Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial

Emmanuel Roilides, Negar Ashouri, John S Bradley, Matthew G Johnson, Julia Lonchar, Feng-Hsiu Su, Jennifer A Huntington, Myra W Popejoy, Mekki Bensaci, Carisa De Anda, Elizabeth G Rhee, Christopher J Bruno, Emmanuel Roilides, Negar Ashouri, John S Bradley, Matthew G Johnson, Julia Lonchar, Feng-Hsiu Su, Jennifer A Huntington, Myra W Popejoy, Mekki Bensaci, Carisa De Anda, Elizabeth G Rhee, Christopher J Bruno

Abstract

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

Methods: This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age. The primary objective was safety and tolerability. Key secondary end points included clinical cure and per-participant microbiologic response rates at end of treatment (EOT) and test of cure (TOC) visits.

Results: The microbiologic modified intent-to-treat (mMITT) population included 95 participants (ceftolozane/tazobactam, n = 71; meropenem, n = 24). The most common diagnosis and pathogen were pyelonephritis (ceftolozane/tazobactam, 84.5%; meropenem, 79.2%) and Escherichia coli (ceftolozane/tazobactam, 74.6%; meropenem, 87.5%); 5.7% (ceftolozane/tazobactam) and 4.8% (meropenem) of E. coli isolates were extended-spectrum β-lactamase-producers. Rates of adverse events were similar between treatment groups (any: ceftolozane/tazobactam, 59.0% vs. meropenem, 60.6%; drug-related: ceftolozane/tazobactam, 14.0% vs. meropenem, 15.2%; serious: ceftolozane/tazobactam, 3.0% vs. meropenem, 6.1%). Rates of clinical cure for ceftolozane/tazobactam and meropenem at EOT were 94.4% and 100% and at TOC were 88.7% and 95.8%, respectively. Rates of microbiologic eradication for ceftolozane/tazobactam and meropenem at EOT were 93.0% and 95.8%, and at TOC were 84.5% and 87.5%, respectively.

Conclusions: Ceftolozane/tazobactam had a favorable safety profile in pediatric participants with cUTI; rates of clinical cure and microbiologic eradication were high and similar to meropenem. Ceftolozane/tazobactam is a safe and effective new treatment option for children with cUTI, especially due to antibacterial-resistant Gram-negative pathogens.

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1.
FIGURE 1.
Study disposition of all randomized participants. aRandomized participants who received any amount of study drug and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture. bAll randomized participants who received any amount of study treatment. C/T indicates ceftolozane/tazobactam; mMITT, microbiologic modified intent-to-treat.
FIGURE 2.
FIGURE 2.
Clinical and microbiologic response at EOT and TOC (mMITT population). aDifference in C/T minus MEM. bThe percent difference was based on the Miettinen & Nurminen method stratified by age group with Cochran-Mantel-Haenszel weights. If there was a zero count in any class of the stratum, the groups with the lower count were pooled with the near age group stratum in the model. CI indicates confidence interval; C/T‚ ceftolozane/tazobactam; MEM, meropenem; mMITT, microbiologic modified intent-to-treat population; TOC, test of cure.

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Source: PubMed

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