JMI Laboratories, North Liberty, IA, USA.
J Antimicrob Chemother. 2022 Sep 30;77(10):2642-2649. doi: 10.1093/jac/dkac233.
Zidebactam, a bicyclo-acyl hydrazide β-lactam 'enhancer' antibiotic, in combination with cefepime (WCK 5222) is under clinical development for the treatment of resistant Gram-negative infections.
To evaluate the in vitro activity of cefepime/zidebactam and comparators against 24 220 Gram-negative bacteria.
Organisms were consecutively collected in 2018-19 from 137 medical centres located in the USA (n = 9140), Western Europe (W-EU; n = 5929), Eastern Europe (E-EU; n = 3036), the Asia-Pacific region (APAC; n = 3791) and Latin America (LATAM; n = 2324). The isolates were susceptibility tested using the broth microdilution method as part of the SENTRY Program. Cefepime/zidebactam was tested at a 1:1 ratio.
Cefepime/zidebactam was highly active against Enterobacterales (MIC50/90 0.03/0.25 mg/L; 99.9% inhibited at ≤8 mg/L) and retained potent activity against carbapenem-resistant Enterobacterales (CRE) isolates (97.8% inhibited at ≤8 mg/L). CRE rates varied widely from 1.1% in the USA to 1.9% in W-EU, 3.6% in APAC and 14.6% in E-EU (3.9% overall). The most common carbapenemase genes observed overall were blaKPC (37.6% of CRE), blaOXA-48-like (30.0%) and blaNDM (23.8%). Resistance to ceftazidime/avibactam among CRE was elevated in APAC (64.8%), E-EU (25.5%) and LATAM (20.7%). Against Pseudomonas aeruginosa, cefepime/zidebactam inhibited 99.2% of isolates at ≤8 mg/L and susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam was lowest in E-EU (83.9% and 82.0%, respectively). Cefepime/zidebactam exhibited good activity against Stenotrophomonas maltophilia (80.0% inhibited at ≤8 mg/L) and Burkholderia cepacia (89.4% inhibited at ≤8 mg/L).
Cefepime/zidebactam demonstrated potent in vitro activity against a large worldwide collection of contemporary clinical isolates of Gram-negative bacteria.
齐他培南是一种双环酰肼β-内酰胺“增强”抗生素，与头孢吡肟（WCK 5222）联合用于治疗耐药革兰氏阴性感染。
评估头孢吡肟/齐他培南与对照药物对 24220 株革兰氏阴性菌的体外活性。
2018 年至 2019 年，连续从美国（n=9140）、西欧（W-EU；n=5929）、东欧（E-EU；n=3036）、亚太地区（APAC；n=3791）和拉丁美洲（LATAM；n=2324）的 137 家医疗中心收集了 24220 株革兰氏阴性菌。使用肉汤微量稀释法作为 SENTRY 项目的一部分对分离物进行药敏试验。头孢吡肟/齐他培南以 1:1 的比例进行测试。
头孢吡肟/齐他培南对肠杆菌科（MIC50/90 为 0.03/0.25mg/L；99.9%的抑制率在≤8mg/L）表现出高度活性，并对耐碳青霉烯肠杆菌科（CRE）分离株保持强大的活性（97.8%的抑制率在≤8mg/L）。CRE 的发生率差异很大，从美国的 1.1%到 W-EU 的 1.9%，APAC 的 3.6%和 E-EU 的 14.6%（总体为 3.9%）。总体上观察到的最常见的碳青霉烯酶基因是 blaKPC（37.6%的 CRE）、blaOXA-48 样（30.0%）和 blaNDM（23.8%）。APAC（64.8%）、E-EU（25.5%）和 LATAM（20.7%）中 CRE 对头孢他啶/阿维巴坦的耐药率升高。头孢吡肟/齐他培南对铜绿假单胞菌的抑制率为 99.2%，MIC50/90 为≤8mg/L，头孢他啶/阿维巴坦和头孢唑肟/他唑巴坦的敏感性最低，分别为 83.9%和 82.0%。头孢吡肟/齐他培南对嗜麦芽窄食单胞菌（80.0%的抑制率在≤8mg/L）和洋葱伯克霍尔德菌（89.4%的抑制率在≤8mg/L）表现出良好的活性。
头孢吡肟/齐他培南对全球范围内大量当代临床分离的革兰氏阴性菌表现出强大的体外活性。
