Activity of novel β-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae: an in vitro study

doi:10.19871/j.cnki.xfcrbzz.2025.06.004

Abstract

Abstract: Objective To systematically elucidate the susceptibility profiles of carbapenem-resistant Klebsiella pneumoniae (CRKP) to novel β-lactamase inhibitor combinations through integrated bioinformatics analysis and in vitro antimicrobial susceptibility testing, thereby providing scientific evidence for optimizing clinical anti-infective treatment strategies. Method Performed broth micr-dilution assays to evaluate the susceptibility of 146 CRKP clinical isolates (collected from March to August 2023) to relebactam-, vaborbactam-, avibactam-, and taniborbactam-based combination regimens. Whole-genome sequencing was conducted, and molecular characteristics were analyzed using Kleborate. Phylogenetic reconstruction was performed using Snippy. Result Antimicrobial susceptibility testing demonstrated that β-lactam/β-lactamase inhibitor combinations (imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, aztreonam-avibactam, fcefepime-taniborbactam) exhibited significantly enhanced activity compared to monotherapies, with minimum inhibitory concentrations (MICs) decreased to 1/32 of the original value or lower, the susceptibility rates of all tested compound formulations exceeded 90%. Aztreonam-Avibactam (100%) and Fcefepime-Taniborbactam (99.3%) showed the highest efficacy. Molecular analysis revealed ST11 (84.2%) and KL64 (79.4%) as predominant sequence and capsular types, respectively. Carbapenem resistance was primarily mediated by bla_KPC-2 (90.4%), while high-frequency mutations in OmpK35 (91.8%) and OmpK36 (84.3%) also constituted the resistance mechanisms. Phylogenetic analysis indicated polyclonal transmission, with OXA-232-producing strains forming distinct clusters, suggesting potential adaptive advantages. Conclusion Novel β-lactamase inhibitor combinations demonstrated potent activity against CRKP isolates in our hospital. However, the emergence of resistant strains underscores the need for further investigation into resistance mechanisms and enhanced epidemiological surveillance.

Key words: Carbapenem-resistant Klebsiella pneumoniae, Novel β-lactamase inhibitors, In vitro antimicrobial susceptibility

CLC Number:

R378
R56

Ma Ke, Zhang Baofang, Xu Wei, Zhang Quan. Activity of novel β-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae: an in vitro study[J]. Electronic Journal of Emerging Infectious Diseases, 2025, 10(6): 24-31.

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