利福平联合多粘菌素 B 的最小有效抗生素浓度 (MEAC) 对广泛耐药、耐碳青霉烯类和耐多粘菌素 B 的肺炎克雷伯菌临床分离株的体外协同作用。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Nathália Abichabki, Gilberto Gambero Gaspar, Luísa Vieira Zacharias, Renata Helena Cândido Pocente, Denissani Aparecida Ferrari Santos Lima, Natália Augusta Barbosa de Freitas, Guilherme Thomaz Pereira Brancini, Natália Columbaro Moreira, Gilberto Úbida Leite Braga, Fernando Bellissimo-Rodrigues, Valdes Roberto Bollela, Ana Lúcia Costa Darini, Leonardo Neves Andrade
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引用次数: 0

摘要

我们研究了利福平 (RIF) + 多粘菌素 B (PB) 复方制剂对广泛耐药(XDR)肺炎克雷伯菌分离株的体外抗菌活性。我们评估了对 PB(非 mcr 携带者;eptB、mgrB、pmr 操作子和 ramA 突变)和碳青霉烯类(KPC、CTX-M 和 SHV 生产者;包括 KPC + NDM 共同生产者)共同耐药的临床分离株,它们属于 ST16、ST11、ST258、ST340 和 ST437 序列类型。我们使用标准肉汤微稀释法测定了 RIF 和 PB 的最低抑菌浓度 (MIC),并使用棋盘格试验评估了 RIF + PB 的抑菌浓度指数 (FICI),同时还研究了 RIF 和 PB 联合(RIF + PB)具有抗菌活性的最低浓度。进行了时间致死试验,以评估该组合对所选分离菌株的协同效应。测定了 PB MIC(32-256 µg/mL)和 RIF MIC(32-1024 µg/mL)。FICI (
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In Vitro Synergistic Activity of Rifampicin Combined with Minimal Effective Antibiotic Concentration (MEAC) of Polymyxin B Against Extensively Drug-Resistant, Carbapenem-, and Polymyxin B-Resistant Klebsiella pneumoniae Clinical Isolates.

We investigated the in vitro antibacterial activity of the combination rifampicin (RIF) + polymyxin B (PB) against extensively drug-resistant (XDR) Klebsiella pneumoniae isolates. We evaluated clinical isolates co-resistant to PB (non-mcr carriers; eptB, mgrB, pmr operon, and ramA mutations) and to carbapenems (KPC, CTX-M, and SHV producers; including KPC + NDM co-producer), belonging to sequence types (ST) ST16, ST11, ST258, ST340, and ST437. We used the standard broth microdilution method to determine RIF and PB minimum inhibitory concentration (MIC) and the checkerboard assay to evaluate the fractional inhibitory concentration index (FICI) of RIF + PB as well as to investigate the lowest concentrations of RIF and PB that combined (RIF + PB) had antibacterial activity. Time-kill assays were performed to evaluate the synergistic effect of the combination against selected isolates. PB MIC (32-256 µg/mL) and RIF MIC (32-1024 µg/mL) were determined. FICI (<0.5) indicated a synergistic effect for all isolates evaluated for the combination RIF + PB. Our results showed that low concentrations of PB (PB minimal effective antibiotic concentration [MEAC], ≤0.25-1 µg/mL) favor RIF (≤0.03-0.125 µg/mL) to reach the bacterial target and exert antibacterial activity against PB-resistant isolates, and the synergistic effect was also observed in time-kill results. The combination of RIF + PB showed in vitro antibacterial activity against XDR, carbapenem-, and PB-resistant K. pneumoniae and could be further studied as a potential combination therapy, with cost-effectiveness and promising efficacy.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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