Bacteriological and clinical effect of a newly developed SBT/CPZ in the treatment for pediatric patients was assessed by a study group consisting of 15 institutions. The results were as follows.
1. Antibacterial effect
Susceptibility studies were performed with 93 clinical isolates. The MIC of SBT/CPZ was one-tube inferior or almost similar to that of CPZ in susceptible organisms. In CPZ-resistant organisms at the inoculum of 10
8 cells/ml, however, SBT/CPZ was much superior to CPZ on the basis of the MIC.
When the MIC of SBT/CPZ was compared to that of CPZ in 27 strains which have high β-lactamase-producing activity, it was found that many of CPZ-resistant organisms were susceptible to SBT/CPZ.
2. Serum concentration and urinary excretion
The serum concentrations of SBT and CPZ were 33.2 μg/ml and 79.2 μg/mI, respectively at 15 minutes after 20 mg/kg SBT/CPZ was administered by intravenous bolus injection, and those of SBT and CPZ, 51.0 μg/ml and 108.3 μg/ml, respectively following 40 mg/kg SBT/CPZ therapy. The serum concentrations of CPZ were 2.1-2.4 times as high as those of SBT. The concentrations were dose-related. The half-lives of SBT and CPZ following 20 mg/kg SBT/CPZ administration were 0.94 hour and 1.50 hours, respectively, and those following 40 mg/kg SBT/CPZ were 0.95 hour and 1.53 hours, respectively. There was no significant difference between 20 mg/kg and 40 mg/kg administrations. When compared between SBT and CPZ, CPZ had slightly longer half-lives.
At the termination of 1 hour drip infusion of 20 mg/kg SBT/CPZ, the serum concentrations of SBT and CPZ were 16.7 μg/ml and 40.1 μg/ml, respectively. In the case of 40 mg/kg, the levels of SBT and CPZ were 38.6 μg/ml and 94.9 μg/ml, respectively. The concentrations were found to be dose-related as were following intravenous bolus injections. The SBT half-lives obtained after 20 mg/kg and 40 mg/kg SBT/CPZ administrations were 1.39 hours and 0.89 hour, respectively; those of CPZ, 2.00 hours and 1.44 hours, respectively.
The highest urinary concentration occurred 0-2 hours after intravenous bolus injections of 20 mg/kg or 40 mg/kg SBT/CPZ. Urinary excretion of SBT over 6 hours was 60.0% and 67.7%, and that of CPZ, 21.2% and 25.0%, indicating higher urinary excretion for SBT.
When 20 mg/kg SBT/CPZ or 40 mg/kg was administered over 1 hour by drip infusion, urinary excretion became the highest at 1-3 hours after administration. Urinary excretion of SBT over 7 hours following 20 mg/kg and 40 mg/kg SBT/CPZ was 68.8% and 80.3%, respectively, and that of CPZ, 24.4% and 27.3%. The results were similar to those observed following intravenous bolus injections.
3. Clinical results
Out of a total of 286, 264 patients were assessed on clinical efficacy. Twenty-two patients were dropouts or excluded.
The clinical efficacy was excellent or good in 148 out of 156 patients in whom causative organisms were isolated, with the efficacy rate of 94.9%. The efficacy rate in 108 patients in whom causative organisms were not detected was 91.7% which was not significantly different from that in the former group. The total efficacy rate was 93.6%; excellent or good in 247 out of 264 patients.
In bacteriological studies, 166 out of 174 causative strains were eradicated with the eradication rate of 95.4%. Out of 27 β-lactamase producing strains, 25 were eradicated. The eradication rate was 92.6%.
The clinical efficacy was excellent or good in 40 patients out of 44 who had not responded to other antibiotics. The efficacy rate was 90.9%.
4. Side effects and laboratory tests
Out of a total of 286 patients, 279 were examined on side effects and laboratory-test abnormality. Seven patients were excluded from the assessment because they had failed to follow the predetermined administration schedule. The side effects observed were fever, rash, soft stool and diarrhea.
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