Multi-drug resistant A. baumannii is a major concern due to the limited treatment options and the poor outcomes associated with it. Several in vitro and observational studies suggest a synergistic activity between colistin and rifampicin against multi-drug resistant A. baumannii.1-7
Aydemir and colleagues8 recently published the first randomized controlled study to evaluate the efficacy of colistin alone vs. the combination of colistin and rifampicin in patients with ventilator-associated pneumonia (VAP) due to carbapenem-resistant A. baumannii (CRAB). Eligible patients were ≥18 y.o. with VAP due to CRAB within 48 hrs after the onset of pneumonia. Patients with polymicrobial cultures or who had another infection due to a different microorganism were excluded.
Patients were randomized to receive colistin or colistin with rifampicin (600 mg orally/day). The dose of colistin base was 300 mg/day (equivalent to 9 mu colistin methanesulfonate), divided into 3 doses, or an adjusted dose in patients with renal failure. Empirical antimicrobial therapy was initiated as soon as the diagnosis of VAP was made. The infection disease specialist who conducted daily follow-up of patients determined the treatment duration. The primary outcome was the clinical response of VAP, while the secondary endpoints were microbiological, laboratory, and radiological responses.
Over the study period, 43 patients were enrolled. Although the clinical, laboratory, radiological, and microbiological responses were lower in the combination group, compared to the colistin only group, none of the end points reached statistical significance. The mean number of days to microbiological clearance was lower in the combination group, compared to the colistin only group (3.1 vs. 4.5, p=0.029), but there was no statistically significant difference between the two groups in the in-hospital and VAP-related mortality.
The study suggests that combined colistin and rifampicin therapy may improve outcomes in patients with VAP due to CRAB. However, the study has several limitations including the small sample size, the low statistical power, and being in a single-center. In addition, the study used rifampicin in an oral instead of the intravenous dosage form, which could be a problem in critically ill patients with impaired absorption. Furthermore, none of the patients received inhaled colistin therapy.
It should also be noted that the diagnosis of VAP and the evaluation of the outcomes in critically ill patients with other underlying comorbidities may be difficult. The current available evidence does not yet fully support combination therapy due to the limitations mentioned above regarding the study by Aydemir et al. and the limitations of the in vitro and observational studies. Large controlled studies are needed to demonstrate the value of combination therapy.
1. Tascini C, Menichetti F, Bozza S, et al. Evaluation of the activities of two-drug combinations of rifampicin, polymyxin B and ampicillin/sulbactam against Acinetobacter baumannii. J of Antimicrob Chemother 1998;42:270-71.
2. Song JY, Kee SY, Hwang IS, et al. In vitro activities of carbapenem/sulbactam combination, colisin, colistin/rifampicin combination ...