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Am J Perinatol 2021; 38(08): 804-809
DOI: 10.1055/s-0039-3402719
Original Article

Ceftolozane/Tazobactam in Neonates and Young Infants: The Challenges of Collecting Pharmacokinetics and Safety Data in This Vulnerable Patient Population

Jocelyn Y. Ang
1   Division of Infectious Diseases, Children's Hospital of Michigan, Detroit, Michigan
2   Department of Pediatrics, Wayne State University, Detroit, Michigan
,
Antonio Arrieta
3   Division of Pediatric Infectious Disease, Children's Hospital of Orange County, Orange, California
,
John S. Bradley
4   Division of Infectious Disease, Rady Children's Hospital, San Diego, California
5   Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California
,
Zufei Zhang
6   Merck & Co., Inc., Kenilworth, New Jersey
,
Brian Yu
6   Merck & Co., Inc., Kenilworth, New Jersey
,
Matthew L. Rizk
6   Merck & Co., Inc., Kenilworth, New Jersey
,
Matthew G. Johnson
6   Merck & Co., Inc., Kenilworth, New Jersey
,
Elizabeth G. Rhee
6   Merck & Co., Inc., Kenilworth, New Jersey
› Author Affiliations Funding Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ.
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Abstract

Objective New treatments are needed for multidrug-resistant (MDR) gram-negative infections in neonates. Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination that has broad-spectrum activity against most common gram-negative bacteria, including MDR strains. We evaluated pharmacokinetics (PK) and safety of ceftolozane/tazobactam in term and premature neonates and young infants.

Study Design This is a subgroup analysis of a phase 1, noncomparative, open-label, multicenter study that characterized the PK, safety, and tolerability of a single intravenous (IV) dose of ceftolozane/tazobactam in pediatric patients with proven/suspected gram-negative infection or receiving perioperative prophylaxis.

Results Seven patients were enrolled in Group A (birth [7 days postnatal] to < 3 months, > 32 weeks gestation) and six patients were enrolled in Group B (birth [7 days postnatal] to < 3 months, ≤ 32 weeks gestation). PK profiles in neonates and young infants were generally comparable to those of older children receiving a single IV dose of ceftolozane/tazobactam. No serious adverse events (AEs), treatment-related AEs, severe AEs, or clinically significant laboratory abnormalities were reported.

Conclusion Among term and premature neonates and young infants, PK was comparable to older children and ceftolozane/tazobactam was generally well tolerated. An adaptable and flexible study design is necessary for enrollment in neonatal PK trials.

Keywords

antibacterials - clinical trial - study design - special population - gram-negative infections


Publication History

Received: 22 August 2019

Accepted: 18 November 2019

Article published online:
07 January 2020

© 2020. Thieme. All rights reserved.

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