Association between Carbapenem Resistance and Mortality among Adults Hospitalized with Serious Infections due to an Enterobacteriaceae spp: Results of a Systematic Literature Review and Meta-Analysis

Background:

Recent evidence suggests that the incidence of infections due to carbapenem-resistant (CR) Enterobacteriaceae spp (CRE) is on the rise worldwide. Published data regarding mortality associated with CRE are limited. This study sought to quantify mortality associated with serious infections caused by CRE and carbapenem-susceptible (CS) Enterobacteriaceae (CSE).

Methods:

A systematic literature review was performed using studies indexed by MEDLINE, Embase, and Cochrane databases between January 1, 1994, and December 1, 2015. The search algorithm included keywords for carbapenem resistance and mortality paired with terms for Gram-negative infections and pathogens. Mortality odds ratios were calculated through meta-analysis for the following: (1) CRE vs CSE infections, (2) CRE vs CSE blood stream infections, (3) CR Klebsiella pneumoniae vs. CS K. pneumoniae, and (4) K. pneumoniae carbapenemase (KPC)‒producing CRE vs CSE infections (because of the prevalence and distribution of KPC). The meta-analysis was conducted using a fixed-effects model. Heterogeneity was quantified using classical methods (ie, Cochran’s Q and the i² measure).

Results:

In total, 12 studies with mortality data for CRE vs CSE populations were identified (Figure 1). Compared with CSE, CRE was associated with a significantly higher risk of overall mortality, with an odds ratio of 3.39 (95% credible interval, 2.35–4.89). Heterogeneity was moderate (i²=45.5%, Qp=0.041). This association was also consistently found in subgroups analyzed, where point estimates showed that patients with carbapenem resistance were 2- to 3-fold more likely to die compared with patients with susceptible infections.

Conclusion:

These results document the increased mortality associated with serious CRE infections, compared with those that are susceptible to carbapenems, among adults in the hospital setting. It should be noted that the studies included were published before December 2015. It will be important to reevaluate the mortality in both CRE and CSE populations, especially among patients who receive early appropriate therapy, as new antibiotic therapies have recently become available.