Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium.
Genes (Basel). 2023 Jul 10;14(7):1426. doi: 10.3390/genes14071426.
Colistin heteroresistance has been identified in several bacterial species, including and , and may underlie antibiotic therapy failures since it most often goes undetected by conventional antimicrobial susceptibility tests. This study utilizes population analysis profiling (PAP) and time-kill assay for the detection of heteroresistance in and for evaluating the association between in vitro regrowth and heteroresistance. The mechanisms of colistin resistance and the ability of combination therapies to suppress resistance selection were also analysed. In total, 3 (18%) of the 16 colistin-susceptible strains (MIC ≤ 2 mg/L) were confirmed to be heteroresistant to colistin by PAP assay. In contrast to the colistin-susceptible control strains, all three heteroresistant strains showed regrowth when exposed to colistin after 24 h following a rapid bactericidal action. Colistin resistance in all the resistant subpopulations was due to the disruption of the gene by various insertion elements such as IS of the IS family and IS of the IS family. Colistin combined with carbapenems (imipenem, meropenem), aminoglycosides (amikacin, gentamicin) or tigecycline was found to elicit in vitro synergistic effects against these colistin heteroresistant strains. Our experimental results showcase the potential of combination therapies for treatment of infections associated with colistin heteroresistance.
粘菌素异质性耐药已在多种细菌物种中被发现，包括 和 ，并且可能是抗生素治疗失败的基础，因为它通常无法通过常规抗菌药物敏感性测试检测到。本研究利用群体分析轮廓（PAP）和时间杀伤试验来检测 和 中的异质性耐药，并评估体外再生长与异质性耐药之间的关联。还分析了粘菌素耐药的机制以及联合治疗抑制耐药选择的能力。在总共 16 株粘菌素敏感的菌株（MIC ≤ 2 mg/L）中，有 3 株（18%）通过 PAP 试验被确认为粘菌素异质性耐药。与粘菌素敏感的对照菌株不同，所有三种异质性耐药菌株在经历快速杀菌作用 24 小时后暴露于粘菌素时都显示出再生长。所有耐药亚群的粘菌素耐药性是由于 基因被各种插入元件（如 IS 家族的 IS 和 IS 家族的 IS）破坏所致。粘菌素与碳青霉烯类（亚胺培南、美罗培南）、氨基糖苷类（阿米卡星、庆大霉素）或替加环素联合使用被发现对这些粘菌素异质性耐药菌株具有体外协同作用。我们的实验结果展示了联合治疗在治疗与粘菌素异质性耐药相关的 感染方面的潜力。
