In vitro Apramycin Activity against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa

The in vitro activity of apramycin was compared to that of amikacin, gentamicin, and tobramycin against multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Apramycin demonstrated an MIC50/MIC90 of 8/32 mu g/ml for A. baumannii and 16/32 mu g/ml for P. aeruginosa. Only 2% of A. baumannii and P. aeruginosa had an MIC greater than an epidemiological cutoff value of 64 mu g/ml. In contrast, the MIC50/MIC90 for amikacin, gentamicin, and tobramycin were >= 64/>256 mu g/ml for A. baumannii with 57%, 95%, and 74% of isolates demonstrating resistance, respectively, and the MIC50/ MIC90 were >= 8/256 mu g/ml for P. aeruginosa with 27%, 50%, and 57% of strains demonstrating resistance, respectively. Apramycin appears to offer promising in vitro activity against highly resistant pathogens. It therefore may warrant further pre-clinical study to assess potential for repurposing as a human therapeutic and relevance as a scaffold for further medicinal chemistry exploration. (C) 2017 Elsevier Inc. All rights reserved.