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Mechanisms and fitness of ceftazidime/avibactam-resistant Klebsiella pneumoniae clinical strains in Taiwan.

Author information

Affiliations

  • 1. Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
      Authors
    • Chou SH 1
    (1 author)
  • 2. Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
      Authors
    • Chuang C 2
    • Juan CH 2
    • Lin YT 2
    (3 authors)
  • 3. Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
      Authors
    • Ho YC 3
    • Liu SY 3
    (2 authors)
  • 4. Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY.
      Authors
    • Chen L 4
    (1 author)

ORCIDs linked to this article

International Journal of Antimicrobial Agents, 24 Jun 2024, 64(2):107244
https://doi.org/10.1016/j.ijantimicag.2024.107244 PMID: 38925227 

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.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.ijantimicag.2024.107244

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