1965. Pharmacokinetics and Safety of Ceftolozane/Tazobactam in Adolescents and Young Children with Proven or Suspected Gram-negative Infection
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • 150101798_Pediatric PK PD_FINAL.pdf (401.5 kB)
  • 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.

    Kajal Larson, PhD1, Brian Yu, PharmD1, Adedayo Adedoyin, PhD1, Jennifer A. Huntington, PharmD1, Luzelena Caro, Ph.D.1, Alan Xiao, PhD1, Dianne DeLucia, MS1, Ellie Hershberger, PharmD1 and Elizabeth Rhee, MD2, (1)Merck & Co., Inc., Kenilworth, NJ, (2)Merck & Co. Inc., Kenilworth, NJ

    Disclosures:

    K. Larson, Merck & Co., Inc.: Employee , Salary

    B. Yu, Merck & Co., Inc.: Employee , Salary

    A. Adedoyin, Merck & Co., Inc.: Employee , Salary

    J. A. Huntington, Merck & Co., Inc.: Employee , Salary

    L. Caro, Merck & Co., Inc.: Employee , Salary

    A. Xiao, Merck & Co., Inc.: Employee , Salary

    D. DeLucia, Merck & Co., Inc.: Employee , Salary

    E. Hershberger, Merck & Co., Inc.: Employee , Salary

    E. Rhee, Merck & Co. Inc.: Employee and Shareholder , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.