Mortality and delay in effective therapy associated with extended-spectrum -lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis

Abstract

OBJECTIVES: We performed a systematic review and meta-analysis to examine the impact of extended-spectrum beta-lactamase (ESBL) production on mortality and delay in effective therapy in Enterobacteriaceae bacteraemia. METHODS: We searched the PubMed database using the terms 'bacteremia or bloodstream' and 'ESBL or extended-spectrum beta-lactamase'. Included studies contained numbers of and mortality figures for patients with bacteraemia caused by ESBL producers and non-producers. Data extracted included crude relative risk (RR), adjusted odds ratio and 95% confidence intervals (CIs) for mortality and delayed effective therapy. Results were pooled using a random effects model. RESULTS: Sixteen studies met inclusion criteria. Meta-analysis of crude RRs demonstrated significantly increased mortality in ESBL-associated bacteraemia (pooled RR 1.85, 95% CI 1.39-2.47, P < 0.001). However, only one study reported RR controlled for confounding. Ten studies reported comparative data on delay in effective therapy. Meta-analysis of crude RRs demonstrated significantly increased incidence of delay in effective therapy in ESBL-associated bacteraemia (pooled RR 5.56, 95% CI 2.94-10.51, P < 0.001). CONCLUSIONS: In Enterobacteriaceae bacteraemia, ESBL production is associated with increased mortality and delay in effective therapy. However, lack of controlled studies limits interpretation regarding causality, and further controlled studies are required.