Yang Feng, Yang Yang, Wu Shi, Tang Chengkang, Yin Dandan, Guo Yan, Zhu Demei, Hu Fupin
Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai, 200040, China.
Eur J Clin Microbiol Infect Dis. 2025 Aug 12. doi: 10.1007/s10096-025-05232-3.
Carbapenem-resistant organisms pose a significant public health threat due to high mortality and limited treatment options. This study aimed to evaluate the in vitro antimicrobial activity of the novel β-lactamase inhibitor FL058 combined with meropenem against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa clinical isolates.
The MICs of 85 clinical isolates, including KPC- or NDM-producing Enterobacterales and carbapenem-resistant/susceptible P. aeruginosa, were determined using broth microdilution. Additionally, bactericidal activity, effects of culture conditions, post-antibiotic effect, and post-β-lactamase inhibitory effect of meropenem-FL058 were evaluated. Ceftazidime-avibactam served as comparator.
Meropenem-FL058 showed potent activity against KPC-producing Enterobacterales (100% susceptibility, MIC ≤ 0.25 mg/L, most MBC/MIC ratios = 1) and moderate activity against NDM-producing Enterobacterales (> 58% susceptibility, MIC ≤ 0.06 mg/L for E. coli, 8 mg/L for Klebsiella pneumoniae, and 64 mg/L for other carbapenem-resistant Enterobacterales, most MBC/MIC ratios = 2). Of note, NDM-producing E. coli achieved a susceptibility of 91.7%. Meropenem-FL058 showed susceptibility rates of 73.9% for NDM-1 and 62.5% for NDM-5-producing strains. Activity against carbapenem-resistant P. aeruginosa was limited (18.2% susceptibility, MIC = 16 mg/L, MBC/MIC ratio = 8). Inoculum density and culture medium pH significantly affected the antimicrobial activity, while serum and metal ions had minimal effects. No significant post-antibiotic effect or post-β-lactamase inhibitory effect was observed.
Meropenem-FL058 showed promising in vitro activity against KPC-producing Enterobacterales and some NDM-1/5-producing strains. However, its limited efficacy against certain NDM-producers and carbapenem-resistant P. aeruginosa highlights the variability in activity across different resistance mechanisms, suggesting the potential need for combination strategies in clinical settings.
耐碳青霉烯类微生物因其高死亡率和有限的治疗选择而对公共卫生构成重大威胁。本研究旨在评估新型β-内酰胺酶抑制剂FL058与美罗培南联合使用对耐碳青霉烯类肠杆菌科细菌和铜绿假单胞菌临床分离株的体外抗菌活性。
采用肉汤微量稀释法测定85株临床分离株的最低抑菌浓度（MIC），包括产KPC或NDM的肠杆菌科细菌以及耐碳青霉烯类/敏感的铜绿假单胞菌。此外，还评估了美罗培南-FL058的杀菌活性、培养条件的影响、抗生素后效应以及β-内酰胺酶抑制后效应。头孢他啶-阿维巴坦作为对照。
美罗培南-FL058对产KPC的肠杆菌科细菌显示出强效活性（100%敏感，MIC≤0.25mg/L，大多数MBC/MIC比值=1），对产NDM的肠杆菌科细菌显示出中等活性（>58%敏感，大肠杆菌MIC≤0.06mg/L，肺炎克雷伯菌MIC≤8mg/L，其他耐碳青霉烯类肠杆菌科细菌MIC≤64mg/L，大多数MBC/MIC比值=2）。值得注意的是，产NDM的大肠杆菌敏感性达到91.7%。美罗培南-FL058对产NDM-1菌株的敏感率为73.9%，对产NDM-5菌株的敏感率为62.5%。对耐碳青霉烯类铜绿假单胞菌的活性有限（18.2%敏感，MIC=16mg/L，MBC/MIC比值=8）。接种物密度和培养基pH值显著影响抗菌活性，而血清和金属离子的影响最小。未观察到明显的抗生素后效应或β-内酰胺酶抑制后效应。
美罗培南-FL058对产KPC的肠杆菌科细菌和一些产NDM-1/5的菌株显示出有前景的体外活性。然而，其对某些产NDM菌株和耐碳青霉烯类铜绿假单胞菌的疗效有限，凸显了不同耐药机制间活性的差异，提示临床环境中可能需要联合策略。
