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

Background: Optimal therapeutic efficacy of β-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. Objective: 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 μg/ml for at least 40% of the interdose interval. Materials and Methods: 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. Results: The study included 17 patients treated with ampicillin and 13 treated with penicillin. For ampicillin, mean serum concentrations were C1 37.3 ± 19 μg/ml and C2 11 ± 10.2 μg/ml and mean pleural fluid concentrations were C1 25.8 ± 9.9 μg/ml and C2 16.2 ± 7.9 μg/ml. For penicillin, mean serum concentrations were C1 21.8 ± 16.4 μg/ml and C2 23.9 ± 3.4 μg/ml. Mean pleural fluid concentrations were C1 10.9 ± 2.2 μg/ml and C2 7.7 ± 3.4 μg/ml. In 8 of 30 patients, serum C2 was <4 μg/ml; in all of them serum concentrations were >4 μg/ml for >40% of the interdose interval. Conclusions: This study of the pharmacokinetics of β-lactam antibiotics in children with bacterial pneumonia may help in the development of therapeutic guidelines for the treatment of pneumococcal pneumonia.