Cargando…

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

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 cU...

Descripción completa

Detalles Bibliográficos
Autores principales: Roilides, Emmanuel, Ashouri, Negar, Bradley, John S., Johnson, Matthew G., Lonchar, Julia, Su, Feng-Hsiu, Huntington, Jennifer A., Popejoy, Myra W., Bensaci, Mekki, De Anda, Carisa, Rhee, Elizabeth G., Bruno, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990597/
https://www.ncbi.nlm.nih.gov/pubmed/36689671
http://dx.doi.org/10.1097/INF.0000000000003832
_version_ 1784901968458678272
author Roilides, Emmanuel
Ashouri, Negar
Bradley, John S.
Johnson, Matthew G.
Lonchar, Julia
Su, Feng-Hsiu
Huntington, Jennifer A.
Popejoy, Myra W.
Bensaci, Mekki
De Anda, Carisa
Rhee, Elizabeth G.
Bruno, Christopher J.
author_facet Roilides, Emmanuel
Ashouri, Negar
Bradley, John S.
Johnson, Matthew G.
Lonchar, Julia
Su, Feng-Hsiu
Huntington, Jennifer A.
Popejoy, Myra W.
Bensaci, Mekki
De Anda, Carisa
Rhee, Elizabeth G.
Bruno, Christopher J.
author_sort Roilides, Emmanuel
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9990597
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-99905972023-03-08 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 Roilides, Emmanuel Ashouri, Negar Bradley, John S. Johnson, Matthew G. Lonchar, Julia Su, Feng-Hsiu Huntington, Jennifer A. Popejoy, Myra W. Bensaci, Mekki De Anda, Carisa Rhee, Elizabeth G. Bruno, Christopher J. Pediatr Infect Dis J Antimicrobial Reports 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. Lippincott Williams & Wilkins 2023-01-23 2023-04 /pmc/articles/PMC9990597/ /pubmed/36689671 http://dx.doi.org/10.1097/INF.0000000000003832 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Antimicrobial Reports
Roilides, Emmanuel
Ashouri, Negar
Bradley, John S.
Johnson, Matthew G.
Lonchar, Julia
Su, Feng-Hsiu
Huntington, Jennifer A.
Popejoy, Myra W.
Bensaci, Mekki
De Anda, Carisa
Rhee, Elizabeth G.
Bruno, Christopher J.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Antimicrobial Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990597/
https://www.ncbi.nlm.nih.gov/pubmed/36689671
http://dx.doi.org/10.1097/INF.0000000000003832
work_keys_str_mv AT roilidesemmanuel safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT ashourinegar safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT bradleyjohns safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT johnsonmatthewg safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT loncharjulia safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT sufenghsiu safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT huntingtonjennifera safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT popejoymyraw safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT bensacimekki safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT deandacarisa safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT rheeelizabethg safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial
AT brunochristopherj safetyandefficacyofceftolozanetazobactamversusmeropeneminneonatesandchildrenwithcomplicatedurinarytractinfectionincludingpyelonephritisaphase2randomizedclinicaltrial