Background: Ceftolozane/tazobactam (TOL/TAZ) is an antibiotic approved to treat complicated intraabdominal and urinary tract infections in adults and has a potentially important role in the treatment of pediatric infections. Preliminary data from an ongoing, Phase 1 pharmacokinetic (PK) study of TOL/TAZ in pediatric patients (pts) are presented.
Methods: Each pt (3 mo<18 y) received a single intravenous TOL/TAZ dose. Initial dose selection used adult PK models incorporating allometric scaling and renal function maturation to achieve exposures similar to those in adults (TOL AUC ~130-175 μg∙h/mL, TAZ AUC0-last ~24.4 μg∙h/mL). TOL concentrations >MIC of 8 μg/mL for ≥30% of an 8 hr dosing interval were also targeted. Groups 1-4 enrolled in parallel (n = 6/group); interim analysis was conducted for each group after 3 pts completed dosing.
Results: TOL PK parameters are summarized by age group (Table). Group 3 interim analysis indicated low TOL and TAZ exposure at the 18/9-mg/kg dose; TOL and TAZ doses were increased to 30/15 mg/kg for the remaining pts in Groups 3 (n = 3) and 4 (n = 5). All pts attained the TOL %T>MIC target of ≥30% above 8 μg/mL for an 8 hr dosing interval. Mean TAZ AUC0-last was 12-19 μg∙h/mL for 500-mg and 9-mg/kg doses and ~30 μg∙h/mL for 15-mg/kg doses. Sixteen adverse events (AEs) were reported across 8 pts, including 3 serious AEs deemed unrelated to study drug. Three mild AEs (dizziness in 1 pt, intermittent bradycardia and tachycardia in 1 pt) were deemed related to study drug; the AEs did not require treatment and resolved by the end of the study. There have been no premature discontinuations from study drug or the study due to AEs.
Conclusion: In this pediatric PK study, TOL/TAZ has been well tolerated. Doses of 1000/500 mg (12<18 y), 18/9 mg/kg (7<12 y), and 30/15 mg/kg (3 mo<7 y) produced TOL and TAZ exposures similar to those in adult pts.
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