Clinical pharmacokinetics of once daily iv bolus gentamicin in pediatric patients with severe pneumonia at KNH

Abstract

Treatment of pneumonia using antibiotics at the Kenyatta National Hospital (KNH) is guided by clinical context, severity assessment and epidemiological data as well as antibiotic resistance patterns. High dose extended interval administration of gentamicin is the accepted empirical treatment for suspected gram negative pneumonia in children at KNH. Due to its narrow therapeutic range there is a need for routine therapeutic drug monitoring (TDM) to optimise the clinical use of gentamicin. However, TDM is expensive and is not a common practice at KNH. Hence, and there are limited data on pharmacokinetics of gentamicin in African children that can be used to rationalize its dosing in this population of patients. This prospective study describes the pharmacokinetics following "‘once daily” bolus administration (6.93+/- 1.35 mg/kg/24 hr) to African children with severe pneumonia. Sixteen children were enrolled into the study after obtaining written informed consent from the parents/guardians. Venous blood samples were collected for bacteriological culture and determination of gentamicin concentrations. The median age and weight, respectively, were 35 months and 12 kgs. One blood culture was positive for Coagulase negative staphylococcus. There were two treatment failures (12.5%) and two cases of nephrotoxicity. Peak gentamicin concentrations ranged from 4.80 to 21.57 pg/mL, while troughs concentrations ranged from 1.07 pg/mL to below 0.27 pg/mL. Gentamicin was undetectable in one patient (7.7%) approximately 8 hours after the bolus administration. At approximately 12 hours post dose, 5 patients (38.5%) had undetectable levels of gentamicin. Just before the next dose, 13 patients (81.25%) Vlll had gentamicin concentrations < 2 pg/mL. The median elimination half life was 2.1 hr while the median volume of distribution was 0.49 L/Kg. In conclusion, although 87.5% of the children recovered, the efficacy and safety of once daily dosing in children needs to be explored further in a larger patient population.