Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Antimicrob Agents Chemother. 2019 Apr 25;63(5). doi: 10.1128/AAC.00040-19. Print 2019 May.
To assess the potential for the induction of antimicrobial resistance following repeated subinhibitory exposures to the combination minocycline (MIN), rifampin (RIF), and chlorhexidine (CHX), a total of 29 clinical microbial pathogenic isolates were repeatedly exposed to subinhibitory concentrations of MIN, RIF, and CHX for 20 passages. MICs of the MIN, RIF, and CHX combination were assessed at each passage to evaluate the potential for resistance to have been induced. The combination of MIN, RIF, and CHX showed significant antimicrobial efficacy and synergy against organisms resistant to all 3 individual components (MIC of ≥16 μg/ml for MIN or MIC of ≥4 μg/ml for RIF or CHX). Among the organisms originally resistant to 2 or more individual components and the organisms originally susceptible to 2 or more individual components, there was no evidence that organisms became resistant following 20 repeated subinhibitory exposure cycles to the triple combination. The risk of resistance developing to the triple combination is extremely low because microbes are inhibited or killed before resistance can simultaneously emerge to all three agents. Surveillance studies monitoring the development of resistance should be conducted in a clinical setting.
为了评估在反复接触亚抑菌浓度的米诺环素（MIN）、利福平（RIF）和洗必泰（CHX）组合后诱导抗菌耐药性的可能性，共对 29 种临床微生物病原体分离物进行了 20 轮的亚抑菌浓度 MIN、RIF 和 CHX 的重复暴露。在每次传代时评估 MIN、RIF 和 CHX 组合的 MIC，以评估是否已经诱导了耐药性。MIN、RIF 和 CHX 的组合对所有 3 种单独成分均具有抗微生物疗效和协同作用（MIN 的 MIC 为 ≥16 μg/ml 或 RIF 或 CHX 的 MIC 为 ≥4 μg/ml）。在最初对 2 种或更多种单独成分耐药的生物体和最初对 2 种或更多种单独成分敏感的生物体中，没有证据表明在 20 轮重复的亚抑菌暴露循环后，生物体对三联组合产生了耐药性。由于微生物在同时对所有三种药物产生耐药性之前就被抑制或杀死，因此对三联组合产生耐药性的风险极低。应在临床环境中进行监测耐药性发展的监测研究。
