Impact of third-generation cephalosporin and carbapenem resistance profiles on the mortality of patients with Enterobacter cloacae complex bloodstream infections: a retrospective multicentre cohort study.

OBJECTIVES

To evaluate 30-day mortality in Enterobacter cloacae complex (Ecc) bloodstream infections (BSIs) according to third-generation cephalosporin and carbapenem resistance profiles, and to investigate factors contributing to the association between antimicrobial resistance and this outcome.

METHODS

Multicentre retrospective cohort including adults with healthcare-associated Ecc BSI from four Brazilian tertiary hospitals. Isolates were categorized as: third-generation cephalosporin-susceptible (3GCS), third-generation cephalosporin-resistant (3GCR), or carbapenem-resistant (CR). A hierarchical Cox model assessed the effect of resistance profiles on 30-day mortality, adjusting sequentially for: (i) baseline status, (ii) BSI-related variables and (iii) antimicrobial therapy.

RESULTS

Of 429 patients, 300 (69.9%) had 3GCS, 103 (24.0%) 3GCR and 26 (6.1%) CR Ecc BSIs. Thirty-day mortality was 22.6% (20.6%, 25.2% and 34.6%, respectively; P = 0.20). In unadjusted analysis, 3GCR (HR 1.10; 95% CI 0.70-1.73) and CR (HR 1.42; 95% CI 0.70-2.86) were not significantly associated with mortality. Hierarchical adjustment revealed that the association between CR and mortality was attenuated after adjustment for baseline severity, while adjustment for appropriate therapy attenuated the associations observed for both resistance profiles. Higher Charlson and Pitt scores, lower baseline glomerular filtration rate and polymicrobial BSI were independently associated with higher mortality; adequate therapy at any time was strongly protective.

CONCLUSIONS

Non-statistically significant mortality rates were observed in patients with 3GCR and CR Ecc BSIs. Baseline severity and, most importantly, less frequent appropriate antimicrobial therapy attenuated the effect of resistance profiles on the outcome. Improving antimicrobial therapy against resistant Ecc isolates has great potential to reduce mortality.