CEFOPERAZONE

Fetal Risk Summary

Cefoperazone is a parenteral, semisynthetic cephalosporin antibiotic. Reproduction studies in mice, rats, and monkeys have found no evidence of impaired fertility, reproductive performance, or fetal harm at doses up to 10–20 times the human dose (1).

Following a 1-g IV or IM dose of cefoperazone, cord blood levels averaged 34.4 and 33.2%, respectively, of the maternal serum (2). Peak concentrations occurred at about 1 hour after both IV and IM doses. Amniotic fluid levels were 3–4 µg/mL within 6 hours of administration. Continuous IV dosing (1 g given two to four times every 12 hours) produced higher levels with cord blood averaging 40%–48% of maternal serum and amniotic fluid levels increasing to 3.8–8.8 µg/mL. In a second study, 1 g IV produced peak cord blood concentrations averaging about 45% of maternal serum (25 µg/mL vs. 56.1 µg/mL) at 70 minutes with amniotic fluid concentrations varying between 2.8 and 4.8 µg/mL at 180 minutes (3). No effects on the newborns were reported in either study. In an in vitro experiment, placental transfer of cefoperazone was shown to occur only by simple diffusion (4). Cephalosporins are usually considered safe to use during pregnancy.

The placental transfer of cefoperazone and ceftizoxime were studied in an in vitro perfused human placental system (5). The mean clearance indices for the two antibiotics were 0.037 and 0.126, respectively. The steady-state fetal concentrations of the two agents were 4 µg/mL and 4–5 µg/mL, respectively.

Breast Feeding Summary

Cefoperazone is excreted into breast milk in low concentrations. An IV dose of 1 g produced milk levels ranging from 0.4 to 0.9 µg/mL (C.E. Jacobson, personal communication, Roerig, 1985). Even though these concentrations are low, three potential problems exist for the nursing infant: modification of bowel flora, direct effects on the infant, and interference with the interpretation of culture results if a fever workup is required. Although not specifically listing cefoperazone, the American Academy of Pediatrics classifies other cephalosporin antibiotics as compatible with breast feeding (6).

References

1. Product information. Cefobid. Pfizer, 1997.
2. Matsuda S, Tanno M, Kashiwagura T, Furuya H. Placental transfer of cefoperazone (T-1551) and a clinical study of its use in obstetrics and gynecological infections. Curr Chemo Infect Dis 1979;2:167–8.
3. Shimizu K. Cefoperazone: absorption, excretion, distribution, and metabolism. Clin Ther 1980;3(Special Issue):60–79.
4. Fortunato SJ, Bawdon RE, Baum M. Placental transfer of cefoperazone and sulbactam in the isolated in vitro perfused human placenta. Am J Obstet Gynecol 1988;159:1002–6.
5. Fortunato SJ, Bawdon RE, Maberry MC, Swan KF. Transfer of ceftizoxime surpasses that of cefoperazone by the isolated human placental perfused in vitro. Obstet Gynecol 1990;75:830–3.
6. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.