Investigation of the In Vitro Effectiveness of Aztreonam/Avibactam, Colistin/Apramycin, and Meropenem/Apramycin Combinations Against Carbapenemase-Producing, Extensively Drug-Resistant Klebsiella pneumoniae Strains

Abstract

This study aimed at investigating the in vitro effectiveness of aztreonam/avibactam, colistin/avibactam, colistin/apramycin, and meropenem/apramycin combinations against carbapenemase-producing, extensively drug-resistant (XDR) Klebsiella pneumoniae strains. This study evaluated 38 carbapenem-resistant, carbapenemase-producing, and XDR K. pneumoniae strains. The checkerboard method was used to examine the efficacy of aztreonam/avibactam, and meropenem/apramycin combinations in all strains and the colistin/apramycin combination in colistin-resistant strains (n = 26). It was found that when used alone, aztreonam and avibactam had high minimum inhibitory concentration values in all strains and that all strains were resistant to aztreonam. Nevertheless, the aztreonam/avibactam combination was found to have a synergistic effect against all strains. Apramycin alone was effective against 30 K. pneumoniae strains (79%); however, 8 strains (21%) were found to be resistant. In the synergy testing of 26 colistin-resistant strains with the checkerboard method, the colistin/apramycin combination was found to have a synergistic effect against 4 strains (15.3%), an antagonistic effect against 8 strains (30.7%), and an additive effect against 14 strains (54%). By comparison, the meropenem/apramycin combination had a synergistic effect against 20 strains (52%) and an additive effect against 12 strains (31%). The aztreonam/avibactam combination showed a high in vitro synergistic effect on carbapenemase-producing and XDR K. pneumoniae strains, such as Metallo-beta-lactamase, and provided good prospects for the successful treatment. The meropenem/apramycin combination was also highly synergistic. The synergistic effects were low for the colistin/apramycin combination that was tested on colistin-resistant strains. However, it is promising that apramycin has low minimal inhibitory concentration values.