From the Rady Children's Hospital/University of California San Diego School of Medicine, San Diego, CA.
AstraZeneca, Alderley Park, Macclesfield, United Kingdom.
Pediatr Infect Dis J. 2019 Aug;38(8):816-824. doi: 10.1097/INF.0000000000002392.
Ceftazidime-avibactam plus metronidazole is effective in the treatment of complicated intra-abdominal infection (cIAI) in adults. This single-blind, randomized, multicenter, phase 2 study (NCT02475733) evaluated the safety, efficacy and pharmacokinetics of ceftazidime-avibactam plus metronidazole in children with cIAI.
Hospitalized children (≥3 months to <18 years) with cIAI were randomized 3:1 to receive intravenous ceftazidime-avibactam plus metronidazole, or meropenem, for a minimum of 72 hours (9 doses), with optional switch to oral therapy thereafter for a total treatment duration of 7-15 days. Safety and tolerability were assessed throughout the study, along with clinical and microbiologic outcomes, and pharmacokinetics. A blinded observer determined adverse event (AE) causality, and clinical outcomes up to the late follow-up visit.
Eighty-three children were randomized and received study drug (61 ceftazidime-avibactam plus metronidazole and 22 meropenem); most (90.4%) had a diagnosis of appendicitis. Predominant Gram-negative baseline pathogens were Escherichia coli (79.7%) and Pseudomonas aeruginosa (33.3%); 2 E. coli isolates were ceftazidime-non-susceptible. AEs occurred in 52.5% and 59.1% of patients in the ceftazidime-avibactam plus metronidazole and meropenem groups, respectively. Serious AEs occurred in 8.2% and 4.5% of patients, respectively; none was considered drug related. No deaths occurred. Favorable clinical/microbiologic responses were observed in ≥90% of patients in both treatment groups at end-of-intravenous treatment and test-of-cure visits.
Ceftazidime-avibactam plus metronidazole was well tolerated, with a safety profile similar to ceftazidime alone, and appeared effective in pediatric patients with cIAI due to Gram-negative pathogens, including ceftazidime-non-susceptible strains.
头孢他啶-阿维巴坦加甲硝唑对成人复杂性腹腔内感染（cIAI）的治疗有效。这项单盲、随机、多中心、2 期研究（NCT02475733）评估了头孢他啶-阿维巴坦加甲硝唑在患有 cIAI 的儿童中的安全性、疗效和药代动力学。
患有 cIAI 的住院儿童（≥3 个月至＜18 岁）按 3:1 随机分组，接受静脉注射头孢他啶-阿维巴坦加甲硝唑或美罗培南治疗，至少 72 小时（9 剂），随后可选择转为口服治疗，总治疗时间为 7-15 天。在整个研究过程中评估安全性和耐受性，以及临床和微生物学结局和药代动力学。盲法观察者确定不良事件（AE）的因果关系以及直至迟发随访的临床结局。
83 名儿童被随机分组并接受研究药物（头孢他啶-阿维巴坦加甲硝唑 61 例，美罗培南 22 例）；大多数（90.4%）患有阑尾炎。主要的革兰阴性基线病原体为大肠埃希菌（79.7%）和铜绿假单胞菌（33.3%）；2 株大肠埃希菌分离株对头孢他啶不敏感。头孢他啶-阿维巴坦加甲硝唑组和美罗培南组患者的 AE 发生率分别为 52.5%和 59.1%。严重 AE 发生率分别为 8.2%和 4.5%，均与药物无关。无死亡发生。在静脉治疗结束和治疗后评估时，两组患者的临床/微生物学缓解率均≥90%。
头孢他啶-阿维巴坦加甲硝唑耐受性良好，安全性与头孢他啶单独用药相似，对革兰阴性病原体引起的儿童 cIAI 似乎有效，包括对头孢他啶不敏感的菌株。
