Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland.
Microb Drug Resist. 2019 Nov;25(9):1357-1364. doi: 10.1089/mdr.2018.0234. Epub 2019 Jul 11.
The aim of this study was to investigate the synergy between ceftazidime-avibactam, ertapenem, fosfomycin, and tigecycline against carbapenemase-producing using the test MIC:MIC (minimum inhibitory concentration) ratio synergy method. The results were interpreted using fractional inhibitory concentration index (FICI) to describe the effects of antimicrobial combinations . To assess the clinical significance of each antibiotic combination, the susceptible breakpoint index (SBPI) was calculated for each combination, and within each strain. The FICI method revealed that the most synergistic combinations against carbapenemase-producing were ceftazidime-avibactam with ertapenem and ceftazidime-avibactam with fosfomycin. This effect was demonstrated in 47% (9/19) of all tested clinical isolates. Considering the effects of all drug combinations in harboring , , and genes, we observed that the combination of ceftazidime-avibactam with fosfomycin was the most synergistic in New Delhi metallo-β-lactamase (NDM)-producing , and the combination of ceftazidime-avibactam with ertapenem was the most synergistic in carbapenemase (KPC)-producing . In addition, all tested combinations were synergistic against oxacillinase (OXA)-48-producing , except the combination of ceftazidime-avibactam with tigecycline. The SBPI index showed that ceftazidime-avibactam in combination with fosfomycin reduced the MIC to less than the susceptibility breakpoint among all tested carbapenemase-producing . Moreover, the combinations of ceftazidime-avibactam with ertapenem, and ceftazidime-avibactam with tigecycline were able to reduce the MIC to less than the susceptibility breakpoint in all KPC- and OXA-48-producing .
本研究旨在采用 MIC:MIC（最小抑菌浓度）比值协同试验，研究头孢他啶-阿维巴坦、厄他培南、磷霉素和替加环素对产碳青霉烯酶 的协同作用。采用抑菌浓度指数（FICI）来描述抗菌药物联合使用的效果，以解释结果。为评估每种抗生素联合应用的临床意义，计算了每种组合以及每个菌株的敏感断点指数（SBPI）。FICI 方法表明，对产碳青霉烯酶 最具协同作用的组合是头孢他啶-阿维巴坦与厄他培南和头孢他啶-阿维巴坦与磷霉素。这一作用在所有测试的临床 分离株中占 47%（9/19）。考虑到所有携带 、 和 基因的药物组合的作用，我们观察到头孢他啶-阿维巴坦与磷霉素的联合应用对新德里金属β-内酰胺酶（NDM）产生的 最具协同作用，头孢他啶-阿维巴坦与厄他培南的联合应用对产碳青霉烯酶（KPC）的 最具协同作用。此外，除了头孢他啶-阿维巴坦与替加环素的组合外，所有测试的组合对产 oxacillinase（OXA）-48的 均具有协同作用。SBPI 指数表明，头孢他啶-阿维巴坦与磷霉素的联合应用使所有测试的产碳青霉烯酶中，MIC 降低至药敏折点以下。此外，头孢他啶-阿维巴坦与厄他培南和头孢他啶-阿维巴坦与替加环素的联合应用，能够使所有产 KPC 和 OXA-48 的 MIC 降低至药敏折点以下。
