Subgroup analysis of phase 2 study of ceftolozane/tazobactam in neonates and young infants with pyelonephritis

Area of Science:

• Pediatric Infectious Diseases
• Antimicrobial Pharmacokinetics and Pharmacodynamics
• Clinical Pharmacology

Background:

• Ceftolozane/tazobactam is approved for complicated urinary tract infections (cUTI) in pediatric patients.
• Limited data exist on its use in neonates and young infants (< 3 months old).
• Extrapolation of adult pharmacokinetic and clinical data to this age group may not be appropriate.

Purpose of the Study:

• To evaluate the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam versus meropenem in neonates and young infants with cUTI.
• To assess if ceftolozane/tazobactam achieves therapeutic targets in this population.

Main Methods:

• Post hoc analysis of a Phase 2, randomized, active comparator-controlled, double-blind study (NCT03230838).
• Included neonates and young infants (< 3 months) with cUTI, primarily pyelonephritis.
• Compared ceftolozane/tazobactam (n=14) with meropenem (n=6) in the microbiologic modified intent-to-treat (mMITT) population.

Main Results:

• Clinical cure rates were high in both groups (92.9% for ceftolozane/tazobactam, 100% for meropenem).
• No serious drug-related adverse events, discontinuations due to adverse events, or deaths were reported.
• Population PK analysis showed ceftolozane/tazobactam exposures similar to adults, achieving pharmacodynamic targets.

Conclusions:

• Ceftolozane/tazobactam demonstrates a favorable safety profile in neonates and young infants with cUTI.
• High clinical cure and microbiologic eradication rates were observed, comparable to meropenem.
• The drug achieves adequate exposures and pharmacodynamic targets in this vulnerable population.