Ana María Ferrari

Standard case management of pneumonia in hospitalized children in Uruguay, 1997 to 1998

Objective. To report the results of the use of antimicrobial guidelines for the management of children with community-acquired bacterial pneumonia. Methods. Admittance and discharge criteria and algorithms for diagnosis and treatment were established. The decision to treat with antibiotics was based on radiologic findings in pneumonia with pulmonary consolidation and left to the attending physician’s criteria in the remaining cases. The use of antibiotics was limited to penicillin and derivatives (ampicillin, amoxicillin) and macrolides. Results. Of the 1163 children treated as bacterial pneumonia, hospitalized in public and private health facilities in Montevideo from September, 1997, through September, 1998, standard case management was applied in 1082 (93%). Age distribution was: <1 month, 1%; between 1 and 11 months, 29%; between 1 and 5 years, 50%; >5 years, 20%. Chest radiography showed evidence of pulmonary consolidation in 843 children (73%). Bacteria were detected in blood culture and/or pleural fluid of 57 children (5%). In 51 the identified microorganism was Streptococcus pneumoniae, susceptible to penicillin in 30, intermediate in 6 and resistant in 5 (maximum MIC, 4 &mgr;g/ml); in 10 cases etiologic diagnosis was made by antigen detection. Empyema was present in 62 children (5.3%); 38 (3.27%) required treatment in an intensive care unit; and 5 (0.4%) died. Conclusions. Compliance with standard case management was highly satisfactory. Outcome of children treated with penicillin and derivatives was good, including children with empyema and pneumatocele and two patients with penicillin-resistant S. pneumoniae. At the present time S. pneumoniae resistant to penicillin is not an important problem in children with pneumonia in Uruguay. Surveillance of identified microorganisms and their antimicrobial susceptibility must continue.

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.

Phenobarbital Pharmacokinetics in Infants Using Saliva as a Biologic Fluid

Objective: To determine the pharmacokinetic parameters of phenobarbital in infants, using saliva as a biologic fluid, and to correlate the parameters obtained from saliva data with those obtained from plasma data. Design: A prospective, randomized study. Setting: Hospitalized patients at the Medical Center Pereira Rossell, a pediatric hospital in Montevideo, Uruguay. Patients: Sixteen infants with seizure disorders were included in the study. None of them was treated with other medications. Interventions: A direct intravenous loading dose of phenobarbital 10 mg/kg was administered, followed by a maintenance dosage of 5 mg/kg/d (once- or twice-daily dosing) given 12 hours after the loading dose. Main Outcome Measures: Saliva and plasma samples were obtained 6 and 12 hours after the loading dose and 3 days after the initiation of the maintenance dose (trough sample): the samples were analyzed by HPLC and the elimination half-life (t1/2), the volume of distribution (Vd), and the percentage of unbound drug in plasma (UDP) were calculated. Results: The t1/2 obtained from plasma and saliva data was 30 hours; the Vd was 0.73 L/kg from plasma data and 2.4 L/kg from saliva data; and the UDP was 75 percent. Trough concentrations showed no significant difference between treatments. Conclusions: Saliva is a useful biologic fluid to determine phenobarbital pharmacokinetic parameters, mainly in pediatric patients. Moreover, a single daily dose of phenobarbital is sufficient to obtain therapeutic concentrations.