Safety and Efficacy of Ceftazidime-Avibactam in the Treatment of Children ≥3 Months to <18 Years With Complicated Urinary Tract Infection: Results from a Phase 2 Randomized, Controlled Trial

Pediatr Infect Dis J. 2019 Sep;38(9):920-928. doi: 10.1097/INF.0000000000002395.


Background: Ceftazidime-avibactam is effective and well tolerated in adults with complicated urinary tract infection (cUTI), but has not been evaluated in children with cUTI.

Methods: This single-blind, multicenter, active-controlled, phase 2 study (NCT02497781) randomized children ≥3 months to <18 years with cUTI (3:1) to receive intravenous (IV) ceftazidime-avibactam or cefepime for ≥72 hours, with subsequent optional oral switch. Total treatment duration was 7-14 days. Primary objective was assessment of safety. Secondary objectives included descriptive efficacy and pharmacokinetics. A blinded observer determined adverse event (AE) causality and clinical outcomes up to the late follow-up visit (20-36 days after the last dose of IV/oral therapy).

Results: In total, 95 children received ≥1 dose of IV study drug (ceftazidime-avibactam, n = 67; cefepime, n = 28). The predominant baseline Gram-negative uropathogen was Escherichia coli (92.2%). AEs occurred in 53.7% and 53.6% patients in the ceftazidime-avibactam and cefepime groups, respectively. Serious AEs occurred in 11.9% (ceftazidime-avibactam) and 7.1% (cefepime) patients. One serious AE (ceftazidime-avibactam group) was considered drug related. In the microbiologic intent-to-treat analysis set, favorable clinical response rates >95% were observed for both groups at end-of-IV and remained 88.9% (ceftazidime-avibactam) and 82.6% (cefepime) at test-of-cure. Favorable per-patient microbiologic response at test-of-cure was 79.6% (ceftazidime-avibactam) and 60.9% (cefepime).

Conclusions: Ceftazidime-avibactam was well tolerated in children with cUTI, with a safety profile consistent with that of adults with cUTI and of ceftazidime alone, and appeared effective in children with cUTI due to Gram-negative pathogens.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Azabicyclo Compounds / administration & dosage*
  • Azabicyclo Compounds / adverse effects
  • Azabicyclo Compounds / pharmacokinetics
  • Ceftazidime / administration & dosage*
  • Ceftazidime / adverse effects
  • Ceftazidime / pharmacokinetics
  • Child
  • Child, Preschool
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial
  • Escherichia coli / drug effects
  • Female
  • Humans
  • Infant
  • Male
  • Single-Blind Method
  • Urinary Tract Infections / complications
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / microbiology*


  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime

Associated data