Analysis of the Clinical Effect of Combined Drug Susceptibility to Guide Medication for Carbapenem-Resistant Klebsiella pneumoniae Patients Based on the Kirby–Bauer Disk Diffusion Method

Abstract

Objective To evaluate the in-vitro antibacterial activity of drug combinations against carbapenem-resistant Klebsiella pneumoniae (CRKP) and to explore the guiding significance of the combined drug susceptibility results for determining the clinical efficacy in patients with CRKP infection. Methods Antimicrobial susceptibility testing was performed using the Kirby–Bauer disk diffusion method. The clinical data of CRKP-infected patients and the drug susceptibility results of sample cultures were gathered and retrospectively analyzed. Results All 16 CRKP patients had underlying diseases, of which the bloodstream infection was the most common one. Intensive care unit admission history, invasive operation history, and poor nutritional status were recorded to be the high-risk factors. The in-vitro drug susceptibility results indicated that CRKP exhibited 100%, 75.0%, and 66.7% susceptibilities to tigecycline, polymyxin, and ceftazidime/avibatan, respectively. In case of two-drug combinations, polymyxin+tigecycline, ceftazidime avibatan+tigecycline or (aztreonam, polymyxin B, fosfomycin), fosfomycin+polymycin, imipenem+tigecycline, and fosfomycin+tigecycline exhibited 100%, 87.5% (81.3%, 75.0%, 75.0%), 68.8%, 68.8%, and 62.5%, respectively, synergistic and/or cumulative antibacterial effects. Three-drug combinations such as imipene+tigecycline+polymyxin, imipenem+fosfomycin+tigecycline, imipenem+fosfomycin+polymyxin, and ceftazidime avibatan+polymyxin+fosfomycin demonstrated 75.0%, 68.8%, 62.5%, and 62.5% synergistic effects, respectively. The clinical efficacy results revealed that the combination of imipenem+tigecycline+fosfomycin showed the best results, followed by meropenem+fosfomycin, imipenem+tigecycline, ceftazidime avibatan, and ceftazidime+amikacin. Conclusion The combined drug susceptibility results can facilitate guidance of the adjustment of antibacterial drug treatment regimens in patients with CRKP infection. For controlling the CRKP infection, it was found that treatment with carbapenems or ceftazidime avibatan demonstrated better antibacterial activity when combined with tigecycline and/or fosfomycin and/or polymyxin B.