厚生労働省. 薬剤耐性（AMR）対策について｜厚生労働省 [Internet]. [cited 2019 Jul 11]. Available from: https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000120172.html
David N Juurlink, Muhammad Mamdani, Alexander Kopp, Andreas Laupacis, Donald A Redelmeier
Drug-drug interactions among elderly patients hospitalized for drug toxicity.
JAMA. 2003 Apr 2;289(13):1652-8. doi: 10.1001/jama.289.13.1652.
Abstract/Text
CONTEXT: Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized.
OBJECTIVE: To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission.
DESIGN: Three population-based, nested case-control studies.
SETTING: Ontario, Canada, from January 1, 1994, to December 31, 2000.
PATIENTS: All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors).
MAIN OUTCOME MEASURE: Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date.
RESULTS: During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively).
CONCLUSIONS: Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.
J Michael Miller, Matthew J Binnicker, Sheldon Campbell, Karen C Carroll, Kimberle C Chapin, Peter H Gilligan, Mark D Gonzalez, Robert C Jerris, Sue C Kehl, Robin Patel, Bobbi S Pritt, Sandra S Richter, Barbara Robinson-Dunn, Joseph D Schwartzman, James W Snyder, Sam Telford, Elitza S Theel, Richard B Thomson, Melvin P Weinstein, Joseph D Yao
A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.
Clin Infect Dis. 2018 Aug 31;67(6):813-816. doi: 10.1093/cid/ciy584.
Abstract/Text
The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.
Andrew Lee, Stanley Mirrett, L Barth Reller, Melvin P Weinstein
Detection of bloodstream infections in adults: how many blood cultures are needed?
J Clin Microbiol. 2007 Nov;45(11):3546-8. doi: 10.1128/JCM.01555-07. Epub 2007 Sep 19.
Abstract/Text
Although several reports have shown that two to three 20-ml blood cultures are adequate for the detection of bacteremia and fungemia in adults, a recent study (F. R. Cockerill et al., Clin. Infect. Dis. 38:1724-1730, 2004) found that two blood cultures detected only 80% of bloodstream infections and that three blood cultures detected 96% of episodes. We reviewed data at two university hospitals to determine whether the recent observations by Cockerill et al. are applicable more widely. We assessed all blood cultures obtained from adult inpatients from 1 January 2004 through 31 December 2005 at Robert Wood Johnson University Hospital and Duke University Medical Center. All instances in which > or =3 blood cultures per patient were obtained during a 24-h period were included. The medical records of patients who met the inclusion criteria were reviewed retrospectively to determine the clinical significance of the positive blood culture (true infection versus contamination). Data were analyzed to determine the cumulative sensitivity of blood cultures obtained sequentially during the 24-h time period. Of 629 unimicrobial episodes with > or =3 blood cultures obtained during the 24-h period, 460 (73.1%) were detected with the first blood culture, 564 (89.7%) were detected with the first two blood cultures, 618 (98.2%) were detected with the first three blood cultures, and 628 (99.8%) were detected with the first four blood cultures. Of 351 unimicrobial episodes with > or =4 blood cultures obtained during the 24-h period, 257 (73.2%) were detected with the first blood culture, 308 (93.9%) were detected with the first two blood cultures, 340 (96.9%) were detected with the first three blood cultures, and 350 (99.7%) were detected with the first four blood cultures. Among unimicrobial episodes, Staphylococcus aureus was more likely to be detected with the first blood culture (approximately 90% detected with the first blood culture). There were 58 polymicrobial episodes in which > or =3 blood cultures were obtained. Forty-seven (81.0%) were detected with the first blood culture, 54 (93.1%) were detected with the first two blood cultures, and 58 (100%) were detected with the first three blood cultures. The results of this study indicate that two blood cultures in a 24-h period will detect approximately 90% of bloodstream infections in adults. To achieve a detection rate of >99%, as many as four blood cultures may be needed. The previously held axiom that virtually all bloodstream infections can be detected with two to three blood cultures may no longer be valid but may also depend on the definition of the "first" blood culture obtained (see Materials and Methods and Discussion in the text).
R W Geckler, D H Gremillion, C K McAllister, C Ellenbogen
Microscopic and bacteriological comparison of paired sputa and transtracheal aspirates.
J Clin Microbiol. 1977 Oct;6(4):396-9.
Abstract/Text
Ninety-six sputum specimens from patiens with pneumonia were microscopically screened for leukocytes and buccal squamous epithelial (BSE) cells. Cultures of these specimens were compared with cultures of paired transtracheal aspirates (TTA). Agreement between sputa with less than 25 BSE cells per 100X field and TTA was good (79%). Only 27% of the specimens with greater than 25 BSE cells per 100X field agreed with TTA. Sixty-six of the sputa were of group 5 quality, i.e., greater than 25 leukocytes and less than 10 BSE cells per 100X field. A potential pathogen growing in one of these specimens was 94% predictive of growth in the TTA. If a group 5 sputum was negative for a potential pathogen, there was a 45% chance that a fastidious organism had been overgrown or overlooked. The presence of definite lower tract secretions in group 5 sputa as determined by visualizing bronchial epithelial cells and alveolar macrophages did not significantly increase the diagnostic value of these specimens. Microscopic screening of sputum before culture with rejection of selected specimens can increase the value of sputum in determining the etiology of bacterial pneumonia.
Thomas M Hooton, Suzanne F Bradley, Diana D Cardenas, Richard Colgan, Suzanne E Geerlings, James C Rice, Sanjay Saint, Anthony J Schaeffer, Paul A Tambayh, Peter Tenke, Lindsay E Nicolle, Infectious Diseases Society of America
Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America.
Clin Infect Dis. 2010 Mar 1;50(5):625-63.
Abstract/Text
Guidelines for the diagnosis, prevention, and management of persons with catheter-associated urinary tract infection (CA-UTI), both symptomatic and asymptomatic, were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic criteria, strategies to reduce the risk of CA-UTIs, strategies that have not been found to reduce the incidence of urinary infections, and management strategies for patients with catheter-associated asymptomatic bacteriuria or symptomatic urinary tract infection. These guidelines are intended for use by physicians in all medical specialties who perform direct patient care, with an emphasis on the care of patients in hospitals and long-term care facilities.
Sarah M Menzies, Najib M Rahman, John M Wrightson, Helen E Davies, Robert Shorten, Stephen H Gillespie, Christopher W H Davies, Nick A Maskell, Andrew A Jeffrey, Y C Gary Lee, Robert J O Davies
Blood culture bottle culture of pleural fluid in pleural infection.
Thorax. 2011 Aug;66(8):658-62. doi: 10.1136/thx.2010.157842. Epub 2011 Apr 1.
Abstract/Text
BACKGROUND: Pleural infection is common, and has a >30% major morbidity and mortality-particularly when infection is caused by Gram-negative, Staphylococcus aureus or mixed aerobic pathogens. Standard pleural fluid culture is negative in ∼40% of cases. Culturing pleural fluid in blood culture bottles may increase microbial yield, and is cheap and easy to perform.
OBJECTIVES: To determine whether inoculating pleural fluid into blood culture bottles increases the culture positivity of pleural infection over standard laboratory culture, and to assess the optimum volume of inoculum to introduce.
METHODS: 62 patients with pleural infection were enrolled. Pairs of aerobic and anaerobic blood culture bottles were inoculated at the bedside with 2, 5 or 10 ml of pleural fluid, and two pleural fluid specimens were sent for standard culture. Pleural fluid from nine control patients was cultured to test for 'false-positive' results.
RESULTS: The addition of blood culture bottle culture to standard culture increased the proportion of patients with identifiable pathogens by 20.8% (20/53 (37.7%) to 31/53 (58.5%) (difference 20.8%, 95% CI difference 8.9% to 20.8%, p<0.001)). The second standard culture did not similarly improve the culture positivity (19/49 (38.8%) to 22/49 (44.9%) (difference 6.1%, 95% CI difference -2.5% to 6.1%, p=0.08)). The culture inoculum volume did not influence bacterial isolation frequency. The control fluids were culture negative.
CONCLUSIONS: Blood culture bottle culture of infected pleural fluid increases microbial yield when used in addition to standard culture. This technique should be part of routine care.
M J Mulligan, C G Cobbs
Bacteriostatic versus bactericidal activity.
Infect Dis Clin North Am. 1989 Sep;3(3):389-98.
Abstract/Text
Antibiotics alone or in combination may either inhibit or kill bacteria. Laboratory methods are available to determine the activity of various antimicrobial agents and can aid the physician in selecting appropriate antimicrobial therapy for specific infectious disease disorders. A few infectious processes appear to require bactericidal antimicrobial therapy for cure. Additional multicenter trials of the ability of a standardized SBT to predict therapeutic outcome in specific bacterial diseases are required.
Marilyn N Martinez, Mark G Papich, George L Drusano
Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target.
Antimicrob Agents Chemother. 2012 Jun;56(6):2795-805. doi: 10.1128/AAC.05360-11. Epub 2012 Feb 27.
Abstract/Text
To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent suboptimal systemic drug concentrations prior to the attainment of a steady state. Suboptimal (inadequate) exposure can produce amplification of resistant bacteria. This minireview provides an overview of published evidence supporting the positions that, in most situations, it is the exposure achieved during the first dose that is relevant for determining the therapeutic outcome of an infection, therapeutic intervention should be initiated as soon as possible to minimize the size of the bacterial burden at the infection site, and the duration of drug administration should be kept as brief as clinically appropriate to reduce the risk of selecting for resistant (or phenotypically nonresponsive) microbial strains. To support these recommendations, we briefly discuss data on inoculum effects, persister cells, and the concept of time within some defined mutation selection window.
Jared A Silverman, Lawrence I Mortin, Andrew D G Vanpraagh, Tongchuan Li, Jeff Alder
Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact.
J Infect Dis. 2005 Jun 15;191(12):2149-52. doi: 10.1086/430352. Epub 2005 May 5.
Abstract/Text
The lipopeptide daptomycin has been approved for use in skin and skin-structure infections but has failed to meet statistical noninferiority criteria in a clinical trial for severe community-acquired pneumonia. Daptomycin exhibited an unusual pattern of activity in pulmonary animal models: efficacy in Staphylococcus aureus hematogenous pneumonia and inhalation anthrax but no activity against Streptococcus pneumoniae in simple bronchial-alveolar pneumonia. Daptomycin was shown to interact in vitro with pulmonary surfactant, resulting in inhibition of antibacterial activity. This effect was specific to daptomycin and consistent with its known mechanism of action. This represents the first example of organ-specific inhibition of an antibiotic.
日本化学療法学会、日本TDM 学会：抗菌薬 TDM 臨床実践ガイドライン 2022、日本化学療法学会雑誌 Vol. 70, 2022年1号（1月） p.1～72.
Dominik Mertz, Michael Koller, Patricia Haller, Markus L Lampert, Herbert Plagge, Balthasar Hug, Gian Koch, Manuel Battegay, Ursula Flückiger, Stefano Bassetti
Outcomes of early switching from intravenous to oral antibiotics on medical wards.
J Antimicrob Chemother. 2009 Jul;64(1):188-99. doi: 10.1093/jac/dkp131. Epub 2009 Apr 28.
Abstract/Text
OBJECTIVES: To evaluate outcomes following implementation of a checklist with criteria for switching from intravenous (iv) to oral antibiotics on unselected patients on two general medical wards.
METHODS: During a 12 month intervention study, a printed checklist of criteria for switching on the third day of iv treatment was placed in the medical charts. The decision to switch was left to the discretion of the attending physician. Outcome parameters of a 4 month control phase before intervention were compared with the equivalent 4 month period during the intervention phase to control for seasonal confounding (before-after study; April to July of 2006 and 2007, respectively): 250 episodes (215 patients) during the intervention period were compared with the control group of 176 episodes (162 patients). The main outcome measure was the duration of iv therapy. Additionally, safety, adherence to the checklist, reasons against switching patients and antibiotic cost were analysed during the whole year of the intervention (n = 698 episodes).
RESULTS: In 38% (246/646) of episodes of continued iv antibiotic therapy, patients met all criteria for switching to oral antibiotics on the third day, and 151/246 (61.4%) were switched. The number of days of iv antibiotic treatment were reduced by 19% (95% confidence interval 9%-29%, P = 0.001; 6.0-5.0 days in median) with no increase in complications. The main reasons against switching were persisting fever (41%, n = 187) and absence of clinical improvement (41%, n = 185).
CONCLUSIONS: On general medical wards, a checklist with bedside criteria for switching to oral antibiotics can shorten the duration of iv therapy without any negative effect on treatment outcome. The criteria were successfully applied to all patients on the wards, independently of the indication (empirical or directed treatment), the type of (presumed) infection, the underlying disease or the group of antibiotics being used.
F Sevinç, J M Prins, R P Koopmans, P N Langendijk, P M Bossuyt, J Dankert, P Speelman
Early switch from intravenous to oral antibiotics: guidelines and implementation in a large teaching hospital.
J Antimicrob Chemother. 1999 Apr;43(4):601-6. doi: 10.1093/jac/43.4.601.
Abstract/Text
In recent years 'switch therapy' has been advocated: short intravenous antibiotic therapy, for 2-3 days, followed by oral treatment for the remainder of the course. Little is known about the number of patients that could benefit from early switch therapy and the consequences of introducing this strategy in everyday practice. We prospectively registered all antibiotic courses on wards for Internal Medicine, Surgery, and Pulmonology during a 2 month period, before (n = 362, inventorial phase) and after (n = 281, implementation phase) the introduction of guidelines for switching therapy. Approximately 40% of all patients who started on iv antibiotics were candidates for an early iv-oral switch. During the inventorial phase, 54% (52/97) of eligible patients were switched to oral treatment, after a median of 6 days (range 2-28 days). After implementation of the guidelines, this percentage rose to 83% (66/80) (difference 29%, 95% CI 16-42%; P < 0.001). Therapy was also switched earlier, after a median of 4 days (range 2 to 16 days). In the 6 weeks after completion of the oral course, recurrence of infections, or readmissions due to reinfections did not occur. Compared with the inventorial phase, 43% of iv administrations could be avoided, that is >6000 per year. This means a potential annual reduction of dfl.60,000 (c. US$30,000) of administration costs. The potential savings in purchase costs of the antibiotics were dfl.54,000 (US$27,000) annually. In conclusion, a substantial number of patients starting on iv antibiotics were candidates for an early iv-oral switch. The guidelines were well accepted by the physicians and substantial savings in costs and nursing time were achieved.
Zhi-Kang Ye, Hui-Lin Tang, Suo-Di Zhai
Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis.
PLoS One. 2013;8(10):e77169. doi: 10.1371/journal.pone.0077169. Epub 2013 Oct 18.
Abstract/Text
BACKGROUND AND OBJECTIVE: The necessity of therapeutic drug monitoring (TDM) for vancomycin is controversial. The objective of the current review was to evaluate the available evidence for the necessity of TDM in patients given vancomycin to treat Gram-positive infections.
METHODS: Medline, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were searched. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM groups vs. non-TDM groups were included. Two reviewers independently extracted the data. The primary outcome was clinical efficacy of therapy. Secondary outcomes included vancomycin associated nephrotoxicity, duration of vancomycin therapy, length of hospital stay, and mortality. Meta-analysis was performed using the Mantel-Haenszel fixed effect method (FEM). Odds ratios (ORs) or weighted mean differences (WMD) with 95% confidence intervals (95%CIs) were calculated for categorical and continuous outcomes, respectively.
RESULTS: One randomized controlled trial (RCT) and five cohort studies were included in the meta-analysis. Compared with non-TDM groups, TDM groups had significantly higher rates of clinical efficacy (OR = 2.62, 95%CI 1.34-5.11 P = 0.005) and decreased rates of nephrotoxicity (OR = 0.25, 95%CI 0.13-0.48 P<0.0001). Subgroup analyses showed that TDM group had significantly higher rates of clinical efficacy in both cohort studies subgroup (OR = 3.04, 95%CI 1.34-6.90) and in Asian population subgroup (OR = 3.04, 95%CI 1.34-6.90). TDM group had significantly decreased rates of nephrotoxicity in all subgroup. There was no significant difference in duration of vancomycin therapy (WMD = -0.40, 95%CI -2.83-2.02 P = 0.74) or length of stay (WMD = -1.01, 95%CI -7.51-5.49 P = 0.76) between TDM and non-TDM groups. Subgroup analyses showed there were no differences in duration of vancomycin therapy. Only one study reported mortality rates.
CONCLUSIONS: Studies to date show that TDM significantly increases the rate of clinical efficacy and decreases the rate of nephrotoxicity in patients treated with vancomycin.
Michael J Rybak, Jennifer Le, Thomas P Lodise, Donald P Levine, John S Bradley, Catherine Liu, Bruce A Mueller, Manjunath P Pai, Annie Wong-Beringer, John C Rotschafer, Keith A Rodvold, Holly D Maples, Benjamin M Lomaestro
Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.
Am J Health Syst Pharm. 2020 May 19;77(11):835-864. doi: 10.1093/ajhp/zxaa036.
Abstract/Text
Anand Kumar, Daniel Roberts, Kenneth E Wood, Bruce Light, Joseph E Parrillo, Satendra Sharma, Robert Suppes, Daniel Feinstein, Sergio Zanotti, Leo Taiberg, David Gurka, Aseem Kumar, Mary Cheang
Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.
Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
Abstract/Text
OBJECTIVE: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock.
DESIGN: A retrospective cohort study performed between July 1989 and June 2004.
SETTING: Fourteen intensive care units (four medical, four surgical, six mixed medical/surgical) and ten hospitals (four academic, six community) in Canada and the United States.
PATIENTS: Medical records of 2,731 adult patients with septic shock.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103-1.136, p<.0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypotension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25-75th percentile, 2.0-15.0 hrs).
CONCLUSIONS: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension.
Mitchell M Levy, Laura E Evans, Andrew Rhodes
The Surviving Sepsis Campaign Bundle: 2018 update.
Intensive Care Med. 2018 Jun;44(6):925-928. doi: 10.1007/s00134-018-5085-0. Epub 2018 Apr 19.
Abstract/Text
Kelly E Dooley, Jonathan Golub, Fernando S Goes, William G Merz, Timothy R Sterling
Empiric treatment of community-acquired pneumonia with fluoroquinolones, and delays in the treatment of tuberculosis.
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.
Lionel A Mandell, Richard G Wunderink, Antonio Anzueto, John G Bartlett, G Douglas Campbell, Nathan C Dean, Scott F Dowell, Thomas M File, Daniel M Musher, Michael S Niederman, Antonio Torres, Cynthia G Whitney, Infectious Diseases Society of America, American Thoracic Society
Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72. doi: 10.1086/511159.
Abstract/Text
Kalpana Gupta, Thomas M Hooton, Kurt G Naber, Björn Wullt, Richard Colgan, Loren G Miller, Gregory J Moran, Lindsay E Nicolle, Raul Raz, Anthony J Schaeffer, David E Soper, Infectious Diseases Society of America, European Society for Microbiology and Infectious Diseases
International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.
Clin Infect Dis. 2011 Mar 1;52(5):e103-20. doi: 10.1093/cid/ciq257.
Abstract/Text
A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.
Dafna Yahav, Erica Franceschini, Fidi Koppel, Adi Turjeman, Tanya Babich, Roni Bitterman, Ami Neuberger, Nesrin Ghanem-Zoubi, Antonella Santoro, Noa Eliakim-Raz, Barak Pertzov, Tali Steinmetz, Anat Stern, Yaakov Dickstein, Elias Maroun, Hiba Zayyad, Jihad Bishara, Danny Alon, Yonatan Edel, Elad Goldberg, Claudia Venturelli, Cristina Mussini, Leonard Leibovici, Mical Paul, Bacteremia Duration Study Group
Seven versus fourteen Days of Antibiotic Therapy for uncomplicated Gram-negative Bacteremia: a Non-inferiority Randomized Controlled Trial.
Clin Infect Dis. 2018 Dec 11;. doi: 10.1093/cid/ciy1054. Epub 2018 Dec 11.
Abstract/Text
Background: Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.
Methods: Randomized, multicenter, open-label, non-inferiority trial. Inpatients with Gram-negative bacteremia, afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative or distant complications; and re-admission or extended hospitalization (>14 days). The non-inferiority margin was set at 10%.
Results: We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in three centers in Israel and Italy. The source of the infection was urinary in 411/604 (68%); causative pathogens were mainly Enterobacteriaceae (543/604, 90%). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140/306 (45.8%) patients in the 7 days group versus 144/298 (48.3%) in the 14 days group (risk difference [RD] -2.6%, 95% confidence interval [CI] -10.5% to 5.3%). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short therapy arm.
Conclusions: In patients hospitalized with Gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was non-inferior to 14 days. Reducing antibiotic treatment for uncomplicated Gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. (ClinicalTrials.gov number, NCT01737320).
Darunee Chotiprasitsakul, Jennifer H Han, Sara E Cosgrove, Anthony D Harris, Ebbing Lautenbach, Anna T Conley, Pam Tolomeo, Jacqueleen Wise, Pranita D Tamma, Antibacterial Resistance Leadership Group
Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score-Matched Cohort.
Clin Infect Dis. 2018 Jan 6;66(2):172-177. doi: 10.1093/cid/cix767.
Abstract/Text
Background: The recommended duration of antibiotic treatment for Enterobacteriaceae bloodstream infections is 7-14 days. We compared the outcomes of patients receiving short-course (6-10 days) vs prolonged-course (11-16 days) antibiotic therapy for Enterobacteriaceae bacteremia.
Methods: A retrospective cohort study was conducted at 3 medical centers and included patients with monomicrobial Enterobacteriaceae bacteremia treated with in vitro active therapy in the range of 6-16 days between 2008 and 2014. 1:1 nearest neighbor propensity score matching without replacement was performed prior to regression analysis to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment comparing patients in the 2 treatment groups. Secondary outcomes included recurrent bloodstream infections, Clostridium difficile infections (CDI), and the emergence of multidrug-resistant gram-negative (MDRGN) bacteria, all within 30 days after the end of antibiotic therapy.
Results: There were 385 well-balanced matched pairs. The median duration of therapy in the short-course group and prolonged-course group was 8 days (interquartile range [IQR], 7-9 days) and 15 days (IQR, 13-15 days), respectively. No difference in mortality between the treatment groups was observed (adjusted hazard ratio [aHR], 1.00; 95% confidence interval [CI], .62-1.63). The odds of recurrent bloodstream infections and CDI were also similar. There was a trend toward a protective effect of short-course antibiotic therapy on the emergence of MDRGN bacteria (odds ratio, 0.59; 95% CI, .32-1.09; P = .09).
Conclusions: Short courses of antibiotic therapy yield similar clinical outcomes as prolonged courses of antibiotic therapy for Enterobacteriaceae bacteremia, and may protect against subsequent MDRGN bacteria.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Harumi Gomi, Joseph S Solomkin, David Schlossberg, Kohji Okamoto, Tadahiro Takada, Steven M Strasberg, Tomohiko Ukai, Itaru Endo, Yukio Iwashita, Taizo Hibi, Henry A Pitt, Naohisa Matsunaga, Yoriyuki Takamori, Akiko Umezawa, Koji Asai, Kenji Suzuki, Ho-Seong Han, Tsann-Long Hwang, Yasuhisa Mori, Yoo-Seok Yoon, Wayne Shih-Wei Huang, Giulio Belli, Christos Dervenis, Masamichi Yokoe, Seiki Kiriyama, Takao Itoi, Palepu Jagannath, O James Garden, Fumihiko Miura, Eduardo de Santibañes, Satoru Shikata, Yoshinori Noguchi, Keita Wada, Goro Honda, Avinash Nivritti Supe, Masahiro Yoshida, Toshihiko Mayumi, Dirk J Gouma, Daniel J Deziel, Kui-Hin Liau, Miin-Fu Chen, Keng-Hao Liu, Cheng-Hsi Su, Angus C W Chan, Dong-Sup Yoon, In-Seok Choi, Eduard Jonas, Xiao-Ping Chen, Sheung Tat Fan, Chen-Guo Ker, Mariano Eduardo Giménez, Seigo Kitano, Masafumi Inomata, Shuntaro Mukai, Ryota Higuchi, Koichi Hirata, Kazuo Inui, Yoshinobu Sumiyama, Masakazu Yamamoto
Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis.
J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):3-16. doi: 10.1002/jhbp.518. Epub 2018 Jan 9.
Abstract/Text
Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community-acquired and healthcare-associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class-definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de-escalation or termination of antimicrobial therapy are now important parts of decision-making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
E Forsblom, E Ruotsalainen, J Ollgren, A Järvinen
Telephone consultation cannot replace bedside infectious disease consultation in the management of Staphylococcus aureus Bacteremia.
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.
V G Fowler, L L Sanders, D J Sexton, L Kong, K A Marr, A K Gopal, G Gottlieb, R S McClelland, G R Corey
Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients.
Clin Infect Dis. 1998 Sep;27(3):478-86.
Abstract/Text
To determine whether recommendations of infectious diseases specialists affect outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus aureus bacteremia. We offered our management recommendations to each patient's physicians and then assessed the clinical outcome for both patients for whom our consultative advice was followed and those for whom our advice was not heeded. All patients were followed up for 12 weeks after their first positive blood culture. Our management advice was followed for 112 patients (45.9%) and partially or completely ignored for 132 patients (54.1%). Patients for whom our recommendations were followed were more likely to be cured of their S. aureus infection and less likely to relapse (P < .01), despite having significantly more metastatic infections (P < .01) at the outset of therapy, than were those for whom our recommendations were not followed. Failure to follow recommendations to remove an infected intravascular device was the most important risk for treatment failure. After controlling for other factors, logistic regression analysis revealed that patients whose intravascular device was not removed were 6.5 times more likely to relapse or die of their infection than were those whose device was removed. Our findings suggest that patient-specific management advice by infectious diseases consultants can improve the clinical outcome for patients with S. aureus bacteremia.
E J MacLaughlin, J J Saseen, D C Malone
Costs of beta-lactam allergies: selection and costs of antibiotics for patients with a reported beta-lactam allergy.
Arch Fam Med. 2000 Aug;9(8):722-6.
Abstract/Text
OBJECTIVE: To evaluate antibiotic selection and the cost effect of reported beta-lactam allergies.
DESIGN: Retrospective medical records review comparing antimicrobial selection and costs in patients with a reported beta-lactam allergy with a group in which no such allergy had been documented.
SETTING: University-based family medicine clinic.
PATIENTS: Patients who were prescribed at least 1 antibiotic for an upper respiratory tract infection, otitis media, sinusitis, and/or a urinary tract infection were eligible. One thousand two hundred one patients were identified via ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes. Four hundred sixty-five patients were initially identified and an additional 195 family members were eligible for inclusion.
MAIN OUTCOME MEASURES: Comparison of antimicrobial selection and costs (by average wholesale price) between patients with and without a reported beta-lactam allergy.
RESULTS: Of the 660 patients eligible for inclusion, 99 (15%) had a documented beta-lactam allergy. Of the patients with a documented allergy, only 33% had a description of their purported reaction. The mean antibiotic cost for patients with a beta-lactam allergy was significantly higher compared with those without a beta-lactam allergy ($26.81 vs $16.28, respectively; P =.004). Patients with a beta-lactam allergy were more likely to have received a cephalosporin, macrolide, or a miscellaneous agent (eg, quinolone, tetracycline, or nitrofurantoin) (P =.001).
CONCLUSIONS: Patients with a beta-lactam allergy had higher antibiotic costs and were more likely to receive a broader-spectrum antibiotic. Most patients with a reported allergy did not have a description of their reaction. Skin testing may be of use in detecting true beta-lactam allergies; however, further study is needed to determine its cost-effectiveness.
N Yawalkar, W J Pichler
Immunohistology of drug-induced exanthema: clues to pathogenesis.
Curr Opin Allergy Clin Immunol. 2001 Aug;1(4):299-303.
Abstract/Text
Hypersensitivity reactions to drugs can cause a variety of different skin disorders, the most frequent being maculopapular eruptions. In recent years increasing evidence has indicated the important involvement of T cells in this drug reaction. Histopathological changes typically show a dominant T-cell infiltration together with vacuolar interface dermatitis. Immunohistochemical studies demonstrate the presence of cytotoxic CD4+ and CD8+ T cells, which contain perforin and granzyme B, in close proximity to keratinocytes showing signs of cell destruction. Expression of Fas ligand is barely detectable, which suggests that cytotoxic granule exocytosis may be the dominant pathway leading to keratinocyte cell damage. In addition, drug-specific T cells may orchestrate the inflammatory skin reaction through the release and induction of various cytokines (i.e. IL-5, IL-6, TNF-alpha, IFN-gamma) and chemokines (i.e. regulated on activation, normal T-cell expressed and secreted; eotaxin). These mediators contribute to the generation of eosinophilia, which may amplify the underlying immune response through the release of further proinflammatory mediators in drug-induced maculopapular exanthema.
A Romano, M Blanca, M J Torres, A Bircher, W Aberer, K Brockow, W J Pichler, P Demoly, ENDA, EAACI
Diagnosis of nonimmediate reactions to beta-lactam antibiotics.
Allergy. 2004 Nov;59(11):1153-60. doi: 10.1111/j.1398-9995.2004.00678.x.
Abstract/Text
Nonimmediate manifestations (i.e. occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common during beta-lactam treatment. The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood. However, clinical and immunohistological studies, as well as analysis of drug-specific T-cell clones obtained from the circulating blood and the skin, suggest that a type-IV (cell-mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis. In the diagnostic work-up, the patient's history is fundamental; patch testing is useful, together with delayed-reading intradermal testing. The latter appears to be somewhat more sensitive than patch testing, but also less specific. In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents. With regard to in vitro tests, the lymphocyte transformation test may contribute to the identification of the responsible drug. Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions to beta-lactams.
Copyright 2004 Blackwell Munksgaard
Pranita D Tamma, Samuel L Aitken, Robert A Bonomo, Amy J Mathers, David van Duin, Cornelius J Clancy
Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections.
Clin Infect Dis. 2023 Jul 18;. doi: 10.1093/cid/ciad428. Epub 2023 Jul 18.
Abstract/Text
BACKGROUND: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document.
METHODS: A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR-P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States.
RESULTS: Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are also discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults.
CONCLUSIONS: The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial resistant infections. This document is current as of December 31, 2022 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Mical Paul, Elena Carrara, Pilar Retamar, Thomas Tängdén, Roni Bitterman, Robert A Bonomo, Jan de Waele, George L Daikos, Murat Akova, Stephan Harbarth, Celine Pulcini, José Garnacho-Montero, Katja Seme, Mario Tumbarello, Paul Christoffer Lindemann, Sumanth Gandra, Yunsong Yu, Matteo Bassetti, Johan W Mouton, Evelina Tacconelli, Jesús Rodríguez-Baño
European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine).
Clin Microbiol Infect. 2022 Apr;28(4):521-547. doi: 10.1016/j.cmi.2021.11.025. Epub 2021 Dec 16.
Abstract/Text
SCOPE: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy.
METHODS: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak).
RECOMMENDATIONS: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Patrick N A Harris, Paul A Tambyah, David C Lye, Yin Mo, Tau H Lee, Mesut Yilmaz, Thamer H Alenazi, Yaseen Arabi, Marco Falcone, Matteo Bassetti, Elda Righi, Benjamin A Rogers, Souha Kanj, Hasan Bhally, Jon Iredell, Marc Mendelson, Tom H Boyles, David Looke, Spiros Miyakis, Genevieve Walls, Mohammed Al Khamis, Ahmed Zikri, Amy Crowe, Paul Ingram, Nick Daneman, Paul Griffin, Eugene Athan, Penelope Lorenc, Peter Baker, Leah Roberts, Scott A Beatson, Anton Y Peleg, Tiffany Harris-Brown, David L Paterson, MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN)
Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial.
JAMA. 2018 Sep 11;320(10):984-994. doi: 10.1001/jama.2018.12163.
Abstract/Text
Importance: Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.
Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.
Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.
Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.
Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.
Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.
Conclusions and relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.
Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.
Asako Doi, Toshihiko Shimada, Sohei Harada, Kentaro Iwata, Toru Kamiya
The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.
Int J Infect Dis. 2013 Mar;17(3):e159-63. doi: 10.1016/j.ijid.2012.09.010. Epub 2012 Nov 8.
Abstract/Text
OBJECTIVES: Urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are on the increase. Although cefmetazole is stable in vitro against the hydrolyzing activity of ESBLs, no clinical study has ever evaluated its role in infections caused by these organisms. We therefore evaluated the efficacy of cefmetazole compared to carbapenems against pyelonephritis caused by ESBL-producing Enterobacteriaceae.
METHODS: A retrospective chart review was conducted at a tertiary care hospital from August 2008 to July 2010. Chart reviews were done for patients with ESBL-producing organisms in urine identified in the microbiology database. Patients who were treated with cefmetazole were compared to those treated with carbapenems. The clinical and bacteriological cure rates at 4 weeks after completion of therapy were evaluated.
RESULTS: Two hundred and fifty-six urine cultures growing ESBL-producing organisms were identified during the study period. Ten patients treated with cefmetazole and 12 patients treated with carbapenems were evaluated. There was no difference in clinical (9/10 vs. 12/12, p = 0.46) or bacteriological cure rate (5/7 vs. 6/7, p = 1.00) at 4 weeks after the completion of therapy. There was no difference in the incidence of adverse effects (2/10 vs. 2/12, p = 1.00).
CONCLUSIONS: Cefmetazole may be a useful option for the treatment of UTIs caused by ESBL-producing organisms. Prospective and larger sized studies are needed to confirm our findings.
Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
J W Chow, M J Fine, D M Shlaes, J P Quinn, D C Hooper, M P Johnson, R Ramphal, M M Wagener, D K Miyashiro, V L Yu
Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy.
Ann Intern Med. 1991 Oct 15;115(8):585-90.
Abstract/Text
OBJECTIVES: To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia.
DESIGN: Prospective, observational study of consecutive patients with Enterobacter bacteremia.
SETTING: Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers.
PATIENTS: A total of 129 adult patients were studied.
MEASUREMENTS: The two main end points were emergence of resistance during antibiotic therapy and death.
MAIN RESULTS: Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy.
CONCLUSIONS: More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.
Pranita D Tamma, Sonya C T Girdwood, Ravindra Gopaul, Tsigereda Tekle, Ava A Roberts, Anthony D Harris, Sara E Cosgrove, Karen C Carroll
The use of cefepime for treating AmpC β-lactamase-producing Enterobacteriaceae.
Clin Infect Dis. 2013 Sep;57(6):781-8. doi: 10.1093/cid/cit395. Epub 2013 Jun 11.
Abstract/Text
BACKGROUND: AmpC β-lactamase-producing organisms are associated with significant morbidity and mortality. Induction of resistance to third-generation cephalosporins after exposure to these agents complicates treatment options and carbapenems are considered optimal therapy. The role of cefepime, however, remains unclear. Our objective was to compare clinical outcomes for patients receiving cefepime compared with meropenem for invasive infections caused by organisms expressing AmpC β-lactamases.
METHODS: Hospitalized patients with blood, bronchoalveolar lavage, or intra-abdominal fluid cultures growing Enterobacter spp, Serratia spp, or Citrobacter spp were evaluated using the cefotetan-boronic acid disk test and the cefotetan-cloxacillin Etest to identify organisms with AmpC β-lactamase production from February 2010 to January 2011. In patients with organisms hyperproducing AmpC β-lactamases (positive by both methods), clinical outcomes for patients receiving cefepime or meropenem therapy were compared. To minimize the possibility of treatment selection bias, 1:1 nearest neighbor propensity score matching was performed prior to regression analysis.
RESULTS: Of 399 patients meeting eligibility criteria, 96 (24%) had confirmed infections with AmpC β-lactamase-producing organisms. Propensity score matching of patients infected with AmpC β-lactamase-positive organisms treated with cefepime or meropenem yielded 32 well-balanced patient pairs with no difference in 30-day mortality (odds ratio, 0.63; 95% confidence interval [CI], .23-2.11; P = .36) or length of hospital stay after infection (relative risk, 0.96; 95% CI, .79-1.26; P = .56) between the 2 groups.
CONCLUSIONS: Cefepime may be a reasonable option for the treatment of invasive infections due to AmpC β-lactamase-producing organisms, particularly when adequate source control is achieved.
E A Halm, M J Fine, T J Marrie, C M Coley, W N Kapoor, D S Obrosky, D E Singer
Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines.
JAMA. 1998 May 13;279(18):1452-7. doi: 10.1001/jama.279.18.1452.
Abstract/Text
CONTEXT: Many groups have developed guidelines to shorten hospital length of stay in pneumonia in order to decrease costs, but the length of time until a patient hospitalized with pneumonia becomes clinically stable has not been established.
OBJECTIVE: To describe the time to resolution of abnormalities in vital signs, ability to eat, and mental status in patients with community-acquired pneumonia and assess clinical outcomes after achieving stability.
DESIGN: Prospective, multicenter, observational cohort study.
SETTING: Three university and 1 community teaching hospital in Boston, Mass, Pittsburgh, Pa, and Halifax, Nova Scotia.
PATIENTS: Six hundred eighty-six adults hospitalized with community-acquired pneumonia.
MAIN OUTCOME MEASURES: Time to resolution of vital signs, ability to eat, mental status, hospital length of stay, and admission to an intensive care, coronary care, or telemetry unit.
RESULTS: The median time to stability was 2 days for heart rate (< or =100 beats/min) and systolic blood pressure (> or =90 mm Hg), and 3 days for respiratory rate (< or =24 breaths/min), oxygen saturation (> or =90%), and temperature (< or =37.2 degrees C [99 degrees F]). The median time to overall clinical stability was 3 days for the most lenient definition of stability and 7 days for the most conservative definition. Patients with more severe cases of pneumonia at presentation took longer to reach stability. Once stability was achieved, clinical deterioration requiring intensive care, coronary care, or telemetry monitoring occurred in 1% of cases or fewer. Between 65% to 86% of patients stayed in the hospital more than 1 day after reaching stability, and fewer than 29% to 46% were converted to oral antibiotics within 1 day of stability, depending on the definition of stability.
CONCLUSIONS: Our estimates of time to stability in pneumonia and explicit criteria for defining stability can provide an evidence-based estimate of optimal length of stay, and outline a clinically sensible approach to improving the efficiency of inpatient management.
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
Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.
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.
