Roilides Emmanuel, Bradley John S, Lonchar Julia, Huntington Jennifer A, Wickremasingha Prachi, Su Feng-Hsiu, Bruno Christopher J, Johnson Matthew G
Third Department of Pediatrics, Infectious Diseases Unit, School of Medicine, Aristotle University and Hippokration General Hospital , Thessaloniki, Greece.
Department of Pediatrics, University of California, San Diego School of Medicine and Rady Children's Hospital of San Diego , San Diego, California, USA.
Microbiol Spectr. 2023 Sep 12;11(5):e0180023. doi: 10.1128/spectrum.01800-23.
Ceftolozane/tazobactam is approved for the treatment of patients from birth to <18 y old with complicated urinary tract infections (cUTI). This post hoc analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam compared with meropenem in neonates and young infants. NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind study of patients from birth to <18 y of age with cUTI, including pyelonephritis, given ceftolozane/tazobactam or meropenem in a 3:1 ratio. This subset analysis included only neonates and young infants < 3 mo of age. The microbiologic modified intent-to-treat population (mMITT) included 20 patients (ceftolozane/tazobactam, = 14; meropenem, = 6). All patients had pyelonephritis at baseline; two patients in each treatment group had bacteremia (overall 4/20, 20%). was the most common baseline pathogen (overall 16/20, 80%). Safety and efficacy results were similar between treatment groups and consistent with the overall pediatric population. There were no serious drug-related adverse events (AEs), no discontinuations due to AEs, and no AEs leading to death in either treatment group. For the ceftolozane/tazobactam and meropenem treatment groups, clinical cure rates in the mMITT population were 92.9% and 100%, respectively. The population PK analysis of neonates and young infants demonstrated similar ceftolozane and tazobactam exposures to those of adults, achieving pharmacodynamic targets associated with clinical and microbiologic cure. Ceftolozane/tazobactam has a favorable safety profile and achieves high clinical cure and microbiologic eradication rates in neonates and young infants < 3 mo of age with cUTI and pyelonephritis. IMPORTANCE Extrapolation of antibacterial agent pharmacokinetics from adults to newborns and young infants may not be appropriate; similarly, the clinical manifestations of infectious diseases and outcomes following antibacterial treatment may not be similar. Ceftolozane/tazobactam is an antibacterial drug combination active against and other multidrug-resistant gram-negative bacteria. A clinical study led to the approval for ceftolozane/tazobactam in patients from birth to 18 y of age who have complicated urinary tract infections, including those with serious kidney infections. Based on data collected during that clinical study, we compared newborns and young infants who were treated with ceftolozane/tazobactam (14 patients) and those who were treated with meropenem (6 patients). We found that ceftolozane/tazobactam treatment of newborns and young infants up to 3 mo of age who have complicated urinary tract infections demonstrated a favorable safety profile and high clinical cure and microbiologic eradication rates, similar to meropenem.
头孢洛扎/他唑巴坦已被批准用于治疗出生至未满18岁的复杂性尿路感染（cUTI）患者。本事后分析评估了头孢洛扎/他唑巴坦与美罗培南相比在新生儿和婴幼儿中的安全性、疗效及药代动力学（PK）。NCT03230838是一项2期、随机、活性对照、双盲研究，纳入了出生至未满18岁的cUTI患者（包括肾盂肾炎），按3:1的比例给予头孢洛扎/他唑巴坦或美罗培南治疗。该亚组分析仅纳入了年龄小于3个月的新生儿和婴幼儿。微生物学改良意向性治疗人群（mMITT）包括20例患者（头孢洛扎/他唑巴坦组，n = 14；美罗培南组，n = 6）。所有患者基线时均患有肾盂肾炎；每个治疗组有2例患者发生菌血症（共4/20，20%）。大肠埃希菌是最常见的基线病原体（共16/20，80%）。治疗组之间的安全性和疗效结果相似，且与总体儿科人群一致。两个治疗组均未发生严重的药物相关不良事件（AE），无因AE停药的情况，也没有AE导致死亡。对于头孢洛扎/他唑巴坦组和美罗培南组，mMITT人群中的临床治愈率分别为92.9%和100%。对新生儿和婴幼儿的群体PK分析表明，头孢洛扎和他唑巴坦的暴露量与成人相似，达到了与临床和微生物学治愈相关的药效学目标。头孢洛扎/他唑巴坦具有良好的安全性，在年龄小于3个月、患有cUTI和肾盂肾炎的新生儿和婴幼儿中可实现较高的临床治愈率和微生物清除率。重要性将抗菌药物的药代动力学从成人外推至新生儿和婴幼儿可能并不合适；同样，传染病的临床表现及抗菌治疗后的结局可能也不相似。头孢洛扎/他唑巴坦是一种对大肠埃希菌和其他多重耐药革兰阴性菌有效的抗菌药物组合。一项临床研究使得头孢洛扎/他唑巴坦被批准用于患有复杂性尿路感染（包括严重肾脏感染）的出生至18岁患者。基于该临床研究期间收集的数据，我们比较了接受头孢洛扎/他唑巴坦治疗的新生儿和婴幼儿（14例患者）与接受美罗培南治疗的新生儿和婴幼儿（6例患者）。我们发现，头孢洛扎/他唑巴坦治疗年龄至3个月的患有复杂性尿路感染的新生儿和婴幼儿显示出良好的安全性以及较高的临床治愈率和微生物清除率，与美罗培南相似。
