IHMA Europe Sàrl, Monthey, Switzerland.
Allecra Therapeutics SAS, St-Louis, France.
Antimicrob Agents Chemother. 2019 Jun 24;63(7). doi: 10.1128/AAC.00514-19. Print 2019 Jul.
Enmetazobactam, formerly AAI101, is a novel penicillanic acid sulfone extended-spectrum β-lactamase (ESBL) inhibitor. The combination of enmetazobactam with cefepime has entered clinical trials to assess safety and efficacy in patients with complicated urinary tract infections. Here, the activity of cefepime-enmetazobactam was determined for 1,993 clinical isolates of and collected in the United States and Europe during 2014 and 2015. Enmetazobactam at a fixed concentration of 8 μg/ml lowered the cefepime MIC from 16 to 0.12 μg/ml for , from >64 to 0.5 μg/ml for , from 16 to 1 μg/ml for , and from 0.5 to 0.25 μg/ml for Enmetazobactam did not enhance the potency of cefepime against Applying the Clinical and Laboratory Standards Institute susceptible-dose-dependent (SDD) breakpoint of 8 μg/ml to cefepime-enmetazobactam for comparative purposes resulted in cumulative inhibitions of 99.9% for , 96.4% for , 97.0% for , 100% for , 98.1% for all assessed, and 82.8% for Comparator susceptibilities for all were 99.7% for ceftazidime-avibactam, 96.2% for meropenem, 90.7% for ceftolozane-tazobactam, 87% for cefepime (SDD breakpoint), 85.7% for piperacillin-tazobactam, and 81.2% for ceftazidime. For the subset of ESBL-producing isolates, the addition of 8 μg/ml enmetazobactam to cefepime lowered the MIC from >64 to 1 μg/ml, whereas the shift for 8 μg/ml tazobactam was from >64 to 8 μg/ml. Cefepime-enmetazobactam may represent a novel carbapenem-sparing option for empirical treatment of serious Gram-negative infections in settings where ESBL-producing are expected.
恩美曲妥珠单抗，以前称为 AAI101，是一种新型青霉素酸砜扩展谱β-内酰胺酶（ESBL）抑制剂。将恩美曲妥珠单抗与头孢吡肟联合用于临床试验，以评估其在患有复杂尿路感染的患者中的安全性和疗效。在这里，测定了在 2014 年和 2015 年期间在美国和欧洲收集的 1993 株 和 临床分离株的头孢吡肟-恩美曲妥珠单抗活性。固定浓度为 8μg/ml 的恩美曲妥珠单抗将头孢吡肟对 的 MIC 从 16 降至 0.12μg/ml，对 >64 至 0.5μg/ml，对 16 至 1μg/ml，对 0.5 至 0.25μg/ml。恩美曲妥珠单抗没有增强头孢吡肟对 的效力。为了比较的目的，将头孢吡肟-恩美曲妥珠单抗的临床和实验室标准协会敏感剂量依赖性（SDD）折点应用于 8μg/ml，结果对所有评估的 ，累积抑制率为 99.9%， 为 96.4%， 为 97.0%， 为 100%， 为 98.1%，所有 为 82.8%。所有 的比较药敏率为头孢他啶-阿维巴坦 99.7%，美罗培南 96.2%，头孢洛扎坦-他唑巴坦 90.7%，头孢吡肟（SDD 折点）87%，哌拉西林-他唑巴坦 85.7%，头孢他啶 81.2%。对于产 ESBL 的 分离株亚组，将 8μg/ml 的恩美曲妥珠单抗添加到头孢吡肟中，将 MIC 从 >64 降低至 1μg/ml，而 8μg/ml 的他唑巴坦的变化为 >64 至 8μg/ml。头孢吡肟-恩美曲妥珠单抗可能是一种新的碳青霉烯类药物节约选择，用于治疗预期产 ESBL 的 引起的严重革兰氏阴性感染的经验性治疗。
