Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial
Language English Country United States Media print
Document type Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
31306396
DOI
10.1097/inf.0000000000002392
PII: 00006454-201908000-00010
Knihovny.cz E-resources
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Azabicyclo Compounds administration & dosage adverse effects pharmacokinetics therapeutic use MeSH
- Ceftazidime administration & dosage adverse effects pharmacokinetics therapeutic use MeSH
- Child MeSH
- Drug Combinations MeSH
- Infant MeSH
- Drug Therapy, Combination MeSH
- Combined Modality Therapy MeSH
- Humans MeSH
- Metronidazole administration & dosage adverse effects pharmacokinetics therapeutic use MeSH
- Microbial Sensitivity Tests MeSH
- Adolescent MeSH
- Drug Resistance, Multiple, Bacterial MeSH
- Intraabdominal Infections diagnosis drug therapy microbiology MeSH
- Postoperative Complications * MeSH
- Child, Preschool MeSH
- Age Factors MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- avibactam, ceftazidime drug combination MeSH Browser
- Azabicyclo Compounds MeSH
- Ceftazidime MeSH
- Drug Combinations MeSH
- Metronidazole MeSH
BACKGROUND: Ceftazidime-avibactam plus metronidazole is effective in the treatment of complicated intra-abdominal infection (cIAI) in adults. This single-blind, randomized, multicenter, phase 2 study (NCT02475733) evaluated the safety, efficacy and pharmacokinetics of ceftazidime-avibactam plus metronidazole in children with cIAI. METHODS: Hospitalized children (≥3 months to <18 years) with cIAI were randomized 3:1 to receive intravenous ceftazidime-avibactam plus metronidazole, or meropenem, for a minimum of 72 hours (9 doses), with optional switch to oral therapy thereafter for a total treatment duration of 7-15 days. Safety and tolerability were assessed throughout the study, along with clinical and microbiologic outcomes, and pharmacokinetics. A blinded observer determined adverse event (AE) causality, and clinical outcomes up to the late follow-up visit. RESULTS: Eighty-three children were randomized and received study drug (61 ceftazidime-avibactam plus metronidazole and 22 meropenem); most (90.4%) had a diagnosis of appendicitis. Predominant Gram-negative baseline pathogens were Escherichia coli (79.7%) and Pseudomonas aeruginosa (33.3%); 2 E. coli isolates were ceftazidime-non-susceptible. AEs occurred in 52.5% and 59.1% of patients in the ceftazidime-avibactam plus metronidazole and meropenem groups, respectively. Serious AEs occurred in 8.2% and 4.5% of patients, respectively; none was considered drug related. No deaths occurred. Favorable clinical/microbiologic responses were observed in ≥90% of patients in both treatment groups at end-of-intravenous treatment and test-of-cure visits. CONCLUSIONS: Ceftazidime-avibactam plus metronidazole was well tolerated, with a safety profile similar to ceftazidime alone, and appeared effective in pediatric patients with cIAI due to Gram-negative pathogens, including ceftazidime-non-susceptible strains.
AstraZeneca Alderley Park Macclesfield United Kingdom
From the Rady Children's Hospital University of California San Diego School of Medicine San Diego CA
Hospital Universitari Germans Trias i Pujol Barcelona Spain
Pfizer Sandwich Kent United Kingdom
References provided by Crossref.org
ClinicalTrials.gov
NCT02475733
