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Mechanisms and fitness of ceftazidime/avibactam-resistant Klebsiella pneumoniae clinical strains in Taiwan.
- Source :
-
International journal of antimicrobial agents [Int J Antimicrob Agents] 2024 Aug; Vol. 64 (2), pp. 107244. Date of Electronic Publication: 2024 Jun 24. - Publication Year :
- 2024
-
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.<br />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.<br />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.<br />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.<br /> (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)
- Subjects :
- Humans
Taiwan
Drug Resistance, Multiple, Bacterial genetics
Bacterial Proteins genetics
Bacterial Proteins metabolism
Carbapenem-Resistant Enterobacteriaceae drug effects
Carbapenem-Resistant Enterobacteriaceae genetics
Carbapenem-Resistant Enterobacteriaceae isolation & purification
Ceftazidime pharmacology
Klebsiella pneumoniae drug effects
Klebsiella pneumoniae genetics
Azabicyclo Compounds pharmacology
Drug Combinations
Anti-Bacterial Agents pharmacology
Klebsiella Infections microbiology
Klebsiella Infections drug therapy
Microbial Sensitivity Tests
beta-Lactamases genetics
beta-Lactamases metabolism
Whole Genome Sequencing
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7913
- Volume :
- 64
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of antimicrobial agents
- Publication Type :
- Academic Journal
- Accession number :
- 38925227
- Full Text :
- https://doi.org/10.1016/j.ijantimicag.2024.107244