{"title":"Mechanisms and fitness of ceftazidime/avibactam-resistant Klebsiella pneumoniae clinical strains in Taiwan","authors":"","doi":"10.1016/j.ijantimicag.2024.107244","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) infection is a global public health issue, and ceftazidime/avibactam is recommended by international guidelines as the preferred treatment for KPC- and OXA-48-producing CRKP. Since its introduction in Taiwan in 2019, ceftazidime/avibactam-resistant strains have emerged. Our aim is to investigate the mechanisms of ceftazidime/avibactam resistance in CRKP in Taiwan and study their associated fitness costs.</p></div><div><h3>Methods</h3><p>Ceftazidime/avibactam-resistant CRKP strains with exposure to ceftazidime/avibactam isolated from clinical specimens were consecutively collected at Taipei Veterans General Hospital in 2020. The serial strains exhibiting ceftazidime/avibactam-susceptible and ceftazidime/avibactam-resistant phenotypes isolated from the same patient were characterized using whole-genome sequencing and tested for their growth rates and competitive abilities.</p></div><div><h3>Results</h3><p>A total of 35 ceftazidime/avibactam-resistant CRKP strains were identified, with 20 being metallo-β-lactamase producers. Ten strains harboured KPC variants, exhibiting MIC for ceftazidime/avibactam ranging from 64 to ≥256 mg/L. The 10 strains demonstrating high-level ceftazidime/avibactam resistance possessed mutated KPC variants: KPC-33 (<em>n</em> = 3), KPC-31 (<em>n</em> = 1), KPC-39 (<em>n</em> = 1), KPC-44 (<em>n</em> = 1), KPC-58 (<em>n</em> = 1), KPC-90 (<em>n</em> = 1), and two novel KPC variants. Ceftazidime/avibactam-resistant strains with KPC-33 and KPC-39 showed a significant fitness cost and lower growth rate compared to their parental strains. In contrast, ceftazidime/avibactam-resistant strains with KPC-58 and KPC-58 plus D179Y showed similar growth rates and competitive abilities compared to their parental strains.</p></div><div><h3>Conclusions</h3><p>Mutated KPC variants conferred high-level ceftazidime/avibactam resistance in Taiwan. Significant fitness costs were observed in both the ceftazidime/avibactam-resistant KPC-33 and KPC-39 strains. Despite conferring a similar level of ceftazidime/avibactam resistance, different KPC variants could entail varying degrees of fitness costs.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 2","pages":"Article 107244"},"PeriodicalIF":4.9000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Antimicrobial Agents","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0924857924001626","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a global public health issue, and ceftazidime/avibactam is recommended by international guidelines as the preferred treatment for KPC- and OXA-48-producing CRKP. Since its introduction in Taiwan in 2019, ceftazidime/avibactam-resistant strains have emerged. Our aim is to investigate the mechanisms of ceftazidime/avibactam resistance in CRKP in Taiwan and study their associated fitness costs.
Methods
Ceftazidime/avibactam-resistant CRKP strains with exposure to ceftazidime/avibactam isolated from clinical specimens were consecutively collected at Taipei Veterans General Hospital in 2020. The serial strains exhibiting ceftazidime/avibactam-susceptible and ceftazidime/avibactam-resistant phenotypes isolated from the same patient were characterized using whole-genome sequencing and tested for their growth rates and competitive abilities.
Results
A total of 35 ceftazidime/avibactam-resistant CRKP strains were identified, with 20 being metallo-β-lactamase producers. Ten strains harboured KPC variants, exhibiting MIC for ceftazidime/avibactam ranging from 64 to ≥256 mg/L. The 10 strains demonstrating high-level ceftazidime/avibactam resistance possessed mutated KPC variants: KPC-33 (n = 3), KPC-31 (n = 1), KPC-39 (n = 1), KPC-44 (n = 1), KPC-58 (n = 1), KPC-90 (n = 1), and two novel KPC variants. Ceftazidime/avibactam-resistant strains with KPC-33 and KPC-39 showed a significant fitness cost and lower growth rate compared to their parental strains. In contrast, ceftazidime/avibactam-resistant strains with KPC-58 and KPC-58 plus D179Y showed similar growth rates and competitive abilities compared to their parental strains.
Conclusions
Mutated KPC variants conferred high-level ceftazidime/avibactam resistance in Taiwan. Significant fitness costs were observed in both the ceftazidime/avibactam-resistant KPC-33 and KPC-39 strains. Despite conferring a similar level of ceftazidime/avibactam resistance, different KPC variants could entail varying degrees of fitness costs.
期刊介绍：
The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.
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