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.