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As part of our management protocol for preterm premature rupture of membranes, ceftizoxime and tocolysis were used to prolong the latent period and prevent or treat concomitant infection. Ceftizoxime was selected for this protocol based on its physiochemical properties, which favor placental transfer of the drug. Patients achieving steady-state pharmacodynamics (more than three doses of the drug) were considered eligible for study. Ceftizoxime levels were determined by reverse-phase high-pressure liquid chromatography. All levels measured after the first hour of treatment were indicative of the relative concentration of ceftizoxime in the fetal and amniotic fluid compartments when compared with the maternal compartment. Mean (±SEM) ceftizoxime levels were 11.96 + 2.35 μg/ml in maternal serum, 24.54 ± 4.78 μg/ml in cord serum, and 43.45 ± 4.97 μg/ml in amniotic fluid. Based on its broad antibacterial activity and its high concentration in fetal blood and amniotic fluid, ceftizoxime appears to be an ideal agent for treatment of the intrauterine environment.