Yao Huijuan, Liu Jingxian, Jiang Xueyan, Chen Feng, Lu Xiaotong, Zhang Jian
Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Clinical Laboratory, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Infect Drug Resist. 2021 Jan 12;14:79-87. doi: 10.2147/IDR.S282386. eCollection 2021.
To evaluate the in-vitro antibacterial activity of drug combinations against carbapenem-resistant (CRKP) and to explore the guiding significance of the combined drug susceptibility results for determining the clinical efficacy in patients with CRKP infection.
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.
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.
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.
评估联合用药对耐碳青霉烯类肺炎克雷伯菌(CRKP)的体外抗菌活性,并探讨联合药敏结果对CRKP感染患者临床疗效判定的指导意义。
采用 Kirby-Bauer 纸片扩散法进行药敏试验。收集 CRKP 感染患者的临床资料及样本培养的药敏结果,并进行回顾性分析。
16 例 CRKP 患者均有基础疾病,其中血流感染最为常见。入住重症监护病房史、侵入性操作史及营养状况差被记录为高危因素。体外药敏结果显示,CRKP 对替加环素、多黏菌素和头孢他啶/阿维巴坦的敏感率分别为 100%、75.0%和 66.7%。在两药联合中,多黏菌素+替加环素、头孢他啶阿维巴坦+替加环素或(氨曲南、多黏菌素 B、磷霉素)、磷霉素+多黏菌素、亚胺培南+替加环素及磷霉素+替加环素的协同和/或累积抗菌效应分别为 100%、87.5%(81.3%、75.0%、75.0%)、68.8%、68.8%和 62.5%。三药联合如亚胺培南+替加环素+多黏菌素、亚胺培南+磷霉素+替加环素、亚胺培南+磷霉素+多黏菌素及头孢他啶阿维巴坦+多黏菌素+磷霉素的协同效应分别为 75.0%、68.8%、62.5%和 62.5%。临床疗效结果显示,亚胺培南+替加环素+磷霉素联合用药效果最佳,其次为美罗培南+磷霉素、亚胺培南+替加环素、头孢他啶阿维巴坦及头孢他啶+阿米卡星。
联合药敏结果有助于指导 CRKP 感染患者抗菌药物治疗方案的调整。为控制 CRKP 感染,发现碳青霉烯类药物或头孢他啶阿维巴坦与替加环素和/或磷霉素和/或多黏菌素 B 联合使用时抗菌活性更佳。