Colistin Monotherapy versus Colistin plus Meropenem Combination Therapy for the Treatment of Multidrug-Resistant Acinetobacter baumannii Infection: A Meta-Analysis

Abstract

(1) Introduction: Colistin combination therapy with other antibiotics is a way to enhance colistin activity. The purpose of this meta-analysis was to compare the efficacy and safety of treatment with colistin monotherapy versus colistin plus meropenem combination therapy in patients with drug-resistant Acinetobacter baumannii infection. (2) Methods: All studies were included if they reported one or more of the following outcomes: clinical improvement, complete microbiological response, 14-day mortality, hospital mortality, or nephrotoxicity. (3) Results: Three randomized controlled trials and seven retrospective studies were included in the meta-analysis. Colistin monotherapy has similar rates of clinical improvement, 14-day mortality, hospital mortality, and nephrotoxicity as colistin plus meropenem combination therapy. Regarding complete microbiological response, the colistin plus meropenem combination was better than colistin monotherapy. (4) Discussion: Previous meta-analyses demonstrated heterogeneity in study quality and a lack of evidence supporting the use of colistin-based combination therapy. Our meta-analysis clearly showed that colistin combined with meropenem was not superior to colistin monotherapy for the treatment of Acinetobacter baumannii infection. (5) Conclusions: The efficacy and safety of treatment with colistin monotherapy and that of colistin plus meropenem combination therapy in patients with drug-resistant Acinetobacter baumannii infection were comparable. The majority of the evidence was obtained from nonrandomized studies, and high-quality randomized controlled trials are needed to confirm the role of colistin plus meropenem combination therapy in the treatment of multidrug-resistant Acinetobacter baumannii infection.

Keywords: Acinetobacter baumannii; colistin; combination therapy; meropenem; multidrug-resistant.

Figure 1

Flow diagram of the study process. Ten studies were included in the meta-analysis. Three were RCTs, and seven were retrospective observational studies.

Figure 2

Risk of bias of three randomized controlled trials [26,29,30].

Figure 3

Forest plots and funnel plots for clinical improvement between colistin monotherapy and colistin plus meropenem combination therapy. Nine studies involving 1484 patients (660 with colistin monotherapy, 824 with colistin plus meropenem combination therapy) reported clinical improvement. There was no significant difference in clinical improvement between patients treated with colistin monotherapy and colistin plus meropenem combination therapy [23,24,25,26,27,28,30,31,32].

Figure 4

Forest plots and funnel plots for microbiological response between colistin monotherapy and colistin plus meropenem combination therapy. Five studies involving 655 patients (285 with colistin monotherapy, 370 with colistin plus meropenem combination therapy) reported the microbiological response. The overall microbiological response was significantly different between the two groups. The combination therapy patient group had a better microbiological response than the monotherapy patient group [24,25,28,31,32].

Figure 5

Forest plots and funnel plots for 14-day mortality between colistin monotherapy and colistin plus meropenem combination therapy. Five studies involving 949 patients (441 with colistin monotherapy, 508 with colistin plus meropenem combination therapy) reported 14-day mortality. There was no significant difference in 14-day mortality between patients treated with colistin monotherapy and colistin plus meropenem combination therapy [24,26,27,28,30].

Figure 6

Forest plots and funnel plots for hospital mortality improvement between colistin monotherapy and colistin plus meropenem combination therapy. Seven studies involving 1269 patients (596 with colistin monotherapy, 673 with colistin plus meropenem combination therapy) reported hospital mortality or 28-day mortality. There was no significant difference in hospital mortality or 28-day mortality between patients treated with colistin monotherapy and colistin plus meropenem combination therapy [24,25,26,28,29,31,32].

Figure 7

Forest plots and funnel plots for nephrotoxicity between colistin monotherapy and colistin plus meropenem combination therapy. Data regarding nephrotoxicity were reported in four studies including 535 patients (235 with colistin monotherapy, 300 with colistin plus meropenem combination therapy). There was no significant difference in nephrotoxicity between patients treated with colistin monotherapy and colistin plus meropenem combination therapy [24,25,31,32].