{"title":"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。","authors":"Zichen Lei, Ziyao Li, Yulin Zhang, Lingbing Zeng, Yongli Wu, Feilong Zhang, Xinrui Yang, Xinmeng Liu, Qi Liu, Yiqun Ma, Binghuai Lu","doi":"10.1186/s12941-024-00743-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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<sub>KPC-2</sub> or bla<sub>KPC-33</sub> 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<sub>KPC</sub> variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.</p><p><strong>Methods: </strong>The bla<sub>KPC</sub>-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<sub>KPC</sub>-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify bla<sub>KPC-2</sub> mutations.</p><p><strong>Results: </strong>Among 104 lung transplant recipients infected by bla<sub>KPC</sub>-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<sub>KPC-2</sub> or bla<sub>KPC-33</sub>. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from bla<sub>KPC-2</sub> to bla<sub>KPC-33</sub>.</p><p><strong>Conclusions: </strong>The study identified a \"transitional state\" of the mixed CRKP strains carrying either bla<sub>KPC-2</sub> or bla<sub>KPC-33</sub> in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of bla<sub>KPC</sub> variants, guiding treatment decisions in this complex landscape.</p>","PeriodicalId":8052,"journal":{"name":"Annals of Clinical Microbiology and Antimicrobials","volume":"23 1","pages":"99"},"PeriodicalIF":4.6000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549737/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ceftazidime-avibactam treatment dilemma of bla<sub>KPC-2</sub>-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying bla<sub>KPC-2</sub> or bla<sub>KPC-33</sub> in lung transplant recipients.\",\"authors\":\"Zichen Lei, Ziyao Li, Yulin Zhang, Lingbing Zeng, Yongli Wu, Feilong Zhang, Xinrui Yang, Xinmeng Liu, Qi Liu, Yiqun Ma, Binghuai Lu\",\"doi\":\"10.1186/s12941-024-00743-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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<sub>KPC-2</sub> or bla<sub>KPC-33</sub> 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<sub>KPC</sub> variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.</p><p><strong>Methods: </strong>The bla<sub>KPC</sub>-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<sub>KPC</sub>-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify bla<sub>KPC-2</sub> mutations.</p><p><strong>Results: </strong>Among 104 lung transplant recipients infected by bla<sub>KPC</sub>-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<sub>KPC-2</sub> or bla<sub>KPC-33</sub>. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from bla<sub>KPC-2</sub> to bla<sub>KPC-33</sub>.</p><p><strong>Conclusions: </strong>The study identified a \\\"transitional state\\\" of the mixed CRKP strains carrying either bla<sub>KPC-2</sub> or bla<sub>KPC-33</sub> in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of bla<sub>KPC</sub> variants, guiding treatment decisions in this complex landscape.</p>\",\"PeriodicalId\":8052,\"journal\":{\"name\":\"Annals of Clinical Microbiology and Antimicrobials\",\"volume\":\"23 1\",\"pages\":\"99\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-11-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549737/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Clinical Microbiology and Antimicrobials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12941-024-00743-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Clinical Microbiology and Antimicrobials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12941-024-00743-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Ceftazidime-avibactam treatment dilemma of blaKPC-2-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying blaKPC-2 or blaKPC-33 in lung transplant recipients.
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 blaKPC-2 or blaKPC-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 blaKPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.
Methods: The blaKPC-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 blaKPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify blaKPC-2 mutations.
Results: Among 104 lung transplant recipients infected by blaKPC-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 blaKPC-2 or blaKPC-33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from blaKPC-2 to blaKPC-33.
Conclusions: The study identified a "transitional state" of the mixed CRKP strains carrying either blaKPC-2 or blaKPC-33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of blaKPC variants, guiding treatment decisions in this complex landscape.
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.
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