International journal of antimicrobial agents · 2026
Ceftazidime/avibactam-resistant carbapenem-resistant Klebsiella pneumoniae in China: A nationwide multicenter study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Lu Rongqi, Wu Yun, Ma Ruirui, Feng Rongxiang, Qin Binrong, Zhou Xinyi, Kang Wei, Zhang Ge, Li Jin, Wang Tong, Xu Yingchun, Liu Yali
Аннотация
OBJECTIVE: To define the epidemiology, antimicrobial resistance phenotypes, and genomic mechanisms of ceftazidime/avibactam (CZA) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) across China.
METHODS: We conducted a multicentre surveillance (2021-2024) across 26 tertiary hospitals in 19 provinces. Isolates underwent identification, broth microdilution antimicrobial susceptibility testing, and whole-genome sequencing with genomic analyses. In KPC-2-only CZA-resistant isolates, blaKPC-2 expression and copy number were quantified, and porin/efflux mutations and expression were evaluated.
RESULTS: Among 4739 isolates, 101 (2.1%) were CZA-resistant CRKP, mainly in older male inpatients with lower respiratory infections. NDM alone predominated (55.4%); dual NDM+KPC producers showed the broadest, highest-level resistance. Tigecycline remained the most active (3%), while resistance to other agents was generally ≥37%. Genomic analysis revealed substantial resistance burdens (mean 15.4 antibiotic resistance genes; 4.1 plasmids per isolate), with ST11 predominating (42.6%) and concentrated in a major cluster linked to KL64/KL47 and IncF replicons; hypervirulence markers were absent. Among nine (8.9%) KPC-2-only CZA-resistant isolates, high-MIC strains showed significantly higher blaKPC-2 expression and copy number; susceptibility was restored in 8 of 9 isolates with 8 mg/L avibactam. Stepwise induction demonstrated increasing blaKPC-2 expression with rising MICs. In addition, 8 of 9 isolates carried OmpK35/OmpK36 and/or AcrA/B alterations, and efflux inhibition with phenylalanine-arginine-naphthylamide reduced MICs by more than fourfold in 6 of 9 isolates.
CONCLUSIONS: CZA-resistant CRKP in China are uncommon but widely distributed, driven mainly by epidemic ST11-KL64/KL47 lineages with extensive multidrug resistance and no convergence with classical hypervirulence. In the small subset of KPC-2-only isolates, resistance correlated with increased blaKPC-2 expression/copy number and efflux involvement, with frequent co-occurrence of porin structural variants.
METHODS: We conducted a multicentre surveillance (2021-2024) across 26 tertiary hospitals in 19 provinces. Isolates underwent identification, broth microdilution antimicrobial susceptibility testing, and whole-genome sequencing with genomic analyses. In KPC-2-only CZA-resistant isolates, blaKPC-2 expression and copy number were quantified, and porin/efflux mutations and expression were evaluated.
RESULTS: Among 4739 isolates, 101 (2.1%) were CZA-resistant CRKP, mainly in older male inpatients with lower respiratory infections. NDM alone predominated (55.4%); dual NDM+KPC producers showed the broadest, highest-level resistance. Tigecycline remained the most active (3%), while resistance to other agents was generally ≥37%. Genomic analysis revealed substantial resistance burdens (mean 15.4 antibiotic resistance genes; 4.1 plasmids per isolate), with ST11 predominating (42.6%) and concentrated in a major cluster linked to KL64/KL47 and IncF replicons; hypervirulence markers were absent. Among nine (8.9%) KPC-2-only CZA-resistant isolates, high-MIC strains showed significantly higher blaKPC-2 expression and copy number; susceptibility was restored in 8 of 9 isolates with 8 mg/L avibactam. Stepwise induction demonstrated increasing blaKPC-2 expression with rising MICs. In addition, 8 of 9 isolates carried OmpK35/OmpK36 and/or AcrA/B alterations, and efflux inhibition with phenylalanine-arginine-naphthylamide reduced MICs by more than fourfold in 6 of 9 isolates.
CONCLUSIONS: CZA-resistant CRKP in China are uncommon but widely distributed, driven mainly by epidemic ST11-KL64/KL47 lineages with extensive multidrug resistance and no convergence with classical hypervirulence. In the small subset of KPC-2-only isolates, resistance correlated with increased blaKPC-2 expression/copy number and efflux involvement, with frequent co-occurrence of porin structural variants.
Предметные рубрики MeSH
CeftazidimeChinaHumansAzabicyclo CompoundsKlebsiella pneumoniaeMicrobial Sensitivity TestsAnti-Bacterial AgentsKlebsiella InfectionsDrug CombinationsMaleDrug Resistance, Multiple, Bacterialbeta-LactamasesWhole Genome SequencingThird Generation CephalosporinsFemaleCarbapenem-Resistant EnterobacteriaceaeCarbapenemsPorins