Study on the therapeutic effect of cefozopran on perinatal infection in pregnant women

Abstract

An investigation was carried out to determine the therapeutic effect of cefozopran (CZOP), a injectable cephem antibiotics on infections in pregnant women during the perinatal period. Of the 78 patients enrolled in the study, 66 were subjected to the analysis, with 3 of the subjects having been exclnded because being pregnant for less than 16 weeks, 4 because of protocol violations (regimen), and 5 because of uncertain eridence symptoms of infection or failure to undergo laboratory tests. CZOP was administered by intravenous drip infusion at doses of 0.5 to 2 g twice daily for periods of 3 to 14 days. The efficacy rate according to the evaluation of the Drug Efficacy Evaluation Committee was 83.9%(47/56). The efficacy rate in the 37 patients from whom causative pathogens were isolated was 81.1%(30/37). The bacteriological effect of CZOP could be evaluated in 30 patients. The eradication rate was 80.0%(24/30), with 42 of the 49 clinical isolates (85.7%) being eradicated. The efficacy rate determined by the attending physicians in 57 patients was 87.7%(50/57), and 81.6%(31/38) for the 38 patients from whom causative pathogens were isolated. The eradication rate was 80.6%(25/31) and 43 of the 50 clinical isolates (86.0%) were eradicated. Safety was evaluated as “safe” in 63 of the 66 assessable patients (95.5%). Moderate headache and nausea were experienced by 1 patient (1.5%) as adverse drug reactions, but the symptoms disappeared after the completion of treatment. Slight elevations of GOT, GPT, and LDH in laboratory tests were observed in one patient (1.5%), but these values returned to normal after the completion of treatment. When CZOP was administered by intravenous drip infusion in a dose of 1 g over 30 min. to pregnant women before parturition, maternal blood drug concentrations changed from 30.5-42.6μg/ml 1 hour after administration to 1.0-3.3βg/ml 6 hours after administration.Pharmacokinetic analysis in a two-compartment open model showed that the blood elimination half-life of CZOP was 1.4-5.6 hours. After intravenous administration of a 1 g dose. CZOP levels in the fetus, amniotic fluid, and breast milk were determined. The concentrations of drug in blod and tissue were determined 36 to 135 minutes after administration. The concentrations ranged from 17.4 to 74.6 βg/ml in maternal blood, from 9.0 to 21.7 βg/ml in umbilical cord blood, from 1.5 to 7.5 pglg, in the umbilical cord, from 6.0 to 27.2 βg/g in the placenta, from 8.3 to 30.6βg/g in the fetal membranes, and from 0.3 to 3.3 βg/ml in amniotic fluid. These results suggested that CZOP can be a useful drug in the treatment of bacterial infections occurring during the perinatal period. To firmly establish its safety, however, further studies are needed in larger populations.