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.)
Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI). Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms. Methods. Patients (n = 31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared. Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp., P < .0001 for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE. Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.
Purpose: Physical activity is well known to improve or maintain exercise capacity and overall health in patients with cystic fibrosis (CF). However, many patients do not meet recommended guidelines for physical activity. The purpose of this study was to determine if individualized, targeted coaching could improve the levels of physical activity and quality of life in children and adolescents with CF. Subjects: Twelve children with CF, ages 7 to 17, participated in this study.Method: Each participant completed a physical activity questionnaire (PAQ) and a disease-specific quality of life questionnaire (CFQ) at baseline and three months later. The participants were given pedometers and a 10,000 step per day target. Participants also participated in discussions regarding ways to increase physical activity appropriate for their interest, abilities and age. Weekly follow-up phone calls were made to obtain pedometer counts and discuss physical activities performed. Results: Physical activity scores (PAQ) improved in 6 of 12 participants. Quality of life improved in many dimensions of the CFQ, particularly in vitality (3 of 5 improved); emotional (8 of 12 improved) and respiratory (7 of 12 improved). Conclusions: The results of this small pilot study suggest that an individualized coaching approach to physical activity in children and adolescents with CF may improve physical activity levels and improve important aspects of quality of life in some children with CF.
A token economy effectively increased exercise in children with CF, and the single-subject design highlighted some of the intricacies of individualized treatment of adherence. Implications and recommendations for further research are discussed.
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