Synergistic combinations of polymyxins

- This is a review of recent in vitro, in vivo and clinical studies of polymyxin synergy.
- In vitro, many polymyxin combinations displayed synergistic killing.
- Animal studies offered limited evidence for the use of polymyxin combinations.
- Clinical studies provided divergent findings on the use of polymyxin combinations.
- Large clinical trials are underway to clarify the use of polymyxin combinations.

The proliferation of extensively drug-resistant Gram-negative pathogens has necessitated the therapeutic use of colistin and polymyxin B. However, treatment failures with polymyxin monotherapies and the emergence of polymyxin resistance have catalysed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and -resistant organisms. This mini-review examines recent (2011-2016) in vitro and in vivo studies that have attempted to identify synergistic polymyxin combinations against Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Clinical evidence for the use of combination regimens is also discussed.