Safety and Efficacy of Ceftazidime-Avibactam in the Treatment of Children ≥3 Months to
Safety and Efficacy of Ceftazidime-Avibactam in the Treatment of Children ≥3 Months to
复制标题
DOI：
10.1097/inf.0000000000002395
复制
发表时间：
2019-09-01
影响因子：
3.6
通讯作者：
Gardner, Annie
中科院分区：
文献类型：
--
作者：
Bradley, John S.;Roilides, Emmanuel;Gardner, Annie
背景：头孢他啶-阿巴坦对成人复杂性尿路感染(CUTI)有效且耐受性良好，但尚未在儿童cUTI中进行评估。方法：这项单盲、多中心、主动对照的2期研究(NCT02497781)将3个月至72小时的儿童随机分为两组，随后进行可选的口服换药。总疗程7~14d。主要目的是评估安全性。次要目标包括描述性疗效和药物动力学。一位盲人观察者确定了不良事件(AE)的因果关系和临床结果，直到最后一次随访(最后一次静脉/口服治疗后20-36天)。结果：总共有95名儿童接受了1剂静脉注射研究药物(头孢他啶-阿维巴坦67例，头孢吡肟28例)。革兰氏阴性菌以大肠埃希菌为主(92.2%)。头孢他啶-阿维巴坦组和头孢吡肟组分别有53.7%和53.6%的患者发生了急性呼吸窘迫综合征。严重不良反应发生率分别为11.9%(头孢他啶-阿巴坦)和7.1%(头孢吡肟)。1例严重AE(头孢他啶-阿巴坦组)被认为与药物有关。在微生物学意向治疗分析集中，两组在IV期末均观察到良好的临床有效率和95%，在治愈测试时，头孢他啶-阿维巴坦组和头孢吡肟组分别保持88.9%和82.6%。在治愈试验中，每个患者的良好微生物学反应(头孢他啶-阿维巴坦)为79.6%，头孢吡肟(头孢吡肟)为60.9%。结论：头孢他啶-阿维巴坦在儿童cUTI中耐受性良好，安全性与成人cUTI和单用头孢他啶一致，且因革兰氏阴性菌而对儿童cUTI有效。
Background: Ceftazidime-avibactam is effective and well tolerated in adults with complicated urinary tract infection (cUTI), but has not been evaluated in children with cUTI. Methods: This single-blind, multicenter, active-controlled, phase 2 study (NCT02497781) randomized children >= 3 months to = 72 hours, with subsequent optional oral switch. Total treatment duration was 7-14 days. Primary objective was assessment of safety. Secondary objectives included descriptive efficacy and pharmacokinetics. A blinded observer determined adverse event (AE) causality and clinical outcomes up to the late follow-up visit (20-36 days after the last dose of IV/oral therapy). Results: In total, 95 children received >= 1 dose of IV study drug (ceftazidime-avibactam, n = 67; cefepime, n = 28). The predominant baseline Gram-negative uropathogen was Escherichia coli (92.2%). AEs occurred in 53.7% and 53.6% patients in the ceftazidime-avibactam and cefepime groups, respectively. Serious AEs occurred in 11.9% (ceftazidime-avibactam) and 7.1% (cefepime) patients. One serious AE (ceftazidime-avibactam group) was considered drug related. In the microbiologic intent-to-treat analysis set, favorable clinical response rates >95% were observed for both groups at end-of-IV and remained 88.9% (ceftazidime-avibactam) and 82.6% (cefepime) at test-of-cure. Favorable per-patient microbiologic response at test-of-cure was 79.6% (ceftazidime-avibactam) and 60.9% (cefepime). Conclusions: Ceftazidime-avibactam was well tolerated in children with cUTI, with a safety profile consistent with that of adults with cUTI and of ceftazidime alone, and appeared effective in children with cUTI due to Gram-negative pathogens.