Pfizer, Groton, Connecticut, USA
AstraZeneca, Alderley Park, United Kingdom.
Antimicrob Agents Chemother. 2018 Jun 26;62(7). doi: 10.1128/AAC.02584-17. Print 2018 Jul.
The increasing prevalence of multidrug-resistant Gram-negative pathogens has generated a requirement for new treatment options. Avibactam, a novel non-β-lactam-β-lactamase inhibitor, restores the activity of ceftazidime against Ambler class A, C, and some class D β-lactamase-producing strains of and The activities of ceftazidime-avibactam versus comparators were evaluated against 1,440 clinical isolates obtained in a phase 3 clinical trial in patients with complicated intra-abdominal infections (cIAI; ClinicalTrials.gov identifier NCT01499290). Overall, activities were determined for 803 , 70 , 304 Gram-positive aerobic, and 255 anaerobic isolates obtained from 1,066 randomized patients at baseline. Susceptibility was determined by broth microdilution. The most commonly isolated Gram-negative, Gram-positive, and anaerobic pathogens were ( = 549), ( = 130), and ( = 96), respectively. Ceftazidime-avibactam was highly active against isolates of , with an overall MIC of 0.25 mg/liter. In contrast, the MIC for ceftazidime alone was 32 mg/liter. The MIC value for ceftazidime-avibactam (4 mg/liter) was one dilution lower than that of ceftazidime alone (8 mg/liter) against isolates of The ceftazidime-avibactam MIC for 109 ceftazidime-nonsusceptible isolates was 2 mg/liter, and the MIC range for 6 ceftazidime-nonsusceptible isolates was 8 to 32 mg/liter. The MIC values were within the range of susceptibility for the study drugs permitted per the protocol in the phase 3 study to provide coverage for aerobic Gram-positive and anaerobic pathogens. These findings demonstrate the activity of ceftazidime-avibactam against bacterial pathogens commonly observed in cIAI patients, including ceftazidime-nonsusceptible (This study has been registered at ClinicalTrials.gov under identifier NCT01499290.).
革兰氏阴性耐药菌的发病率不断上升，这就需要新的治疗方法。阿维巴坦是一种新型的非β-内酰胺类β-内酰胺酶抑制剂，它恢复了头孢他啶对安布勒分类 A、C 和一些 D 类β-内酰胺酶产生菌的活性。在一项 3 期临床试验中，评估了头孢他啶-阿维巴坦与对照药物对 1440 例复杂性腹腔内感染（cIAI；ClinicalTrials.gov 标识符 NCT01499290）患者的临床分离株的活性。总体而言，对 1066 例随机患者基线时获得的 803 株、70 株、304 株革兰氏阳性需氧菌和 255 株厌氧菌进行了 803 株、70 株、304 株革兰氏阳性需氧菌和 255 株厌氧菌的活性测定。通过肉汤微量稀释法确定敏感性。最常见的分离革兰氏阴性、革兰氏阳性和厌氧菌病原体分别为 （=549）、（=130）和 （=96）。头孢他啶-阿维巴坦对 分离株高度活跃，总体 MIC 为 0.25 毫克/升。相比之下，单独使用头孢他啶的 MIC 值为 32 毫克/升。与单独使用头孢他啶（8 毫克/升）相比，头孢他啶-阿维巴坦（4 毫克/升）的 MIC 值低一个稀释度。对 109 株头孢他啶不敏感的 分离株，头孢他啶-阿维巴坦的 MIC 值为 2 毫克/升，6 株头孢他啶不敏感的 分离株的 MIC 值范围为 8 至 32 毫克/升。这些 MIC 值在 3 期研究方案允许的研究药物的敏感性范围内，为需氧革兰氏阳性和厌氧菌病原体提供了覆盖。这些发现表明，头孢他啶-阿维巴坦对 cIAI 患者中常见的细菌病原体具有 活性，包括头孢他啶不敏感的 （本研究已在 ClinicalTrials.gov 注册，标识符为 NCT01499290）。
