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-β-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.

中文翻译：

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氨曲南/阿维巴坦、粘菌素/安普霉素和美罗培南/安普霉素组合对产碳青霉烯酶、广泛耐药肺炎克雷伯菌菌株的体外有效性研究。


本研究旨在研究氨曲南/阿维巴坦、粘菌素/阿维巴坦、粘菌素/安普霉素和美罗培南/安普霉素组合对产生碳青霉烯酶的广泛耐药 (XDR)肺炎克雷伯菌菌株的体外有效性。本研究评估了 38 种耐碳青霉烯类、产碳青霉烯酶和 XDR肺炎克雷伯菌菌株。采用棋盘法检验氨曲南/阿维巴坦、美罗培南/安普霉素组合对所有菌株的疗效以及粘菌素/安普霉素组合对粘菌素耐药菌株的疗效（ n = 26）。结果发现，单独使用时，氨曲南和阿维巴坦在所有菌株中均具有较高的最低抑菌浓度值，并且所有菌株均对氨曲南产生耐药性。然而，发现氨曲南/阿维巴坦组合对所有菌株都具有协同作用。单独使用安普霉素可有效对抗 30株肺炎克雷伯菌菌株（79%）；然而，8 个菌株（21%）被发现具有耐药性。采用棋盘法对26株粘菌素耐药菌株进行协同试验，发现粘菌素/安普霉素组合对4株菌株（15.3%）有协同作用，对8株菌株（30.7%）有拮抗作用，有相加作用对抗 14 种菌株（54%）。相比之下，美罗培南/安普霉素组合对20种菌株（52%）具有协同作用，对12种菌株（31%）具有相加作用。氨曲南/阿维巴坦组合对产碳青霉烯酶和 XDR肺炎克雷伯菌菌株（如金属-β-内酰胺酶）显示出高度的体外协同作用，为成功治疗提供了良好的前景。美罗培南/安普霉素组合也具有高度协同作用。 在粘菌素抗性菌株上测试的粘菌素/安普霉素组合的协同效应较低。然而，安普霉素具有较低的最低抑制浓度值，这是有希望的。