Novel KPC-2 variants and epidemic ST463 clones underlie ceftazidime/avibactam resistance in carbapenem-resistant Pseudomonas aeruginosa

Sep 29, 2026

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Carbapenem-resistant Pseudomonas aeruginosa (CRPA) creates a major treatment challenge because effective options are limited. Ceftazidime–avibactam (CZA) is a last-resort drug, yet resistance is increasingly reported, especially via blaKPC variants. Using 273 CRPA isolates from two Hangzhou tertiary hospitals (2021–2022), CZA resistance was found in 13.9% and was linked to ST463, blaKPC diversification, and virulence genes. Three new blaKPC variants—KPC-14, KPC-33, and KPC-86—conferred high-level CZA resistance, with KPC-86 on a mobile element and evidence of within-patient evolution. These findings indicate an urgent need for genomic surveillance and stewardship.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Abstract

Study design and resistance prevalence

Genomic findings and identified blaKPC variants

Clinical implications and need for surveillance

| Clinical Microbiology | Research Article Novel KPC-2 variants and epidemic ST463 clones underlie ceftazidime/avibactam resistance in carbapenem-resistant Pseudomonas aeruginosa Yanyan Hu,1 Qiaoling Sun,2 Weiyi Shen,1 Jingjing Du,1 Zeng Kaiqi,1 Rong Zhang1 AUTHOR AFFILIATIONS See affiliation list on p. 12. ABSTRACT Carbapenem-resistant Pseudomonas aeruginosa (CRPA) presents a serious clinical challenge due to limited treatment options. Ceftazidime–avibactam (CZA) is a critical last-resort agent against multidrug-resistant Gram-negative pathogens; however, resistance is emerging, particularly mediated by blaKPC variants. In this study, we investigated the prevalence and mechanisms of CZA resistance among CRPA isolates collected from two tertiary hospitals in Hangzhou between 2021 and 2022. A total of 273 non-duplicate CRPA isolates were screened, among which 13.9%(38/273) exhibited CZA resistance (MIC ≥ 16 µg/mL) . Whole-genome sequencing revealed that resistant strains were highly resistant to carbapenems, cephalosporins, and aztreonam but retained partial susceptibility to aminoglycosides and polymyxins. ST463 was the predominant sequence type (76.3%), strongly associated with blaKPC-2 carriage and virulence genes, such as exoU and pldA. Notably, three blaKPC variants—KPC-14, KPC-33, and KPC-86—were identified, all conferring high-level resistance to CZA (MIC > 32 µg/mL) . KPC-86 was discovered for the first time in P. aeruginosa, embedded in an IS26-flanked transposon, suggesting potential for horizontal transfer. Sequential recovery of KPC-86 and KPC-33 from the same patient supports in vivo evolution under antibiotic pressure. These findings highlight the evolving threat of CZA resistance in CRPA, driven by blaKPC diversification within high-risk clones. Continued genomic surveillance and antimicrobial stewardship are urgently needed to preserve the efficacy of CZA. IMPORTANCE Ceftazidime–avibactam (CZA) is one of the few remaining options to treat serious infections caused by drug-resistant Pseudomonas aeruginosa. However, its effectiveness is now being threatened by emerging genetic changes that reduce susceptibility. In this study, we investigated CZA-resistant strains and uncovered three variants of the resistance gene blaKPC, including one—KPC-86—never before seen in P. aeruginosa. This variant was located on a mobile genetic element, raising concerns about its potential to spread between bacteria. We also documented the evolution of resistance within a single patient, showing how treatment pressure can drive genetic change. By combining clinical, microbiological, and genomic data, our findings highlight an urgent need for ongoing surveillance and careful antibiotic use to preserve the usefulness of last-resort drugs like CZA. This work informs both clinicians and public health experts onemerging resistance threats. KEYWORDS carbapenem-resistant Pseudomonas aeruginosa, sequence typing 463, KPC-2 variants, ceftazidime/avibactam P seudomonas aeruginosa is a prominent opportunistic pathogen and a leading cause of nosocomial infections, particularly among immunocompromised patients. These infections, including pneumonia and bloodstream infections, can be severe and are Editor Krisztina M. Papp-Wallace, JMI Laboratories, North Liberty, Iowa, USA Address correspondence to Rong Zhang, zhang[rong@zju.edu.cn](rong@zju.edu.cn). authors declare conflict of interest associated with high morbidity and mortality rates, especially when caused by multidrug-resistant strains (1) . Treatment of nosocomial infections due to multidrugresistant P. aeruginosa presents significant challenges, primarily due to the limited availability of effective antimicrobial agents (2, 3) . Carbapenems have traditionally been considered the cornerstone of therapy for severe infections caused by P. aeruginosa; however, the emergence of carbapenem-resistant P. aeruginosa (CRPA) has considerably complicated treatment options (4, 5) . T

FAQs

What problem does the study address regarding CRPA treatment?

The study addresses emerging resistance to ceftazidime–avibactam (CZA) in carbapenem-resistant Pseudomonas aeruginosa, which threatens one of the remaining last-resort treatment options.

How many CRPA isolates were analyzed and what proportion showed CZA resistance?

A total of 273 non-duplicate CRPA isolates were screened, and 13.9% (38/273) exhibited CZA resistance.

Which sequence type and resistance gene variants were strongly associated with CZA resistance?

ST463 was the predominant sequence type (76.3%) and was strongly associated with blaKPC-2 carriage and virulence genes. Three blaKPC variants—KPC-14, KPC-33, and KPC-86—were identified, all linked to high-level CZA resistance, including the first report of KPC-86 in P. aeruginosa.

Sep 29, 2026

Uploaded by Aldword