A systematic review and meta-analysis of treatment outcomes following antibiotic therapy among patients with carbapenem-resistant Klebsiella pneumoniae infections

Abstract

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major global public health challenge. This study aimed to systematically review the evidence on treatment outcomes (mortality, clinical and microbiological response) following antibiotic therapy administered for CRKP infections.

Methods: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts databases were searched from inception to 26 December 2018. Data were analysed via meta-analysis techniques using random-effects (DerSimonian and Laird) modelling.

Results: Fifty-four observational studies involving 3195 CRKP-infected patients who received antibiotic treatment were included. The pooled mortality, clinical and microbiological response rates were 37.2% (95% confidence interval [CI] 33.1-41.4%), 69.0% (95% CI 60.1-78.2%) and 63.7% (95% CI 53.7-74.1%), respectively. Compared with combination therapy, monotherapy was associated with a higher likelihood of mortality (odds ratio [OR] 1.45, 95% CI 1.18-1.78%), but there were no statistically significant differences in the likelihood of achieving clinical and microbiological responses. There were no statistically significant differences in the pooled likelihood of mortality, clinical or microbiological responses between two-drug and three-or-more-drug combination therapies or combination-containing and combination-sparing regimens of polymyxins, tigecycline, aminoglycosides and carbapenems. Moreover, clinical outcomes did not significantly differ among the various monotherapies.

Conclusions: These data highlight the need for systematic studies and well-designed randomised clinical trials to identify and evaluate the most appropriate antibiotic therapies for CRKP infections towards informing clinical decision-making. Furthermore, continuous surveillance of antimicrobial susceptibility patterns at local, regional, and national/international levels are important to support empirically-based therapy until susceptibility results for the isolate from the patient are available.

Keywords: Antibiotic resistance; Carbapenem resistance; Combination therapy; Infectious diseases; Klebsiella pneumoniae; Meta-analysis.