixed-effect model [FEM]; odds ratio [OR] = 0.89; 95% CI 0.74, 1.07), clinical success at late follow-up, microbiological success, relapses, mortality (seven RCTs; 5438 patients; FEM; OR = 0.57; 95% CI 0.23, 1.43), adverse events (five RCTs; 3214 patients; FEM; OR = 0. 90; 95% CI 0.72, 1.13) or withdrawals as a result of adverse events. No differences were found in subset analyses of adults or children, and of patients treated with no more than 5-day short-course regimens versus at least 7-day long-course regimens.
CONCLUSION: No difference was found in the effectiveness and safety of short- versus long-course antimicrobial treatment of adult and paediatric patients with CAP of mild to moderate severity.

PMID 18729535  Drugs. 2008;68(13):1841-54.
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: Catherine Liu, Arnold Bayer, Sara E Cosgrove, Robert S Daum, Scott K Fridkin, Rachel J Gorwitz, Sheldon L Kaplan, Adolf W Karchmer, Donald P Levine, Barbara E Murray, Michael J Rybak, David A Talan, Henry F Chambers, 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/・・・

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