34. In vitro effect of ceftazidime/avibactam in combination with meropenem against carbapenem-resistant klebsiella pneumoniae

Nguyen Thi Van Anh, Nguyen Van Tan, Nguyen Gia Binh, Nguyen Hoang Anh, Vu Dinh Hoa, Nguyen Thi Cuc, Hoang Hai Linh, Pham Hong Nhung

Main Article Content

Abstract

This study evaluated the in vitro efficacy of a combination test consisting of ceftazidime/avibactam and meropenem against 198 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates using the checkerboard assay. Synergy activity was observed in 48.5% (96/198) of the isolates, while 51.5% (102/198) exhibited an indifferent response. Among the synergistic isolates, the MIC90 of ceftazidime/avibactam decreased by 8-fold, whereas MIC90 of meropenem decreased by 128-fold. In isolates with an indifferent interaction, ceftazidime/avibactam MIC90 still showed marked reductions (> 16-fold), while meropenem MIC remained largely unchanged. These findings suggest that the combination of ceftazidime/avibactam and meropenem may represent a promising therapeutic strategy for treating infections caused by carbapenem-resistant K. pneumoniae.

Article Details

References

1. Lin X chen, Li C li, Zhang S yang, Yang X feng, Jiang M. The Global and Regional Prevalence of Hospital-Acquired Carbapenem-Resistant Klebsiella pneumoniae Infection: A Systematic Review and Meta-analysis. Open Forum Infectious Diseases. 2024; 11(2): ofad649. doi:10.1093/ofid/ofad649.
2. World Health Organization. WHO Bacterial Priority Pathogens List, 2024: Bacterial Pathogens of Public Health Importance, to Guide Research, Development, and Strategies to Prevent and Control Antimicrobial Resistance. World Health Organization; 2024.
3. Logan LK, Weinstein RA. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. The Journal of Infectious Diseases. 2017; 215(suppl_1): S28-S36. doi:10.1093/infdis/jiw282.
4. Phạm Hồng Nhung, Nguyễn Tuấn Linh. Nhiễm trùng do các trực khuẩn Gram âm thường gặp tại Trung tâm Hồi sức tích cực, Bệnh viện Bạch Mai năm 2023. Tạp chí Nghiên cứu Y học. 2024; 178(5): 43-51. doi:10.52852/tcncyh.v178i5.2401.
5. Shields RK, Nguyen MH, Chen L, Press EG, Kreiswirth BN, Clancy CJ. Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections. Antimicrobial Agents and Chemotherapy. 2018; 62(5): 10.1128/aac.02497-17. doi:10.1128/aac.02497-17.
6. Shields RK, Chen L, Cheng S, et al. Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne blaKPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections. Antimicrobial Agents and Chemotherapy. 2017; 61(3): 10.1128/aac.02097-16. doi:10.1128/aac.02097-16.
7. Assefa GM, Roberts JA, Aslan AT, Mohammed SA, Sime FB. A systematic review and individual bacterial species level meta-analysis of in vitro studies on the efficacy of ceftazidime/avibactam combined with other antimicrobials against carbapenem-resistant Gram-negative bacteria. Journal of Antimicrobial Chemotherapy. 2025; 80(2): 334-346. doi:10.1093/jac/dkae451.
8. Kuai J, Zhang Y, Lu B, et al. In vitro Synergistic Activity of Ceftazidime-Avibactam in Combination with Aztreonam or Meropenem Against Clinical Enterobacterales Producing blaKPC or blaNDM. IDR. 2023; 16:3171-3182. doi:10.2147/IDR.S408228.
9. Wu Yun, Yu Wei, Chu Xiaobing, et al. Effect of ceftazidime-avibactam combined with different antimicrobials against carbapenem-resistant Klebsiella pneumoniae. Microbiology Spectrum. 2024; 12(6): e00107-24. doi:10.1128/spectrum.00107-24.
10. Zheng M, Li FH, Liu J, et al. Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae. Journal of Antimicrobial Chemotherapy. 2024; 79(5): 1069-1080. doi:10.1093/jac/dkae074.
11. Mikhail S, Singh NB, Kebriaei R, et al. Evaluation of the Synergy of Ceftazidime-Avibactam in Combination with Meropenem, Amikacin, Aztreonam, Colistin, or Fosfomycin against Well-Characterized Multidrug-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy. 2019; 63(8): 10.1128/aac.00779-19. doi:10.1128/aac.00779-19.
12. Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. CLSI document M07-A10. Published online 2015.
13. Clinical Microbiology Procedures Handbook. 4th edition. ASM Press Washington, DC; 2016.
14. Clinical and Laboratory Standards Institute, Wayne, PA. Performance Standards for Antimicrobial Susceptibility Testing. Vol CLSI supplement M100. 34th ed. Clinical and Laboratory Standards Institute; 2024.
15. Shen Z, Ding B, Ye M, et al. High ceftazidime hydrolysis activity and porin OmpK35 deficiency contribute to the decreased susceptibility to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae. Journal of Antimicrobial Chemotherapy. 2017; 72(7): 1930-1936. doi:10.1093/jac/dkx066.