Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Antibiotic Therapy for Sepsis
Top Cited Papers
- 1 November 2010
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 54 (11), 4851-4863
- https://doi.org/10.1128/aac.00627-10
Abstract
Quantifying the benefit of early antibiotic treatment is crucial for decision making and can be assessed only in observational studies. We performed a systematic review of prospective studies reporting the effect of appropriate empirical antibiotic treatment on all-cause mortality among adult inpatients with sepsis. Two reviewers independently extracted data. Risk of bias was assessed using the Newcastle-Ottawa score. We calculated unadjusted odds ratios (ORs) with 95% confidence intervals for each study and extracted adjusted ORs, with variance, methods, and covariates being used for adjustment. ORs were pooled using random-effects meta-analysis. We examined the effects of methodological and clinical confounders on results through subgroup analysis or mixed-effect meta-regression. Seventy studies were included, of which 48 provided an adjusted OR for inappropriate empirical antibiotic treatment. Inappropriate empirical antibiotic treatment was associated with significantly higher mortality in the unadjusted and adjusted comparisons, with considerable heterogeneity occurring in both analyses ( I 2 > 70%). Study design, time of mortality assessment, the reporting methods of the multivariable models, and the covariates used for adjustment were significantly associated with effect size. Septic shock was the only clinical variable significantly affecting results (it was associated with higher ORs). Studies adjusting for background conditions and sepsis severity reported a pooled adjusted OR of 1.60 (95% confidence interval = 1.37 to 1.86; 26 studies; number needed to treat to prevent one fatal outcome, 10 patients [95% confidence interval = 8 to 15]; I 2 = 46.3%) given 34% mortality with inappropriate empirical treatment. Appropriate empirical antibiotic treatment is associated with a significant reduction in all-cause mortality. However, the methods used in the observational studies significantly affect the effect size reported. Methods of observational studies assessing the effects of antibiotic treatment should be improved and standardized.Keywords
This publication has 109 references indexed in Scilit:
- Treatment with Fluoroquinolones or with β-Lactam-β-Lactamase Inhibitor Combinations Is a Risk Factor for Isolation of Extended-Spectrum-β-Lactamase-Producing Klebsiella Species in Hospitalized PatientsAntimicrobial Agents and Chemotherapy, 2010
- Controlling for Severity of Illness in Outcome Studies Involving Infectious Diseases: Impact of Measurement at Different Time PointsInfection Control & Hospital Epidemiology, 2008
- Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with Escherichia coli and Klebsiella pneumoniae Bacteremia: A Cohort StudyBMC Infectious Diseases, 2008
- Delay of Active Antimicrobial Therapy and Mortality among Patients with Bacteremia: Impact of Severe NeutropeniaAntimicrobial Agents and Chemotherapy, 2008
- Gram-negative bacteraemia in non-ICU patients: factors associated with inadequate antibiotic therapy and impact on outcomesJournal of Antimicrobial Chemotherapy, 2008
- Predictors of Carbapenem-Resistant Klebsiella pneumoniae Acquisition among Hospitalized Adults and Effect of Acquisition on MortalityAntimicrobial Agents and Chemotherapy, 2008
- Effect of antimicrobial therapy on mortality in 377 episodes of Enterobacter spp. bacteraemiaJournal of Antimicrobial Chemotherapy, 2008
- A Systematic Review of the Methods Used to Assess the Association between Appropriate Antibiotic Therapy and Mortality in Bacteremic PatientsClinical Infectious Diseases, 2007
- Impact of Empiric Antibiotic Therapy on Outcomes in Patients with Pseudomonas aeruginosa BacteremiaAntimicrobial Agents and Chemotherapy, 2007
- Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patientsBMJ, 2002