International Health Management Associates, Inc., Schaumburg, IL, US.
Drug Discovery & Disease Research Laboratory, Shionogi & Co., Ltd., Osaka, Japan.
Int J Antimicrob Agents. 2019 Feb;53(2):177-184. doi: 10.1016/j.ijantimicag.2018.10.007. Epub 2018 Oct 26.
Cefiderocol is a siderophore cephalosporin in development for treatment of infections caused by Gram-negative bacilli, including carbapenem-resistant and multidrug-resistant isolates. β-Lactamase carriage and in vitro activity of cefiderocol were determined against 1272 meropenem-non-susceptible isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii collected as part of the SIDERO-WT-2014 surveillance study. Minimum inhibitory concentration (MIC) values for cefiderocol were ≤4 µg/mL against 97.7% of tested isolates, including 100% of IMP-positive (range, 1-2 µg/mL), OXA-58-positive (MIC, 1 µg/mL), KPC-positive (MIC, 2 µg/mL), VIM-positive (MIC, 2 µg/mL), and OXA-48-like-positive (MIC, 4 µg/mL) isolates; 99.3% of carbapenemase-negative isolates (MIC, 1 µg/mL); 97.2% of OXA-23-positive isolates (MIC, 1 µg/mL); 95.2% of OXA-24-positive isolates (MIC, 1 µg/mL); 91.7% of GES-positive isolates (MIC, 4 µg/mL); and 64.3% of NDM-positive isolates (MIC, 8 µg/mL). A total of 29 isolates (2.3%; 15 OXA-23-producers, 6 OXA-24-producers, 5 NDM-producers, and 3 carbapenemase-negative isolates) exhibited cefiderocol MIC ≥8 µg/mL, confirming there was no clear correlation between carriage of β-lactamases included in the molecular testing algorithm and elevated cefiderocol MICs. Similarly, no correlation was observed between cefiderocol MICs and truncation or loss of porin proteins in meropenem-non-susceptible isolates of E. coli and K. pneumoniae. Cefiderocol MICs were also ≤4 µg/mL against 99.3% of 136 colistin-resistant Enterobacteriaceae collected as part of the SIDERO-WT-2014 study, including isolates carrying mcr-1 (MIC, 2 µg/mL). Cefiderocol demonstrated potent in vitro activity against a collection of carbapenemase-producing and carbapenemase-negative meropenem-non-susceptible Gram-negative bacilli for which few treatment options are available, including the majority of metallo-β-lactamase producing isolates identified.
头孢他啶罗是一种新型的铁载体头孢菌素，目前正处于研发阶段，用于治疗由革兰氏阴性菌引起的感染，包括耐碳青霉烯类和多重耐药的分离株。本研究通过对 2014 年 SIDERO-WT 监测研究中收集的 1272 株耐美罗培南的肠杆菌科、铜绿假单胞菌和鲍曼不动杆菌进行β-内酰胺酶携带情况和头孢他啶罗的体外活性检测，结果表明：头孢他啶罗对 97.7%的受试分离株的最低抑菌浓度（MIC）值≤4μg/ml，包括 100%的 IMP 阳性（范围 1-2μg/ml）、OXA-58 阳性（MIC=1μg/ml）、KPC 阳性（MIC=2μg/ml）、VIM 阳性（MIC=2μg/ml）和 OXA-48 样阳性（MIC=4μg/ml）分离株；99.3%的碳青霉烯酶阴性分离株（MIC=1μg/ml）；97.2%的 OXA-23 阳性分离株（MIC=1μg/ml）；95.2%的 OXA-24 阳性分离株（MIC=1μg/ml）；91.7%的 GES 阳性分离株（MIC=4μg/ml）；64.3%的 NDM 阳性分离株（MIC=8μg/ml）。共有 29 株（2.3%；15 株 OXA-23 产酶株、6 株 OXA-24 产酶株、5 株 NDM 产酶株和 3 株碳青霉烯酶阴性分离株）对头孢他啶罗的 MIC 值≥8μg/ml，证实了在分子检测算法中检测到的β-内酰胺酶的携带情况与头孢他啶罗 MIC 值升高之间没有明显的相关性。同样，在耐美罗培南的大肠埃希菌和肺炎克雷伯菌分离株中，也未观察到头孢他啶罗 MIC 值与孔蛋白截断或缺失之间存在相关性。头孢他啶罗对 SIDERO-WT 2014 研究中收集的 136 株多粘菌素耐药肠杆菌科的 MIC 值也≤4μg/ml，包括携带 mcr-1 的分离株（MIC=2μg/ml）。头孢他啶罗对产碳青霉烯酶和碳青霉烯酶阴性的耐美罗培南革兰氏阴性杆菌具有很强的体外活性，这些菌对治疗方法的选择有限，包括大多数鉴定出的金属β-内酰胺酶产生菌。
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