Combination therapy with polymyxin B and netropsin against clinical isolates of multidrug-resistant Acinetobacter baumannii.

Abstract

Polymyxins are last-resort antibiotics for treating infections of Gram-negative bacteria. The recent emergence of polymyxin-resistant bacteria, however, urgently demands clinical optimisation of polymyxin use to minimise further evolution of resistance. In this study we developed a novel combination therapy using minimal concentrations of polymyxin B. After large-scale screening of Streptomyces secondary metabolites, we identified a reliable polymixin synergist and confirmed as netropsin using high-pressure liquid chromatography, nuclear magnetic resonance, and mass spectrometry followed by in vitro assays using various Gram-negative pathogenic bacteria. To evaluate the effectiveness of combining polymixin B and netropsin in vivo, we performed survival analysis on greater wax moth Galleria mellonella infected with colistin-resistant clinical Acinetobacter baumannii isolates as well as Escherichia coli, Shigella flexineri, Salmonella typhimuruim, and Pseudomonas aeruginosa. The survival of infected G. mellonella was significantly higher when treated with polymyxin B and netropsin in combination than when treated with polymyxin B or netropsin alone. We propose a netropsin combination therapy that minimises the use of polymyxin B when treating infections with multidrug resistant Gram-negative bacteria.

• Authors: Joon-Hui Chung, Abhayprasad Bhat, Chang-Jin Kim, Dongeun Yong, Choong-Min Ryu
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 28168 (06 16 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27306928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Netropsin
• Polymyxin B

Topics

• Acinetobacter Infections (drug therapy, microbiology)
• Acinetobacter baumannii (drug effects, isolation & purification)
• Animals
• Anti-Bacterial Agents (therapeutic use)
• Drug Resistance, Multiple, Bacterial (physiology)
• Drug Synergism
• Drug Therapy, Combination
• Escherichia coli (drug effects)
• Humans
• Microbial Sensitivity Tests
• Models, Animal
• Moths (microbiology)
• Netropsin (therapeutic use)
• Polymyxin B (therapeutic use)
• Pseudomonas aeruginosa (drug effects)
• Salmonella typhimurium (drug effects)
• Shigella flexneri (drug effects)