Pfizer, Sandwich, Kent, UK.
AstraZeneca, Alderley Park, Macclesfield, UK.
Drug Saf. 2020 Aug;43(8):751-766. doi: 10.1007/s40264-020-00934-3.
Ceftazidime-avibactam combines the established anti-pseudomonal cephalosporin, ceftazidime, with the novel non-β-lactam β-lactamase inhibitor, avibactam.
The aim of this study was to evaluate the safety of ceftazidime-avibactam in adults using pooled data from two phase II (NCT00690378, NCT00752219) and five phase III (NCT01499290, NCT01726023, NCT01644643, NCT01808093 and NCT01595438/NCT01599806) clinical studies.
Safety data from seven multicentre, randomised, active-comparator studies were pooled by study group at the patient level for descriptive analyses, comprising patients with complicated urinary tract infection (cUTI), including pyelonephritis, complicated intra-abdominal infection (cIAI), or nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), treated with ceftazidime-avibactam ± metronidazole or comparator.
In total, 4050 patients (ceftazidime-avibactam ± metronidazole, n = 2024; comparator, n = 2026) were included in the pooled analysis. Adverse events (AEs) up to the last study visit occurred in 996 (49.2%) and 965 (47.6%) patients treated with ceftazidime-avibactam ± metronidazole and comparator, respectively. The most common AEs across treatment groups were diarrhoea, nausea, headache, vomiting and pyrexia. There were few discontinuations due to AEs (2.5% and 1.7% for ceftazidime-avibactam ± metronidazole and comparators, respectively). Overall rates of serious AEs were 8.7% for ceftazidime-avibactam ± metronidazole and 7.2% for comparators; respective rates of AEs with an outcome of death were 2.0% and 1.8%. AEs considered causally related to the study drug or procedures occurred in 10.7% and 9.6% of patients treated with ceftazidime-avibactam ± metronidazole and comparators; the most common drug-related AEs in both groups were diarrhoea, headache, nausea and increased alanine aminotransferase. No impact to the safety profile of ceftazidime-avibactam ± metronidazole was found with regard to intrinsic factors, such as age or renal function at baseline, or extrinsic factors, such as geographical origin. Potentially clinically significant changes in laboratory parameters were infrequent with no trends or safety concerns identified.
The observed safety profile of ceftazidime-avibactam across infection types is consistent with the established safety profile of ceftazidime monotherapy and no new safety findings were identified. This analysis supports the use of ceftazidime-avibactam as a treatment option in adults with cUTI, cIAI and NP, including VAP.
头孢他啶-阿维巴坦组合了已确立的抗假单胞菌头孢菌素头孢他啶和新型非β-内酰胺β-内酰胺酶抑制剂阿维巴坦。
本研究旨在使用来自两项 II 期（NCT00690378、NCT00752219）和五项 III 期（NCT01499290、NCT01726023、NCT01644643、NCT01808093 和 NCT01595438/NCT01599806）临床研究的汇总数据评估成人使用头孢他啶-阿维巴坦的安全性。
通过研究组对来自七项多中心、随机、阳性对照研究的安全性数据进行了患者水平的汇总描述性分析，包括患有复杂性尿路感染（cUTI）、包括肾盂肾炎、复杂性腹腔内感染（cIAI）或医院获得性肺炎（NP）、包括呼吸机相关性肺炎（VAP）的患者，接受头孢他啶-阿维巴坦±甲硝唑或对照药物治疗。
在总共 4050 名患者（头孢他啶-阿维巴坦±甲硝唑，n=2024；对照药物，n=2026）中进行了汇总分析。在最后一次研究访问时发生不良事件（AE）的患者分别为 996（49.2%）和 965（47.6%）名接受头孢他啶-阿维巴坦±甲硝唑和对照药物治疗的患者。治疗组中最常见的 AE 是腹泻、恶心、头痛、呕吐和发热。因 AE 而停药的患者很少（头孢他啶-阿维巴坦±甲硝唑和对照药物分别为 2.5%和 1.7%）。总体严重 AE 发生率分别为头孢他啶-阿维巴坦±甲硝唑 8.7%和对照药物 7.2%；各自因 AE 导致死亡的发生率分别为 2.0%和 1.8%。考虑与研究药物或程序相关的 AE 分别发生在接受头孢他啶-阿维巴坦±甲硝唑和对照药物治疗的 10.7%和 9.6%的患者中；两组中最常见的药物相关 AE 是腹泻、头痛、恶心和丙氨酸氨基转移酶升高。没有发现内在因素（如基线时的年龄或肾功能）或外在因素（如地理位置）对头孢他啶-阿维巴坦±甲硝唑安全性特征产生影响。实验室参数的潜在临床显著变化不常见，未发现任何趋势或安全性问题。
在各种感染类型中观察到的头孢他啶-阿维巴坦安全性特征与头孢他啶单药治疗的既定安全性特征一致，未发现新的安全性发现。这项分析支持将头孢他啶-阿维巴坦作为成人复杂性尿路感染、复杂性腹腔内感染和医院获得性肺炎（包括呼吸机相关性肺炎）的治疗选择。
