Clinical and Microbiological characteristics of patients with ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains
- PMID: 40251649
- PMCID: PMC12008838
- DOI: 10.1186/s12941-025-00797-5
Clinical and Microbiological characteristics of patients with ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains
Abstract
Background: Ceftazidime/avibactam (CZA)-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has emerged, typically due to mutations in the blaKPC gene. This study aimed to investigate the clinical and microbiological characteristics of patients with CZA-resistant KPC-producing K. pneumoniae, with a focus on comparing strains with KPC variants to those with wild-type KPC.
Methods: Unique adult patients with CZA-resistant KPC-producing K. pneumoniae were identified at Taipei Veterans General Hospital between February 2019 and June 2024. Clinical characteristics and outcomes were recorded, and KPC variants were detected using polymerase chain reaction followed by Sanger sequencing.
Results: A total of 60 cases of CZA-resistant KPC-producing K. pneumoniae were included. The 14-day and in-hospital mortality rates were 20% and 41.7%, respectively. Thirty-six strains (60%) harbored KPC variants, with 22 different types identified. KPC-33 (n = 12) was the most common variant. Previous isolation of carbapenem-resistant K. pneumoniae and prior exposure to CZA were more common in the KPC variant group than in the wild-type KPC group. Strains producing KPC variants showed a higher proportion of CZA minimum inhibitory concentration (MIC) ≥ 64 µg/mL (80.6% vs. 4.2%, p < 0.001) and restored meropenem susceptibility (MIC ≤ 4 µg/mL) (72.2% vs. 0%, p < 0.001) compared to those producing wild-type KPC. Additionally, the 14-day mortality rate was lower in patients infected with KPC variant strains compared to those with wild-type KPC strains (11.5% vs. 36.4%, p = 0.041).
Conclusion: CZA-resistant KPC-producing K. pneumoniae is associated with high mortality. Strains producing KPC variants are more likely to exhibit restored meropenem susceptibility and higher levels of CZA resistance.
Keywords: Ceftazidime/avibactam resistance; KPC variants; Klebsiella pneumoniae carbapenemase; Meropenem.
© 2025. The Author(s).
Conflict of interest statement
Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: This study was approved by the Institutional Review Board of Taipei Veterans General Hospital (2024-01-004BC) and informed consent was waived. Conflict of interest: The authors declare no competing interests.
References
-
- Yang X, Dong N, Chan EW, Zhang R, Chen S. Carbapenem resistance-encoding and virulence-encoding conjugative plasmids in Klebsiella pneumoniae. Trends Microbiol. 2021;29(1):65–83. 10.1016/j.tim.2020.04.012. - PubMed
-
- Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious diseases society of America 2024 guidance on the treatment of Antimicrobial-Resistant Gram-Negative infections. Clin Infect Dis. 2024;ciae403. 10.1093/cid/ciae403. - PubMed
-
- European Medicines Agency. Zavicefta: EPAR– Medicine Overview. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/zavicefta. Accessed 29 March 2025.
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