Ceftazidime-avibactam treatment dilemma of bla_KPC-2-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying bla_KPC-2 or bla_KPC-33 in lung transplant recipients.

IF 4.6 2区医学 Q1 MICROBIOLOGY

Annals of Clinical Microbiology and Antimicrobials Pub Date : 2024-11-08 DOI:10.1186/s12941-024-00743-x

Zichen Lei, Ziyao Li, Yulin Zhang, Lingbing Zeng, Yongli Wu, Feilong Zhang, Xinrui Yang, Xinmeng Liu, Qi Liu, Yiqun Ma, Binghuai Lu

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引用次数: 0

Abstract

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to immunocompromised populations, including lung transplant recipients. This study investigates mixed CRKP strains carrying either bla_KPC-2 or bla_KPC-33 following ceftazidime-avibactam (CAZ/AVI) exposure, particularly in the context of lung transplantation. Mixed CRKP strains with shifting resistance phenotypes were frequently identified in patients exposed to CAZ/AVI. We aimed to elucidate the transitional state of bla_KPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.

Methods: The bla_KPC-variant-carrying CRKP strains were collected from lung transplant recipients exposed to CAZ/AVI in less than two years. Antibiotic susceptibility testing (AST) was conducted using microbroth dilution, and whole-genome sequencing (WGS) was used to identify genotypes and resistance mechanisms. Limiting dilution, drop-plate, and in vitro induction experiments determined bla_KPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify bla_KPC-2 mutations.

Results: Among 104 lung transplant recipients infected by bla_KPC-harboring CRKP strains and receiving CAZ/AVI, 10 (9.6%) experienced changing resistance phenotypes. The limiting dilution method found that Patient 10's CRKP strains carried either bla_KPC-2 or bla_KPC-33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from bla_KPC-2 to bla_KPC-33.

Conclusions: The study identified a "transitional state" of the mixed CRKP strains carrying either bla_KPC-2 or bla_KPC-33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of bla_KPC variants, guiding treatment decisions in this complex landscape.

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肺移植受者中因携带 blaKPC-2 或 blaKPC-33 的混合菌株共存而导致的含 blaKPC-2 肺炎克雷伯菌的头孢唑肟-阿维巴坦治疗困境。

背景：耐碳青霉烯类肺炎克雷伯氏菌（CRKP）对包括肺移植受者在内的免疫功能低下人群构成重大威胁。本研究调查了暴露于头孢他啶-阿维巴坦（CAZ/AVI）后携带 blaKPC-2 或 blaKPC-33 的混合 CRKP 菌株，尤其是在肺移植的情况下。在暴露于 CAZ/AVI 的患者中经常发现耐药表型发生变化的混合 CRKP 菌株。我们旨在通过从肺移植患者中筛选出对CAZ/AVI敏感和耐药的CRKP菌株来阐明blaKPC变体的过渡状态：携带 blaKPC 变异株的 CRKP 菌株是从暴露于 CAZ/AVI 不到两年的肺移植受者身上采集的。采用微流稀释法进行抗生素药敏试验（AST），并通过全基因组测序（WGS）确定基因型和耐药机制。极限稀释、滴板和体外诱导实验确定了CAZ/AVI给药期间blaKPC变异体的变化：结果：在104例被携带blaKPC的CRKP菌株感染并接受CAZ/AVI治疗的肺移植受者中，有10例（9.6%）的耐药表型发生了变化。极限稀释法发现，患者10的CRKP菌株携带blaKPC-2或blaKPC-33。滴板实验显示了在 CAZ/AVI 培养基上的不同生长模式。体外诱导实验证明了 blaKPC-2 向 blaKPC-33 的转变：该研究发现，在接触过 CAZ/AVI 的患者中，携带 blaKPC-2 或 blaKPC-33 的混合 CRKP 菌株处于 "过渡状态"。分子诊断对于识别混合菌株和 blaKPC 变体的过渡状态至关重要，可在这种复杂的情况下指导治疗决策。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Clinical Microbiology and Antimicrobials MICROBIOLOGY-

CiteScore

8.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases. Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.