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 bla_KPC 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.