Pharmacokinetics and Safety of Single Intravenous Doses of Ceftolozane/Tazobactam in Children with Proven or Suspected Gram-Negative Infection

John S. Bradley, Jocelyn Y. Ang, Antonio C. Arrieta, Kajal B. Larson, Matthew L. Rizk, Luzelena Caro, Shan Yang, Brian Yu, Matthew G. Johnson, Elizabeth G. Rhee

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Drug-resistant Gram-negative bacteria are a growing threat to children; thus new antibiotics are needed to treat infections caused by these pathogens. Ceftolozane/tazobactam is active against many Gram-negative pathogens and is approved for treatment of complicated intra-abdominal and urinary tract infections in adults, but has not been evaluated in children. Methods: This phase 1, noncomparative, open-label, multicenter study characterized the pharmacokinetics (by noncompartmental analysis), safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients (birth [7 days postnatal] to < 18 years of age) with proven/suspected Gram-negative infection or receiving perioperative prophylaxis (clinicaltrials.gov NCT02266706). Patients were enrolled into 1 of 6 age groups to receive a single, age-based ceftolozane/tazobactam dose, with timed blood sample collection for determining plasma concentrations of ceftolozane and tazobactam. Safety and tolerability were also evaluated. Results: Thirty-seven patients received study drug; 34 were included in the pharmacokinetic population. Ceftolozane and tazobactam pharmacokinetic parameters were generally comparable for patients 3 months to < 18 years of age. Patients from birth (7 days postnatal) to < 3 months of age had lower clearance than older children, likely due to the immature renal function of these young infants. No deaths, study drug-related serious adverse events, or clinically significant laboratory abnormalities were observed after administration of ceftolozane/tazobactam. Conclusions: The doses evaluated in this study yielded ceftolozane/tazobactam exposure levels generally comparable with those in adults. Single doses of ceftolozane/tazobactam were well-tolerated, and no safety concerns were identified. These data informed pharmacokinetic/pharmacodynamic models to derive pediatric dose recommendations for phase 2 ceftolozane/tazobactam clinical trials.

Original languageEnglish
Pages (from-to)1130-1136
Number of pages7
JournalPediatric Infectious Disease Journal
Volume37
Issue number11
DOIs
StatePublished - Nov 1 2018

Keywords

  • Pseudomonas
  • beta-lactamase inhibitor
  • children
  • clinical trial
  • tolerability

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