Ampicillin and penicillin concentration in serum and pleural fluid of hospitalized children with community-acquired pneumonia.

Abstract

Optimal therapeutic efficacy of beta-lactam antibiotics for treatment of pneumococcal pneumonia is thought to be associated with the serum concentration greater than the minimum inhibitory concentration for 40-50% of the interdose interval at site of infection. Establish whether intravenous administration of ampicillin 400 mg/kg/day or penicillin 200,000 IU/kg/day in 6 divided doses reaches serum and or pleural concentrations above 4 microg/ml for at least 40% of the interdose interval. Hospitalized healthy children 1 month-14 years old with community-acquired bacterial pneumonia and empyema were eligible. Blood samples were obtained 30 min (C1) and 3 h (C2) after an antibiotic dose. Pleural fluid samples were obtained 1 and 4 h after the same dose in which blood samples were obtained. The concentrations were measured by high performance liquid chromatography. The study included 17 patients treated with ampicillin and 13 treated with penicillin. For ampicillin, mean serum concentrations were C1 37.3 +/- 19 microg/ml and C2 11 +/- 10.2 microg/ml and mean pleural fluid concentrations were C1 25.8 +/- 9.9 microg/ml and C2 16.2 +/- 7.9 microg/ml. For penicillin, mean serum concentrations were C1 21.8 +/- 16.4 microg/ml and C2 23.9 +/- 3.4 microg/ml. Mean pleural fluid concentrations were C1 10.9 +/- 2.2 microg/ml and C2 7.7 +/- 3.4 microg/ml. In 8 of 30 patients, serum C2 was <4 microg/ml; in all of them serum concentrations were >4 microg/ml for >40% of the interdose interval. This study of the pharmacokinetics of beta-lactam antibiotics in children with bacterial pneumonia may help in the development of therapeutic guidelines for the treatment of pneumococcal pneumonia.