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塞菲德罗科尔的活性受到Pseudomonas aeruginosa中获得的扩展光谱氧化酶的影响

Xavier Vuillemin¹, Maëlle Da Silva², Maxime Bour²

¹Laboratoire de Bactériologie, Centre Hospitalier Universitaire de Besançon, Besançon, France; Laboratoire Associé au Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Besançon, Besançon, France; Chrono-environnement, Université Bourgogne-Franche Comté, Besançon, France.

International journal of antimicrobial agents

|July 10, 2023

概括

Pseudomonas aeruginosa 中的一些扩展谱氧酶 (ES-OXA) 降低了对 cefiderocol 的敏感性. 这些β-乳糖酶的特定突变与较新的类的活性下降有关.

科学领域:

微生物学微生物学
抗微生物耐药性抗微生物耐药性
酶动力学酶动力学

背景情况:

塞菲德罗科尔在Pseudomonas aeruginosa的体外表现出强大的活性.
然而,β-乳酸酶的产生可以在一些P. aeruginosa分离物中产生抗性.
已获得的扩展谱氧酶 (ES-OXA) 对醇敏感性的影响仍未评估.

研究的目的:

调查P. aeruginosa中常见的ES-OXA酶是否会影响对 cefiderocol.的敏感性.
为了识别与降低 cefiderocol 活性相关的特定 ES-OXA 变异和突变.

主要方法:

从主要的P. aeruginosa亚群中克隆了18个OXA基因,并将其转化为pUCP24穿载体.
用克隆的OXA基因转化了参考菌株PAO1.
在产生的转化剂中评估了 cefiderocol 最低抑制度 (MIC).

主要成果:

OXA-2,OXA-46和某些OXA-10亚群酶显著降低了塞菲德罗尔的敏感性 (降低了8到32倍).
在 Ω 循环 (例如,OXA-2 中的 Ala149Pro,Asp150Gly;OXA-10 中的 Trp154Cys,Gly157Asp) 和 β5-β6 循环中的特定突变与敏感性降低有关.
在临床菌株中,常见的ES-OXA,OXA-19,与其他类素一起,损害了 cefiderocol 活性.

结论:

几种ES-OXA酶显著影响P. aeruginosa.中基的敏感性.
在ES-OXA中发生的Trp154Cys和Gly157Asp等突变令人担忧,因为它们与针对P. aeruginosa的新型头素活性降低有关.

关键词:

在Cefiderocol的耐药性.氧酸酸盐的存在伪omonas aeruginosa 这种类型的病毒.

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