Polymyxins combined with other antibiotics for the treatment of multi-resistant Gram negative bacteria: review of the literature

Abstract

Background and aims: The emergence of infections due to multi resistant Gram negative bacteria is a major public- health concern worldwide. Polymyxins (colistin and polymyxin B) are among the last available options for the treatment of these infections. However, when used in monotherapy, the development of polymyxin resistant strains and high mortality rates of patients has been observed. Combination of polymyxins with other antibiotic drug classes may lead to synergism enhancing its bactericidal effect and reducing the emergence of resistant strains. This review aims to analyze the main in vitro and clinical studies assessing the potential benefit of combination therapy with this class of drugs.
Methods: We searched on PUBMED database for the mesh terms: “polymyxins”, “polymyxin B”, “colistin”, “combination therapy” and their combinations. Articles published in the last 10 years (2005-2015), in English language, evaluating combination therapy of other antimicrobial classes with polymyxins were included for analyses.
Results: Thirty-one’ articles were selected for review. In vitro studies evaluated combinations with beta-lactams, tigecycline, rifampicin, quinolones, chloramfenicol, vancomycin and daptomycin. Clinical studies evaluated the benefit of different combinations in the treatment of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa infections.
Conclusion: Polymyxin combinations regimens seem potentially advantageous in the treatment of multi-resistant Gram-negative bacteria. Combination with beta-lactams, especially carbapenems, were the most studied and yielded positive results. However, data evaluating its benefit are mostly from in vitro and observational studies. Results are not yet conclusive and randomized clinical trials accessing this strategy are urgently needed.
Key-Words: polymyxins, polymyxin B, colistin, combination therapy.