Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis

Antonio C. Arrieta, Jocelyn Y. Ang, Zufei Zhang, Kajal B. Larson, Brian Yu, Matthew G. Johnson, Elizabeth G. Rhee, Ed H. Feng, Matthew L. Rizk

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: The antipseudomonal cephalosporin/β-lactamase inhibitor combination ceftolozane/tazobactam could be a potential treatment option for cystic fibrosis (CF) pulmonary exacerbations. The pharmacokinetics (PK) of ceftolozane/tazobactam in children with CF merits further evaluation. Methods: This is a retrospective subgroup analysis of a phase 1, noncomparative trial that characterized PK, safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients. This analysis compares ceftolozane and tazobactam plasma PK parameters, estimated from a population PK model, between patients with and without CF enrolled in that trial. Individual attainment of PK/pharmacodynamic (PD) targets of ceftolozane and tazobactam (free ceftolozane concentration >4 µg/mL for >30% and free tazobactam concentration >1 µg/mL for 20% of the dosing interval) in patients with and without CF were evaluated. Results: The study enrolled 18 patients aged greater than or equal to 2 to less than 18 years old, which included 9 with CF. Weight-normalized ceftolozane PK parameters were similar between patients with CF (clearance: 0.16 L/h/kg, half-life: 1.54 hours, volume of distribution: 0.26 L/kg) and without CF (clearance: 0.15 L/h/kg, half-life: 1.62 hours, volume of distribution: 0.26 L/kg), as were most weight-normalized tazobactam PK parameters. Weight-normalized tazobactam clearance was higher in patients with CF (0.73 L/h/kg) than patients without CF (0.42 L/h/kg). All patients achieved the prespecified PK/PD targets for ceftolozane and tazobactam. Conclusions: This retrospective analysis demonstrated generally similar weight-normalized plasma PK parameters for ceftolozane and tazobactam among children with and without CF; thus, projected doses for treatment of pediatric hospital-acquired/ventilator-associated pneumonia, which are higher than the pediatric complicated urinary tract infection/intra-abdominal infection doses, may be appropriate for treatment of CF pulmonary exacerbation.

Original languageEnglish
Pages (from-to)2025-2032
Number of pages8
JournalPediatric Pulmonology
Issue number8
StatePublished - Aug 1 2020


  • Pseudomonas
  • children
  • clinical trials
  • cystic fibrosis
  • modeling
  • population pharmacokinetics
  • pulmonary exacerbations


Dive into the research topics of 'Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis'. Together they form a unique fingerprint.

Cite this