Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients

Abstract

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0–∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016

“…Ceftazidime-avibactam was approved by the U.S. Food and Drug Administration (FDA) and by the European Medicine Agency (EMA) to treat complicated intraabdominal infection in combination with metronidazole, as well as complicated urinary tract infections, including pyelonephritis (17,18). Ceftazidime-avibactam is also approved to treat nosocomial pneumonia in Europe and has been studied in pediatric patients (NCT01893346) (19). As part of the International Network for Optimal Resistance Monitoring (INFORM) surveillance program, we evaluated the activity of ceftazidime-avibactam against a large collection of contemporary (2013 to 2016) MDR Gram-negative organisms causing infections in patients from U.S. medical centers.…”

Assessment of 30/20-Microgram Disk Content versus MIC Results for Ceftazidime-Avibactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa

“…Ceftazidime-avibactam is also approved to treat nosocomial pneumonia in Europe and has been studied in pediatric patients (ClinicalTrials.gov registration no. NCT01893346) (8).…”

Review of Clinical Pharmacokinetics of Avibactam, A Newly Approved non-β lactam β-lactamase Inhibitor Drug, In Combination Use With Ceftazidime

“…Judging by the limited data available in pediatric patients [33], the pharmacokinetics of avibactam appeared to be comparable to the data obtained in healthy volunteers for key parameters such as total body clearance and volume of distribution ▶ table 2.…”