Apramycin susceptibility of multidrug-resistant Gram-negative blood culture isolates in five countries in South-East Asia

Bloodstream infections (BSIs) are a leading cause of sepsis, a life-threatening condition that contributes significantly to the mortality of bacterial infections. Aminoglycoside antibiotics such as gentamicin or amikacin are essential medicines in the treatment of BSIs, but their clinical efficacy is increasingly compromised by antimicrobial resistance. The aminoglycoside apramycin has demonstrated preclinical efficacy against aminoglycoside- and multidrug-resistant (MDR) Gram-negative bacilli (GNB) and is currently in clinical development for the treatment of critical systemic infections. Here, we collected a panel of 470 MDR GNB isolates from health care facilities in Cambodia, Laos, Singapore, Thailand, and Vietnam for a multi-centre assessment of their antimicrobial susceptibility to apramycin in comparison to other aminoglycosides and colistin by broth microdilution assays. Apramycin and amikacin MICs ≤ 16 µg/mL were found for 462 (98.3%) and 408 (86.8%) GNB isolates, respectively. Susceptibility to gentamicin and tobramycin (MIC ≤ 4 µg/mL) was significantly lower at 122 (26.0%) and 101 (21.5%) susceptible isolates, respectively. Of note, all carbapenem- and third-generation cephalosporin (3GC) resistant Enterobacterales, all Acinetobacter baumannii, and all Pseudomonas aeruginosa isolates tested in this study appeared to be susceptible to apramycin. Of the 65 colistin-resistant isolates tested, only four (6.2%) had an apramycin MIC > 16 µg/mL. Apramycin demonstrated best-in-class activity against a panel of GNB isolates with resistances to other aminoglycosides, carbapenems, 3GC, and colistin, warranting continued consideration of apramycin as a drug candidate for the treatment of multidrug-resistant BSIs. Keywords: Bloodstream infection; Gram negative; aminoglycoside; antimicrobial resistance; apramycin; blood culture isolates