黏菌素和多黏菌素B与美罗培南、利福平及替加环素的不同协同活性：对来自印度的耐碳青霉烯鲍曼不动杆菌的体外研究
Varied synergistic activity of colistin and polymyxin B with meropenem, rifampicin and tigecycline: An in vitro study on carbapenem resistant Acinetobacter baumannii from India.
作者信息
Tantry Manasa, Varma Muralidhar, Rao Shwethapriya, Mukhopadhyay Chiranjay, Eshwara Vandana Kalwaje
机构信息
Department of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India; Center for Antimicrobial Resistance and Education, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
出版信息
Indian J Med Microbiol. 2025 Jul-Aug;56:100889. doi: 10.1016/j.ijmmb.2025.100889. Epub 2025 May 31.
PURPOSE
Effective therapeutic choices for infections by carbapenem resistant Acinetobacter baumannii (CRAB) in resource constrained settings is limited. Prospective antimicrobial combinations with polymyxins, need to be tested for synergy to mitigate further development of resistance. This study evaluates the synergistic effects of colistin and polymyxin B combined with meropenem, rifampicin, and tigecycline against CRAB isolates from bloodstream infections.
METHODS
Twenty-five epidemiologically distinct CRAB strains were included. The minimum inhibitory concentrations (MICs) of the antimicrobials were determined by broth microdilution. The synergistic activities of the antimicrobial combinations were evaluated by checkerboard broth microdilution (CBM). Antimicrobials were tested at concentrations from 4 to 8 times down to 1/8-1/16 of their expected MIC, with a final inoculum of 10 CFU/mL. The antimicrobial combinations that demonstrated greater synergistic activity were confirmed using the time-kill assay (TKA).
RESULTS
None of the strains were resistant to polymyxins (MIC ≤4 mg/L). Colistin-meropenem, colistin-rifampicin and colistin-tigecycline combinations achieved superior synergy over the polymyxin B-meropenem, polymyxin B-rifampicin and polymyxin B-tigecycline combinations (P=<0.001, P = 0.03, and P = 0.01, respectively) in the CBM assay. In the TKA, combinations of colistin (0.1-0.5 mg/L) with subinhibitory concentrations of meropenem (4-8 mg/L), rifampicin (1-4 mg/L), and tigecycline (0.06-0.25 mg/L) exhibited synergistic and bactericidal activity against a subset of isolates at 24 h.
CONCLUSIONS
Significant concordance between the CBM and TKA was observed. Our findings suggest that subinhibitory antimicrobial concentrations in combinations can improve therapeutic efficacy and minimize polymyxin side effects. Additionally, in vivo studies are warranted to optimize the combinational therapy.
目的
在资源有限的环境中，针对耐碳青霉烯类鲍曼不动杆菌（CRAB）感染的有效治疗选择有限。与多粘菌素的前瞻性抗菌联合用药，需要进行协同作用测试，以减轻耐药性的进一步发展。本研究评估了黏菌素和多粘菌素B与美罗培南、利福平及替加环素联合使用对血流感染中分离出的CRAB菌株的协同作用。
方法
纳入25株流行病学特征不同的CRAB菌株。采用肉汤微量稀释法测定抗菌药物的最低抑菌浓度（MIC）。通过棋盘微量稀释法（CBM）评估抗菌药物联合使用的协同活性。抗菌药物的测试浓度范围为预期MIC的4至8倍直至1/8 - 1/16，最终接种量为10 CFU/mL。使用时间杀菌试验（TKA）对表现出更强协同活性的抗菌药物联合进行确认。
结果
所有菌株对多粘菌素均不耐药（MIC≤4 mg/L）。在CBM试验中，黏菌素 - 美罗培南、黏菌素 - 利福平及黏菌素 - 替加环素联合用药比多粘菌素B - 美罗培南、多粘菌素B - 利福平及多粘菌素B - 替加环素联合用药具有更强的协同作用（P<0.001、P = 0.03及P = 0.01）。在TKA试验中，黏菌素（0.1 - 0.5 mg/L）与亚抑菌浓度的美罗培南（4 - 8 mg/L）、利福平（1 - 4 mg/L）及替加环素（0.06 - 0.25 mg/L）联合使用在24小时时对部分分离菌株表现出协同和杀菌活性。
结论
观察到CBM和TKA之间存在显著一致性。我们的研究结果表明，联合使用亚抑菌浓度的抗菌药物可提高治疗效果并使多粘菌素的副作用最小化。此外，有必要进行体内研究以优化联合治疗方案。
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