Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection
Open Access
- 29 March 2023
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in The Pediatric Infectious Disease Journal
- Vol. 42 (7), 557-563
- https://doi.org/10.1097/inf.0000000000003911
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 (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. Conclusion: 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.Keywords
This publication has 17 references indexed in Scilit:
- Pediatric extended spectrum β‐lactamase infection: Community‐acquired infection and treatment optionsPediatrics International, 2016
- Epidemiology and Antimicrobial Susceptibility of Gram-Negative Pathogens Causing Intra-abdominal Infections in Pediatric Patients in Europe—SMART 2011–2014Journal of the Pediatric Infectious Diseases Society, 2016
- Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI)Clinical Infectious Diseases, 2015
- Etiology, Extended-spectrum β-lactamase Rates and Antimicrobial Susceptibility of Gram-negative Bacilli Causing Intra-abdominal Infections in Patients in General Pediatric and Pediatric Intensive Care Units—Global Data From The Study for Monitoring Antimicrobial Resistance Trends 2008 to 2010The Pediatric Infectious Disease Journal, 2013
- Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO studyWorld Journal of Emergency Surgery, 2012
- Diagnosis and Management of Complicated Intra-abdominal Infection in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of AmericaClinical Infectious Diseases, 2010
- Definition and Classification of Intra-abdominal InfectionsJournal of Chemotherapy, 2009
- Community-acquired complicated intra-abdominal infections in children hospitalized during 1995–2004 at a paediatric surgery departmentScandinavian Journal of Infectious Diseases, 2009
- Intraabdominal infections in infants and children: Descriptions and definitionsPediatric Critical Care Medicine, 2005
- Comparative analysis of two ratesStatistics in Medicine, 1985