Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Clinical Laboratory, The Affiliated Peoples' Hospital of Ningbo University, Ningbo, Zhejiang, China.
Microbiol Spectr. 2023 Aug 17;11(4):e0221822. doi: 10.1128/spectrum.02218-22. Epub 2023 Jul 10.
Colistin has been considered a last-line option for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Heterogeneous resistance to colistin leads to unexplained clinical colistin treatment failure for CRKP. Our study aimed to investigate the extent of colistin heteroresistance among CRKP strains in China. A total of 455 colistin-susceptible strains, collected from six tertiary care hospitals in China, were characterized. The overall rate of colistin heteroresistance was 6.2%, as determined by the population analysis profiles (PAPs). Genomic analysis revealed that 60.7% of the colistin-heteroresistant isolates belonged to the epidemic sequence type 11 (ST11) clone. Single-nucleotide polymorphisms (SNPs) suggested that 6 ST5216 strains shared the same origin. Each of the subpopulations had a ≥8-fold decrease in colistin MIC in the presence of carbonyl cyanide -chlorophenylhydrazone (CCCP), which indicated that heteroresistance could be suppressed by an efflux pump inhibitor. In addition, our results suggested that the PhoPQ pathway plays an important role in the mechanisms of heteroresistance. The problem of CRKP has raised alarms concerning global health. Our study enriches the epidemiological study of colistin heteroresistance among CRKP strains in China, where the prevalence of this phenomenon was previously unknown. Importantly, colistin-heteroresistant strains may cause the failure of clinical treatment with colistin, even if the clinical laboratory reports that the strains are sensitive. The commonly used broth microdilution method is unable to detect this special phenomenon. Additionally, our results indicate that efflux pumps play a major role in colistin heteroresistance, and inhibitors can effectively reverse it. Our study is the first to provide a detailed analysis of the prevalence of colistin heteroresistance in China, as well as an analysis of the genetic mechanisms of this phenomenon.
黏菌素一直被认为是治疗碳青霉烯类耐药肺炎克雷伯菌（CRKP）感染的最后手段。黏菌素异质性耐药导致 CRKP 临床黏菌素治疗失败的原因不明。本研究旨在调查中国 CRKP 菌株中黏菌素异质性耐药的程度。从中国六家三级医院采集了 455 株对黏菌素敏感的菌株进行了特征分析。通过群体分析图谱（PAPs）确定，整体黏菌素异质性耐药率为 6.2%。基因组分析显示，60.7%的黏菌素异质性耐药分离株属于流行序列型 11（ST11）克隆。单核苷酸多态性（SNP）表明，6 株 ST5216 菌株具有相同的起源。在羰基氰化物-氯苯腙（CCCP）存在的情况下，每个亚群的黏菌素 MIC 均降低了≥8 倍，这表明异质性耐药可以被外排泵抑制剂抑制。此外，我们的结果表明 PhoPQ 途径在异质性耐药机制中起重要作用。CRKP 问题引起了全球健康的关注。本研究丰富了中国 CRKP 菌株中黏菌素异质性耐药的流行病学研究，此前中国对这一现象的流行情况尚不清楚。重要的是，即使临床实验室报告菌株敏感，黏菌素异质性耐药菌株也可能导致临床治疗失败。常用的肉汤微量稀释法无法检测到这种特殊现象。此外，我们的结果表明，外排泵在黏菌素异质性耐药中起主要作用，抑制剂可以有效逆转这种现象。本研究首次对中国黏菌素异质性耐药的流行情况进行了详细分析，并对这一现象的遗传机制进行了分析。
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