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Abstract：
BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.
METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.
RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: -14.3; 95% confidence interval: -26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: -19.1; 95% confidence interval: -30.18 to -2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol.
CONCLUSIONS: Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious.
METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.
RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: -14.3; 95% confidence interval: -26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: -19.1; 95% confidence interval: -30.18 to -2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol.
CONCLUSIONS: Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious.
摘要：
背景：头孢洛赞/他唑巴坦，头孢菌素-β-内酰胺酶抑制剂组合，已被批准用于治疗复杂的尿路感染和复杂的腹腔内感染（cIAI）。评估头孢洛扎/他唑巴坦在cIAI儿科参与者中的安全性和有效性。
方法：这项2期研究（NCT03217136）将参与者随机分为头孢特洛赞/他唑巴坦+甲硝唑或美罗培南，用于儿科参与者（<18岁）的cIAI治疗。主要目的是评估头孢特洛赞/他唑巴坦+甲硝唑静脉注射的安全性和耐受性。治疗结束时的临床治愈（EOT）和治愈测试（TOC）访问是次要终点。
结果：改良意向治疗（MITT）人群包括91名参与者（头孢特洛赞/他唑巴坦+甲硝唑，n=70；美罗培南，n=21)。复杂性阑尾炎是最常见的诊断（93.4％）；大肠埃希菌是最常见的病原体（65.9％）。不良事件（AE）发生在80.0%和61.9%的参与者接受头孢洛赞/他唑巴坦+甲硝唑和美罗培南，在接受头孢特洛赞/他唑巴坦+甲硝唑和美罗培南的参与者中，药物相关的不良事件发生率分别为18.6%和14.3%，严重不良事件发生率分别为11.4%和0%，分别。未发生药物相关严重AE或因药物相关AE而停药。头孢洛扎/他唑巴坦甲硝唑和美罗培南在EOT的临床治愈率分别为80.0%和95.2%（差异：-14.3；95%置信区间：-26.67至4.93），在TOC的临床治愈率分别为80.0%和100.0%（差异：-19.1；95%置信区间：-30.18至-2.89），分别；在TOC下头孢洛赞/他唑巴坦甲硝唑的14项临床失败中，有6项是不确定的反应，被认为是方案失败。
结论：在cIAI的儿科参与者中，头孢特洛扎/他唑巴坦+甲硝唑的耐受性良好，其安全性与成人的既定安全性相似。在这种描述性功效分析中，头孢洛赞/他唑巴坦+甲硝唑似乎有效。
方法：这项2期研究（NCT03217136）将参与者随机分为头孢特洛赞/他唑巴坦+甲硝唑或美罗培南，用于儿科参与者（<18岁）的cIAI治疗。主要目的是评估头孢特洛赞/他唑巴坦+甲硝唑静脉注射的安全性和耐受性。治疗结束时的临床治愈（EOT）和治愈测试（TOC）访问是次要终点。
结果：改良意向治疗（MITT）人群包括91名参与者（头孢特洛赞/他唑巴坦+甲硝唑，n=70；美罗培南，n=21)。复杂性阑尾炎是最常见的诊断（93.4％）；大肠埃希菌是最常见的病原体（65.9％）。不良事件（AE）发生在80.0%和61.9%的参与者接受头孢洛赞/他唑巴坦+甲硝唑和美罗培南，在接受头孢特洛赞/他唑巴坦+甲硝唑和美罗培南的参与者中，药物相关的不良事件发生率分别为18.6%和14.3%，严重不良事件发生率分别为11.4%和0%，分别。未发生药物相关严重AE或因药物相关AE而停药。头孢洛扎/他唑巴坦甲硝唑和美罗培南在EOT的临床治愈率分别为80.0%和95.2%（差异：-14.3；95%置信区间：-26.67至4.93），在TOC的临床治愈率分别为80.0%和100.0%（差异：-19.1；95%置信区间：-30.18至-2.89），分别；在TOC下头孢洛赞/他唑巴坦甲硝唑的14项临床失败中，有6项是不确定的反应，被认为是方案失败。
结论：在cIAI的儿科参与者中，头孢特洛扎/他唑巴坦+甲硝唑的耐受性良好，其安全性与成人的既定安全性相似。在这种描述性功效分析中，头孢洛赞/他唑巴坦+甲硝唑似乎有效。
