Cefuroxime

 Risk Factor: BM
 Class: ANTI-INFECTIVES / Cephalosporins

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Cefuroxime is an oral and parenteral, semisynthetic cephalosporin antibiotic. Reproduction studies in rats have found no evidence of impaired fertility at doses up to 9 times the maximum recommended human dose on a mg/m2 basis (MRHD) or, mice and rats, of fetal harm at doses up to 23 times the MRHD (1).

Cefuroxime readily crosses the placenta in late pregnancy and labor, achieving therapeutic concentrations in fetal serum and amniotic fluid (2,3,4,5,6 and 7). Therapeutic antibiotic levels in infants can be demonstrated up to 6 hours after birth with measurable concentrations persisting for 26 hours. The pharmacokinetics of cefuroxime in pregnancy have been reported (8). The antibiotic has been used for the treatment of pyelonephritis in pregnancy (9). Adverse effects in the newborn after in utero exposure have not been observed. Cephalosporins are usually considered safe to use during pregnancy.

In women at 1535 weeks' gestation, a single 750-mg IV dose produced mean serum concentrations in mothers, hydropic fetuses, and fetuses with oligohydramnios of 7.4, 6.2, and 4.9 g/mL, respectively (10). The concentrations did not correlate with gestational age. Nine women with premature rupture of the membranes at 2733 weeks' gestation received 1.5 g IV of cefuroxime three times daily (11). The mean concentrations of the antibiotic in the mothers (1 hour after a dose), umbilical cord plasma, placenta, and membranes were 35.0 g/mL, 3.0 g/mL, 11.2 g/g, and 35.6 g/g, respectively.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 143 newborns had been exposed to cefuroxime during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Three (2.1%) major birth defects were observed (six expected), but no anomalies were observed in six categories of defects for which specific data were available (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias). These data do not support an association between the drug and congenital defects (see also Cefaclor, Cephalexin, and Cephradine for contrasting results).

The pregnancy outcomes of 106 women exposed in the 1st trimester to cefuroxime were described in a 2000 study (12). Compared to 106 matched controls, there was no difference in pregnancy outcomes in terms of live births, spontaneous abortions, gestational age at birth, prematurity, birth weight, fetal distress, method of delivery, and major or minor malformations. Induced abortions, however, occurred in significantly more cefuroxime-exposed women then controls, possibly due to misinformation and misperception of the risk the antibiotic posed to a pregnancy (12).

Breast Feeding Summary

Cefuroxime is excreted into breast milk in low concentrations (1), but published data have not been located. Even though the levels are low, three potential problems exist for the nursing infant exposed to cefuroxime in milk: 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 cefuroxime, the American Academy of Pediatrics classifies other cephalosporin antibiotics as compatible with breast feeding (13).

References

1. Product information. Ceftin. Glaxo Wellcome, 1997.
2. Craft I, Mullinger BM, Kennedy MRK. Placental transfer of cefuroxime. Br J Obstet Gynaecol 1981;88:1415.
3. Bousfield P, Browning AK, Mullinger BM, Elstein M. Cefuroxime: potential use in pregnant women at term. Br J Obstet Gynaecol 1981;88:1469.
4. Bergogne-Berezin E, Pierre J, Even P, Rouvillois JL, Dumez Y. Study of penetration of cefuroxime into bronchial secretions and of its placental transfer. Therapie 1980;35:67784.
5. Tzingounis V, Makris N, Zolotas J, Michalas S, Aravantinos D. Cefuroxime prophylaxis in caesarean section. Pharmatherapeutica 1982;3:1402.
6. Coppi G, Berti MA, Chehade A, Franchi I, Magro B. A study of the transplacental transfer of cefuroxime in humans. Curr Ther Res 1982;32:7126.
7. Bousefield PF. Use of cefuroxime in pregnant women at term. Res Clin Forums 1984;6:538.
8. Philipson A, Stiernstedt G. Pharmacokinetics of cefuroxime in pregnancy. Am J Obstet Gynecol 1982;142:8238.
9. Faro S, Pastorek JG II, Plauche WC, Korndorffer FA, Aldridge KE. Short-course parenteral antibiotic therapy for pyelonephritis in pregnancy. S Med J 1984;77:4557.
10. Holt DE, Fisk NM, Spencer JAD, de Louvlis J, Hurley R, Harvey D. Transplacental transfer of cefuroxime in uncomplicated pregnancies and those complicated by hydrops or changes in amniotic fluid volume. Arch Dis Child 1993;68:547.
11. De Leeuw JW, Roumen FJME, Bouckaert PXJM, Cremers HMHG, Vree TB. Achievement of therapeutic concentrations of cefuroxime in early preterm gestations with premature rupture of the membranes. Obstet Gynecol 1993;81:25560.
12. Berkovitch M, Segal-Socher I, Greenberg R, Bulkowshtein M, Arnon J, Perlob P, Or-Noy A. First trimester exposure to cefuroxime: a prospective chort study. Br J Clin Pharmacol 2000;50:1615.
13. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.