Clinical and pharmacological evaluation of a modified cefotaxime bid regimen versus traditional tid in pediatric lower respiratory tract infections.

It is generally accepted that the treatment of community-acquired pneumonia, either in adults or in pediatric patients, is mainly empirical. Thus, the treatment selection must fulfill both the epidemiological requirements, according to the most frequently described pathogens, and the pharmacological criteria to ensure adequate and prolonged drug concentrations at the infection site, to reach clinical efficacy. Cefotaxime has proven to be effective in this indication when traditionally administered three times daily and, more recently, twice daily, as a result of a re-evaluation of its pharmacokinetic/pharmacodynamic features. To gain further evidence using this updated dosing schedule, 258 pediatric patients with lower respiratory tract infections were treated with cefotaxime 100 mg/kg/day, administered as a twice daily or three times daily regimen. In the cefotaxime 50 mg/kg twice-daily group (n = 130), a complete resolution of clinical signs and symptoms were observed in 88.5% of patients. Similarly, in the cefotaxime 33.3 mg/kg group (n = 128), 93.6% of patients had a complete resolution of clinical signs and symptoms. Both drug schedules were well tolerated. Pharmacokinetic parameters determined for the two cefotaxime dosing schedules showed comparability. The serum half-life of desacetylcefotaxime was marginally longer than for cefotaxime in both dosage groups (1.64 and 1.36 h for desacetylcefotaxime versus 1.2 and 0.85 h for cefotaxime after 50 mg/kg or 33.3 mg/kg doses, respectively). Results from this study support the use of twice-daily cefotaxime administration for the treatment of lower respiratory tract infections in pediatric patients.

Aztreonam in the treatment of severe urinary tract infections in pediatric patients.

Aztreonam was administered to 30 patients, ages 0.03 to 15.4 years, with severe and in 21 cases complicated urinary tract infections caused by members of the family Enterobacteriaceae and Pseudomonas aeruginosa which were resistant to ampicillin and susceptible to the study drug in vitro. A mean dose of 47.7 mg/kg was given intramuscularly every 12 h to 26 patients. In four patients with renal insufficiency, the dose was reduced according to pharmacokinetic data. Permanent urine sterilization and clinical cure were achieved in 22 patients, 13 of whom had urological malformations. In two patients with P. aeruginosa and Proteus mirabilis infections, the treatment failed. Another patient had an Escherichia coli reinfection 21 days after the end of therapy. Four patients with various urological abnormalities had gram-positive superinfections, and two patients had gram-negative superinfections during and at the end of therapy: all six had indwelling ureteric splints or pyelostomy as predisposing conditions. No adverse clinical effects were observed. Some transient and slight or moderate alterations were observed at the end of treatment: eosinophilia (nine cases), elevation of hepatic enzymes (eight cases), prolongation of prothrombin time (three cases), and neutropenia (one case). A pharmacokinetic study was performed in six patients with normal renal function and in seven patients with various degrees of renal insufficiency. The elimination half-life of the drug was inversely correlated with the glomerular filtration rate. At the dosage used, aztreonam proved effective for severe urinary tract infections caused by members of the family Enterobacteriaceae in pediatric patients.