Outcome of Immediate Versus Early Antibiotics in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

Abstract

Study objective: Debate exists about the mortality benefit of administering antibiotics within either 1 or 3 hours of sepsis onset. We performed this meta-analysis to analyze the effect of immediate (0 to 1 hour after onset) versus early (1 to 3 hours after onset) antibiotics on mortality in patients with severe sepsis or septic shock.Methods: This review was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searched databases included PubMed, EMBASE, Web of Science, and Cochrane Library, as well as gray literature. Included studies were conducted with consecutive adults with severe sepsis or septic shock who received antibiotics within each period and provided mortality data. Data were extracted by 2 independent reviewers and pooled with random effects. Two authors independently assessed quality of evidence across all studies with Cochrane's Grading of Recommendations Assessment, Development and Evaluation methodology and risk of bias within each study, using the Newcastle-Ottawa Scale.Results: Thirteen studies were included: 5 prospective longitudinal and 8 retrospective cohort ones. Three studies (23%) had a high risk of bias (Newcastle-Ottawa Scale). Overall, quality of evidence across all studies (Grading of Recommendations Assessment, Development and Evaluation) was low. Pooling of data (33,863 subjects) showed no difference in mortality between patients receiving antibiotics in immediate versus early periods (odds ratio 1.09; 95% confidence interval 0.98 to 1.21). Analysis of severe sepsis studies (8,595 subjects) found higher mortality in immediate versus early periods (odds ratio 1.29; 95% confidence interval 1.09 to 1.53). Conclusion:We found no difference in mortality between immediate and early antibiotics across all patients. Although the quality of evidence across studies was low, these findings do not support a mortality benefit for immediate compared with early antibiotics across all patients with sepsis. [

Effectiveness of sepsis bundle application and outcomes predictors to cirrhotic patients with septic shock

“…Besides, the relatively lower baseline blood pressure in cirrhotic patients made the decision of early support of vasopressors for their hypotension more challenging [4]. In addition, the survival benefit of early administration of antimicrobial agents in septic shock patients has been questioned in several meta-analysis studies [28,29]. Taken together, little evidence exists to support that each component of the hour-1 bundle is equally effective and can be applied with equal consistency, especially in a physiologically unique and fragile cirrhosis group [27,30].…”

Impact of the timeliness of antibiotic therapy on the outcome of patients with sepsis and septic shock

“…51 Likewise, a metaregression analysis of 13 studies concluded that there was no difference in mortality between patients receiving antibiotics within one or three hours after the onset of sepsis. 52 In contrast, in a meta-analysis of 10 studies Johnston et al found a 33% reduction in the odds of mortality among patients in whom antibiotics were administred within one hour. 53 Yet, their findings were largely influenced by one study that reported a 7.5% linear increase in the risk of mortality after adjusting for numerous covariables including geographic locations.…”

Mortality Benefit Inconclusive, Based on This Review

“…Our group recently published a meta-analysis comparing severe sepsis/septic shock mortality in those who received antibiotics at < 1 h vs 1 to 3 h after arrival/onset. 2 We found no mortality difference between these two early times although antibiotic appropriateness was not our focus.…”

“…This biases toward no effect of delayed therapy. 2 We avoided this by studying appropriate or active antibiotic therapy. 3 Most studies included in our analysis defined delayed therapy as > 24 h because (1) delays this long are common (> 30% in the United States) 4 ; and (2) data from mixed septic/nonseptic populations suggest 24 to 48 h is the time threshold at which mortality increases the most.…”