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<p>Infections caused by Carbapenem-Resistant <i>Klebsiella pneumoniae</i> (CRKP) have become a serious threat to global public health. We reported fatal infections associated with <i>Klebsiella pneumoniae</i> (KP) and revealed the evolution of in-host drug resistance that occurred during tigecycline, eravacycline and Polymyxin B treatments. In this study, six strains of KP were isolated from one patient with liver cirrhosis and chronic liver failure. Among them, one strain is Carbapenem-Sensitive <i>Klebsiella pneumoniae</i> (CSKP) and five strains are CRKP cloned from ST11-KL64. Polymyxin B drug sensitivity tests were conducted on strains d5, d13, d15, d17 and d21. It was found that d5 and d15 were sensitive to Polymyxin B, while strains d13, d17 and d21 were resistant to Polymyxin B. The results of drug sensitivity were consistent with the expression level of the colistin resistance gene <i>pmrB</i> and also consistent with the SNP difference results of <i>pmrB</i> in these five strains. These results further prove that the mutation site of the Polymyxin B <i>pmrB</i> resistance gene in this study is the Thr mutation at position 469 to Pro, which is a new mutation mechanism of the Polymyxin B resistance gene. The drug sensitivity results of eravacycline and tigecycline were consistent with their SNP difference results. It was found that position 523 on the ABC efflux pump system mutated from Ala to Thr, suggesting that the evolution of drug resistance of tigecycline and eravacycline may be related to the ABC efflux pump. The results indicated that <i>Klebsiella pneumoniae</i> witnessed the evolution of drug resistance in the host during the treatment with Polymyxin B, eravacycline and tigecycline, posing a potential threat to clinical anti-infective treatment.</p>

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Analysis of the evolution mechanism of in-host drug resistance of Klebsiella pneumoniae during treatment with tigecycline, eravacycline and Polymyxin B

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月6日

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  • Jianhua Fang,
  • Miao Deng,
  • Zhongmin Li,
  • Hongyi Lai,
  • Rongfan Lai,
  • Huade Chen,
  • Zucan Luo,
  • Zhibo Tao,
  • Na Cheng,
  • Tianxin Xiang

摘要

Infections caused by Carbapenem-Resistant Klebsiella pneumoniae (CRKP) have become a serious threat to global public health. We reported fatal infections associated with Klebsiella pneumoniae (KP) and revealed the evolution of in-host drug resistance that occurred during tigecycline, eravacycline and Polymyxin B treatments. In this study, six strains of KP were isolated from one patient with liver cirrhosis and chronic liver failure. Among them, one strain is Carbapenem-Sensitive Klebsiella pneumoniae (CSKP) and five strains are CRKP cloned from ST11-KL64. Polymyxin B drug sensitivity tests were conducted on strains d5, d13, d15, d17 and d21. It was found that d5 and d15 were sensitive to Polymyxin B, while strains d13, d17 and d21 were resistant to Polymyxin B. The results of drug sensitivity were consistent with the expression level of the colistin resistance gene pmrB and also consistent with the SNP difference results of pmrB in these five strains. These results further prove that the mutation site of the Polymyxin B pmrB resistance gene in this study is the Thr mutation at position 469 to Pro, which is a new mutation mechanism of the Polymyxin B resistance gene. The drug sensitivity results of eravacycline and tigecycline were consistent with their SNP difference results. It was found that position 523 on the ABC efflux pump system mutated from Ala to Thr, suggesting that the evolution of drug resistance of tigecycline and eravacycline may be related to the ABC efflux pump. The results indicated that Klebsiella pneumoniae witnessed the evolution of drug resistance in the host during the treatment with Polymyxin B, eravacycline and tigecycline, posing a potential threat to clinical anti-infective treatment.