Abstract
This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89–1.20, I2 = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91–1.67, I2 = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72–1.04, I2 = 62%). In addition, no significant difference was observed in the subgroup analysis—high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84–1.21, I2 = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections.
Highlights
Carbapenem-resistance among gram-negative bacteria (GNB), including Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae, has significantly increased all over the world and poses a significant threat to public health [1,2,3]
This analysis based on five randomized controlled trials (RCTs) with 791 patients showed that the mortality of carbapenem-resistant GNB infections did not change significantly between colistin-based combination therapy and colistin monotherapy
In Zusman’s analysis of seven observational studies with 537 patients, colistin monotherapy was associated with an unadjusted odds ratio (OR) of 1.58 for mortality compared with a colistin–carbapenem combination [13]
Summary
Carbapenem-resistance among gram-negative bacteria (GNB), including Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae, has significantly increased all over the world and poses a significant threat to public health [1,2,3]. Clinical studies did not show consistent results regarding the synergistic effect of colistin-based combination therapy To unravel this controversial issue, two meta-analyses were conducted by Zusman et al [13] in 2017 and Vardakaset et al [14] in 2018, respectively. In these two meta-analyses, most of the enrolled studies were retrospective observational studies, and only three randomized controlled trials (RCTs) [15,16,17] were enrolled. We performed a comprehensive and updated meta-analysis of these five RCTs to provide better evidence of the efficacy of colistin monotherapy and colistin-based combination therapy on treating carbapenem-resistant bacteria infections
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