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
Journal
Pediatric Infectious Disease Journal
Journal Volume
38
Journal Issue
9
Pages
920-928
Date Issued
2019
Author(s)
Bradley J.S.
Roilides E.
Broadhurst H.
Cheng K.
Mascasullo V.
Newell P.
Stone G.G.
Tawadrous M.
Wajsbrot D.
Yates K.
Gardner A.
Abstract
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. ? 2019 Wolters Kluwer Health, Inc. All rights reserved.
Subjects
cefepime; ceftazidime-avibactam; complicated urinary tract infection; pediatric; phase 2
SDGs
Other Subjects
avibactam plus ceftazidime; cefepime; antiinfective agent; avibactam, ceftazidime drug combination; azabicyclo derivative; ceftazidime; abdominal pain; acute pyelonephritis; adolescent; Article; child; clinical outcome; constipation; controlled study; coughing; cystitis; diarrhea; drug efficacy; drug safety; drug tolerability; Escherichia coli; female; fever; gastroenteritis; gastrointestinal disease; human; major clinical study; male; multicenter study; nausea; nephrolithiasis; neurologic disease; phase 2 clinical trial; priority journal; randomized controlled trial; rash; rhinopharyngitis; single blind procedure; treatment duration; treatment response; upper respiratory tract infection; urinary tract infection; vomiting; vulvitis; clinical trial; complication; drug combination; drug effect; infant; intravenous drug administration; microbiology; multidrug resistance; preschool child; urinary tract infection; Administration, Intravenous; Adolescent; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Child; Child, Preschool; Drug Combinations; Drug Resistance, Multiple, Bacterial; Escherichia coli; Female; Humans; Infant; Male; Single-Blind Method; Urinary Tract Infections
Publisher
Lippincott Williams and Wilkins
Type
journal article