Subject(s)
Delivery of Health Care/economics , Health Promotion/organization & administration , Health Services Accessibility/economics , Health Status , Population Dynamics , Quality Indicators, Health Care/statistics & numerical data , Humans , National Health Programs/economics , Poverty/statistics & numerical data , Social Change , Social Responsibility , Socioeconomic Factors , South AfricaSubject(s)
Anti-Bacterial Agents/supply & distribution , Bacterial Infections/drug therapy , Drug Resistance, Bacterial , Health Promotion/organization & administration , Health Status , Prescription Drugs/supply & distribution , Anti-Bacterial Agents/economics , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/epidemiology , Drug Costs/statistics & numerical data , Humans , National Health Programs/organization & administration , Prescription Drugs/economics , Prescription Drugs/therapeutic use , South AfricaABSTRACT
OBJECTIVE: To determine the pharmacokinetic profile of ciprofloxacin 20 mg/kg per day (10 mg/kg administered intravenously 12 hourly) in paediatric patients with severe sepsis. DESIGN: Open and prospective. SETTING: Tertiary referral multi-disciplinary ICU. PATIENTS: Twenty patients (two groups - group A: 3 months-1 year; group B 1-5 years). INTERVENTIONS: Timed blood samples were taken for pharmacokinetics after the first dose (D(0)), as well as day 2 (D(2)) and then between days 6-8. MEASUREMENTS AND RESULTS: Ciprofloxacin serum levels were measured by high performance liquid chromatography. Demographic and clinical data and all adverse events were noted. Standard pharmacokinetic variables were calculated by non-compartmental methods. Peak concentrations (C(max)) for group A were D(0) 6.1+/-1.2 mg/l, D(2) 9.0+/-1.8 mg/l and D(7) 5.8+/-1.3 mg/l and, for group B, 7.4+/-1.3 mg/l, 7.8+/-1.6 mg/l and 6.4+/-1.3 mg/l, respectively, for the study periods. Concentration 12 h after the start of infusion (C(min)) for all periods were 0.2 mg/l or less. Areas under the curve (AUC, 12 h) were group A: 15.6+/-1.3, 19.2+/-1.63 and 14.1+/-1.4 mg/h per l, and group B: 15.9+/-1.3, 18.0+/-1.7 and 13.2+/-1.26 mg/h per l. One patient presenting with seizures, initially controlled, had another convulsion and a further patient developed seizures whilst on ciprofloxacin. C(max) in these patients were higher than the average C(max). The convulsions of both patients were easily controlled. No other drug-related serious adverse events occurred. No arthropathy was noted. Three patients died of their underlying disease. CONCLUSIONS: There was no accumulation of drug even after 7 days of administration. Our C(max) and AUC were lower than that achieved in a similar adult pharmacokinetic study. To achieve end points of area under the inhibitory curve (AUIC) of 100-150 mg/h per l, 10 mg/kg ciprofloxacin eight hourly would be required for some resistant ICU organisms.
