Effectiveness of antimicrobial agent combinations against carbapenem-producing Klebsiella pneumoniae with KPC variants in China

作者：Congcong Liu, Yuchen Wu, Yanyan Zhang, Zelin Yan, Danxia Gu, Hongwei Zhou, Ning Dong, Chang Cai, Gongxiang Chen, Rong Zhang · 发表于：Frontiers in Microbiology · 年份：2025 · DOI：10.3389/fmicb.2024.1519319 · 被引用次数：6 · 研究领域：Antibiotic Resistance in Bacteria、Antibiotics Pharmacokinetics and Efficacy、Antibiotic Use and Resistance

Purpose Carbapenem-resistant Klebsiella pneumoniae (CRKP) producing carbapenemases poses a global threat to public health. Antimicrobial agent combinations have been promoted as a potential therapeutic strategy for infections. The most effective antimicrobial combinations against CRKP strains producing different carbapenemases are currently unclear, particularly those producing the KPC variant carbapenemases. This study is aimed to evaluate the effectiveness of various antimicrobial agent combinations against CRKP strains with different carbapenemases. Methods A checkerboard assay involving 24 antimicrobial agent combinations was conducted on 44 strains of carbapenemase-producing CRKP isolated from patients of which 13 CRKP strains carried single KPC variants. The 24 antimicrobial combinations were based on meropenem, polymyxin, tigecycline, ceftazidime/avibactam, respectively. The fractional inhibitory concentration (FIC) indexes were calculated for each combination of antimicrobial agents. Results The distribution of carbapenemases in 44 CRKP strains was as follows: KPC variants ( n = 13, 29.5%), KPC-2 ( n = 10, 22.7%), metallo- β -lactamases ( n = 9, 20.5%), OXA-48-like ( n = 12, 27.3%). In the checkerboard assay, the combination of polymyxin and aztreonam exhibited the highest synergistic effect against CRKP strains, with a rate of 95.5% (42/44). This was followed by polymyxin-meropenem at 88.6% (39/44) and polymyxin-levofloxacin at 68.2% (30/44). Additionally, polymyxin-...