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

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.