Determinants of inappropriate empirical antibiotic treatment: systematic review and meta-analysis

This systematic review assessed study-level determinants of non-covering (inappropriate) empirical antibiotic treatment (IEAT), focusing on the influence of study years and the prevalence of multidrug-resistant organisms (MDROs) in the study. Prospective and retrospective observational studies reporting on the association between IEAT and mortality in adult patients with microbiologically documented infections published between 2008–2016 were included. A meta-analysis of IEAT rates was conducted using a random-effects model. Subgroup analyses and mixed-effect single-covariate meta-regression were conducted to identify the association between clinical and methodological study-level covariates and IEAT rates. Heterogeneity was assessed using the I² measure of inconsistency. Multi-covariate meta-regression was conducted including variables with a P-value of <0.1 on single-covariate analysis. A total of 191 studies were included assessing 73 595 patients, most commonly with bacteraemia. The pooled IEAT event rate was 32% [95% confidence interval (CI) 30–35%], with large heterogeneity (I² = 97.7%). On multi-covariate analyses, the prevalence of any MDRO [odds ratio (OR) per 10% increase in prevalence = 1.11, 95% CI 1.07–1.15], Acinetobacter spp. specifically (OR = 1.99, 95% CI 1.22–3.25) and advancing study years were associated with IEAT rates (OR = 1.03, 95% CI 1.00–1.06 per year). MDRO rates were independently associated with mortality rates in the studies, adjusting to the rate of IEAT. The prevalence of MDROs, mainly multidrug-resistant Gram-negative bacteria, is significantly associated with the probability of prescribing IEAT and mortality rates in recent studies. We show how antibiotic resistance impacts patient management and outcomes.