This collaborative work by researchers from Brazil, Finland, and the World Health Organization investigated the pharmacokinetics (PK) of amoxicillin thrice versus twice a day in children 3 months to <6 years of age with nonsevere pneumonia presenting to the Albert Sabin Children’s Hospital of Fortaleza, Brazil. Nonsevere pneumonia was defined as cough or difficult breathing and tachypnea without retractions or other severe signs (eg, cyanosis, obtundation). Patients with other severe underlying conditions or receipt of amoxicillin 48 hours prior, and those requiring parenteral antibiotic therapy were excluded from the study. Eighty children were enrolled in the study and randomized to amoxicillin 15 mg/kg/dose 3 times a day (tid) or 25 mg/kg/dose 2 times a day (bid). The 2 study groups did not differ in demographic and clinical variables. Seven children from each group were excluded because of incomplete blood sampling. The remaining 66 children form the basis of this report. Pharmacokinetic (PK) samples were drawn prior to the first dose and 2, 5, and 8 hours after the first dose on days 1 and 3, and for the bid group 12 hours after dose on these 2 days. The area under the blood drug concentration (AUC) was compared on days 1 and 3. The percentage of dose interval for which the concentration exceeded the minimal inhibitory concentration (MIC)1 of 0.5, 1 and 2 μg/ml was calculated, as they are commonly used break points for Streptococcus pneumoniae.
The plasma amoxicillin concentrations in general, maximum concentrations, and AUC were higher for the bid group. Concentrations on day 1 and 3 were comparable and age of children had no effect on PK variables. However, the mean percentage of dose interval for which the concentration remained above each of the 3 MIC levels was higher in the 15 mg/kg tid group compared to the 25 mg/kg bid group. For example, the percentage of children in whom the concentration of amoxicillin remained below an MIC of 2 μg/ml for more than half the dose interval was 59% at day 1 for the bid group and 42% for the tid group, and on day 3, 58% for the bid group and 26% for the tid group (Fisher’s P=.02).
Fewer doses of medications are very likely to increase adherence to an antibiotic regimen, which, in turn, decreases treatment failures, development of resistance and overall cost of treatment.2 (See also