The association between mortality and door-to-antibiotic time: a systematic review and meta-analysis

Abstract

Purpose: Previous studies evaluating the impact of antibiotic timing on mortality in sepsis have shown conflicting results. We performed a meta-analysis to evaluate the association between door-to-antibiotic time (each hour of delay) and mortality in sepsis.

Methods: We searched PubMed and Embase through 10 November 2022 to identity cohort studies that evaluated the adjusted association between door-to-antibiotic time (each hour of delay) and mortality in adult patients with sepsis. The primary outcome was mortality. Analysis was based on inverse-variance weighting using a fixed-effects model. The variances were derived from the logarithms of the reported confidence intervals (CIs) for associations. We estimated the odds ratio, 95% CI, and number needed to treat for the pooled data.

Results: Fifteen cohort studies involving 106 845 patients were included in the meta-analysis. Door-to-antibiotic time (each hour of delay) was associated with increased risk of mortality (odds ratio: 1.07; 95% CI: 1.06-1.08; P < 0.0001; number needed to treat = 91), with high heterogeneity (I2 = 82.2%). The association was robust in sensitivity analyses and consistent in subgroup analyses. No publication bias was found.

Conclusion: In adult patients with sepsis, each hour of delay in antibiotic administration is associated with increased odds of mortality. Key messages What is already known on this topic Sepsis is a common and lethal syndrome that affects millions of people worldwide. The updated 2018 Surviving Sepsis Campaign guidelines recommended initiating empirical broad-spectrum antibiotic coverage within 1 hour of identification of sepsis and septic shock. Delay in antibiotic administration may increase the risk of mortality in patients with sepsis. What this study adds This meta-analysis evaluates and quantifies the association between door-to-antibiotic time (each hour of delay) and mortality in patients with sepsis. Each hour of delay in antibiotic administration is associated with increased odds of mortality in sepsis. The number needed to treat (NNT) with delayed antibiotic administration for one additional death was 91. How this study might affect research, practice, or policy: More efforts should be made to speed up the diagnosis of sepsis or sepsis shock.

Keywords: antibiotics; meta-analysis; mortality; sepsis; time-to-treatment.