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

Introduction: Bloodstream infections (BSIs) are a leading cause of sepsis, which is a life-threatening condi-tion that significantly contributes 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 being compromised by antimicrobial resistance. The aminoglycoside apramycin has demon-strated preclinical efficacy against aminoglycoside-resistant and multidrug-resistant (MDR) Gram-negative bacilli (GNB) and is currently in clinical development for the treatment of critical systemic infections.Methods: This study collected a panel of 470 MDR GNB isolates from healthcare facilities in Cambodia, Laos, Singapore, Thailand and Vietnam for a multicentre assessment of their antimicrobial susceptibility to apramycin in comparison with other aminoglycosides and colistin by broth microdilution assays.Results: Apramycin and amikacin MICs <= 16 mu g/mL were found for 462 (98.3%) and 408 (86.8%) GNB isolates, respectively. Susceptibility to gentamicin and tobramycin (MIC <= 4 mu g/mL) was significantly lower at 122 (26.0%) and 101 (21.5%) susceptible isolates, respectively. Of note, all carbapenem and third-generation cephalosporin-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, four (6.2%) had an apramycin MIC > 16 mu g/mL.Conclusion: Apramycin demonstrated best-in-class activity against a panel of GNB isolates with resis-tances to other aminoglycosides, carbapenems, third-generation cephalosporins and colistin, warranting continued consideration of apramycin as a drug candidate for the treatment of MDR BSIs.(c) 2022 The Author(s). Published by Elsevier Ltd.This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

Apramycin demonstrated the best activity against multidrug-resistant Gram-negative bacilli (GNB) with resistance to other aminoglycosides, carbapenems, third-generation cephalosporins, and colistin, warranting further consideration of apramycin as a drug candidate for the treatment of multidrug-resistant bloodstream infections.