Sato Takumi, Ito Ryota, Kawamura Masato, Fujimura Shigeru
Division of Clinical Infectious Diseases & Chemotherapy, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Infect Drug Resist. 2022 Aug 23;15:4779-4784. doi: 10.2147/IDR.S375588. eCollection 2022.
Due to the spread of community-acquired methicillin-resistant (CA-MRSA), the demand for trimethoprim/sulfamethoxazole (SXT) is increasing in the world. It is not clear whether the resistant strain emerges by overuse of SXT. We investigated here the emergent risk of the SXT-resistant mutant in by an in vitro SXT exposure experiment.
A total of 40 clinical isolates (20 MSSA and 20 MRSA isolates) were exposed to sub-MIC of SXT for consecutive days, and MIC of SXT was determined every day. In addition, the DNA sequencing was performed to detect the mutation in the SXT-resistant strain.
The SXT-resistant strain began to emerge on the eighth day and accounted for 45% (18/40 clinical isolates) after 14 days. Moreover, one half of these resistant strains showed F98Y mutation in DfrB to retain SXT-resistance without selective pressure.
The emergent risk was SXT exposure of 14 days or more.
由于社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)的传播,世界范围内对甲氧苄啶/磺胺甲恶唑(SXT)的需求正在增加。目前尚不清楚耐药菌株是否因过度使用SXT而出现。我们在此通过体外SXT暴露实验研究了SXT耐药突变体出现的风险。
将总共40株临床分离株(20株甲氧西林敏感金黄色葡萄球菌和20株耐甲氧西林金黄色葡萄球菌分离株)连续数天暴露于低于最低抑菌浓度(sub-MIC)的SXT中,每天测定SXT的最低抑菌浓度(MIC)。此外,进行DNA测序以检测SXT耐药菌株中的突变。
SXT耐药菌株在第8天开始出现,14天后占45%(18/40株临床分离株)。此外,这些耐药菌株中有一半在二氢叶酸还原酶B(DfrB)中显示F98Y突变,从而在没有选择压力的情况下保持对SXT的耐药性。
出现耐药的风险是SXT暴露14天或更长时间。