The aim of this study is to investigate the combination of cefepime and sulbactam. Sulbactam, when administered , will effectively inhibit all Extended-spectrum beta lactamases (ESBLs) of the microorganism, while cefepime will inhibit the growth of the resistant microorganisms since it will not be hydrolyzed by OXA-48. Forty OXA-48-producing K. pneumoniae strains were investigated for their Minimum inhibitory concentrations (MICs) for carbapenems, cefepime, and cefepime + sulbactam by broth microdilution method. Also, the mutant prevention concentration (MPC)s of cefepime alone or in combination with sulbactam was determined. Additionally, the bactericidal activities of cefepime and cefepime + sulbactam were evaluated by the time-kill curve (TKC) assay against selected strains. Also, the in vitro synergistic activity of cefepime + sulbactam combination was determined by TKC. Based on MIC results, up to 35/40 and 34/40 of the strains were resistant to carbapenems and cefepime, respectively. Cefepime + sulbactam MIC range was lower than those for cefepime alone against all the studied isolates. Moreover, cefepime + sulbactam combination presented lower MPC values than cefepime alone. The synergistic interactions of cefepime + sulbactam were also achieved against studied strains at 24 h. No antagonism was observed against studied K. pneumoniae strains. The findings of this study displayed that cefepime + sulbactam combination had synergistic or additive effect against OXA-48-producing K. pneumoniae strains. Additionally, it was first observed that this combination could display a lower MPC than cefepime alone. Further investigations may be helpful for understanding the effectiveness of cefepime + sulbactam combinations for OXA-48-positive carbapenem-resistant K. pneumoniae isolates.

中文翻译：

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单独或与舒巴坦联合使用头孢吡肟对 OXA-48 阳性肺炎克雷伯菌分离株的体外协同作用和突变预防浓度

本研究的目的是研究头孢吡肟和舒巴坦的组合。使用舒巴坦时，将有效抑制微生物的所有超广谱 β 内酰胺酶 (ESBL)，而头孢吡肟将抑制耐药微生物的生长，因为它不会被 OXA-48 水解。通过肉汤微量稀释法研究了 40 株产 OXA-48 肺炎克雷伯菌菌株对碳青霉烯、头孢吡肟和头孢吡肟 + 舒巴坦的最低抑菌浓度 (MIC)。此外，还测定了单独使用头孢吡肟或与舒巴坦联合使用时的突变预防浓度 (MPC)。此外，头孢吡肟和头孢吡肟 + 舒巴坦的杀菌活性通过对选定菌株的时间-杀伤曲线 (TKC) 测定进行评估。还，通过TKC测定头孢吡肟+舒巴坦组合的体外协同活性。根据 MIC 结果，高达 35/40 和 34/40 的菌株分别对碳青霉烯类和头孢吡肟具有抗性。头孢吡肟 + 舒巴坦 MIC 范围低于单独使用头孢吡肟对所有研究的分离株的 MIC 范围。此外，头孢吡肟 + 舒巴坦组合的 MPC 值低于单独的头孢吡肟。头孢吡肟 + 舒巴坦在 24 小时后对所研究的菌株也实现了协同相互作用。没有观察到对所研究的肺炎克雷伯菌菌株的拮抗作用。这项研究的结果表明，头孢吡肟 + 舒巴坦组合对产 OXA-48 的肺炎克雷伯菌菌株具有协同或相加作用。此外，首次观察到这种组合比单独使用头孢吡肟显示出更低的 MPC。