CEFAZOLIN

Fetal Risk Summary

Cefazolin is a parenteral, semisynthetic cephalosporin antibiotic. Reproduction studies in mice, rats, and rabbits found no evidence of impaired fertility or fetal harm at doses up to 25 times the human dose (1).

Cefazolin crosses the placenta into the cord serum and amniotic fluid (2,3,4,5 and 6). In early pregnancy, distribution is limited to the body fluids and these concentrations are considerably lower than those found in the 2nd and 3rd trimesters (3). At term, 15–70 minutes after a 500-mg dose, cord serum levels range from 35 to 69% of maternal serum (4). The maximum concentration in amniotic fluid after 500 mg was 8 µg/mL at 2.5 hours (5). No data on the newborns were given. Following a 2-g IV dose to seven women between 23 and 32 weeks' gestation, the mean serum concentration of cefazolin in hydropic and nonhydropic fetuses was 18.04 and 21.02 µg/mL, respectively, providing evidence that the presence of hydrops did not significantly impair the transfer of the antibiotic (6).

Cephalosporins are usually considered safe to use during pregnancy. Cefazolin, 2 g IV every 8 hours, has been used in the treatment of pyelonephritis occurring in the second half of pregnancy (7). No adverse fetal outcomes attributable to the drug were observed.

Breast Feeding Summary

Cefazolin is excreted into breast milk in low concentrations. Following a 2-g IV dose, average milk levels ranged from 1.2 to 1.5 µg/mL over 4 hours (milk:plasma ratio 0.02) (8). When cefazolin was given as a 500-mg IM dose, one to three times daily, the drug was not detectable (5). Although these levels 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. The American Academy of Pediatrics considers cefazolin to be compatible with breast feeding (9).

References

1. Product information. Ancef. SmithKline Beecham Pharmaceuticals, 1997.
2. Dekel A, Elian I, Gibor Y, Goldman JA. Transplacental passage of cefazolin in the first trimester of pregnancy. Eur J Obstet Gynecol Reprod Biol 1980;10:303–7.
3. Bernard B, Barton L, Abate M, Ballard CA. Maternal-fetal transfer of cefazolin in the first twenty weeks of pregnancy. J Infect Dis 1977;136:377–82.
4. Cho N, Ito T, Saito T, et al. Clinical studies on cefazolin in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 1970;18:770–7.
5. von Kobyletzki D, Reither K, Gellen J, Kanyo A, Glocke M. Pharmacokinetic studies with cefazolin in obstetrics and gynecology. Infection 1974;2(Suppl):60–7.
6. Brown CEL, Christmas JT, Bawdon RE. Placental transfer of cefazolin and piperacillin in pregnancies remote from term complicated by Rh isoimmunization. Am J Obstet Gynecol 1990;163:938–43.
7. Sanchez-Ramos L, McAlpine KJ, Adair CD, Kaunitz AM, Delke I, Briones DK. Pyelonephritis in pregnancy: once-a-day ceftriaxone versus multiple doses of cefazolin. Am J Obstet Gynecol 1995;172:129–33.
8. Yoshioka H, Cho K, Takimato M, Maruyama S, Shimizu T. Transfer of cefazolin into human milk. J Pediatr 1979;94:151–2.
9. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.