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

•Apramycin is an aminoglycoside approved for veterinary use.•Activity against highly drug resistant P. aeruginosa and A. baumannii was studied.•MIC values were lower for apramycin than for amikacin, gentamicin, and tobramycin.•Frank apramycin resistance is very rare among Acinetobacter and Pseudomonas.•Apramycin could potentially be repurposed against highly drug-resistant pathogens.

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 μg/ml for A. baumannii and 16/32 μg/ml for P. aeruginosa. Only 2% of A. baumannii and P. aeruginosa had an MIC greater than an epidemiological cutoff value of 64 μg/ml. In contrast, the MIC50/MIC90 for amikacin, gentamicin, and tobramycin were ≥64/>256 μg/ml for A. baumannii with 57%, 95%, and 74% of isolates demonstrating resistance, respectively, and the MIC50/MIC90 were ≥8/256 μg/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.