CEFTIZOXIME

Fetal Risk Summary

Ceftizoxime is a parenteral, semisynthetic cephalosporin antibiotic. Reproduction studies in rats found no evidence of impaired fertility at doses up to approximately two times the maximum human daily dose on a mg/m2 basis or, in rats and rabbits, of fetal harm (1).

The placental transfer of ceftizoxime and cefoperazone were studied in an in vitro perfused human placental system (2). The mean clearance indices for the two antibiotics were 0.126 and 0.037, respectively. The steady state fetal concentrations of the two agents were 4–5 µg/mL and 4 µg/mL, respectively.

Following 1- or 2-g IV doses administered to women at term, peak cord blood levels occurred at 1–2 hours with concentrations ranging between 12 and 30 µg/mL (3,4,5,6 and 7). Amniotic fluid concentrations were lower with peak levels of 10–20 µg/mL at 2–3 hours. The mean fetal:maternal ratio reported in one group of patients after a 2-g IV dose was 0.28 (7). In a different study, maternal, fetal, and amniotic concentrations were measured in women who had received at least three doses of ceftizoxime 2 g at 8-hour intervals (8). Mean levels at delivery in the various compartments were 11.96, 24.54, and 43.45 µg/mL, respectively. Cord blood levels averaged 1.6 times higher than maternal levels with average amniotic fluid concentrations 2.9 times those in the maternal serum (8). No adverse fetal or newborn effects were noted in any of the trials.

A 1993 report found that protein binding of ceftizoxime was significantly less in fetal blood than in maternal blood (9). The mean binding to fetal proteins was 21.9% compared with maternal protein binding of 57.8%.

An abstract of a multicenter, double-blind, randomized study published in 1993 found no difference between ceftizoxime (2 g IV every 8 hours) (N=154) and placebo (N=152) in the percentage of women with preterm premature rupture of the membranes who were undelivered at 7 days (10). Only noninfected women who were not in labor were enrolled in the study. A prospective, double-blind, placebo-controlled study published in 1995 found that ceftizoxime (2 g IV every 8 hours) had no effect on the interval to delivery or duration of pregnancy in women, with intact membranes and without chorioamnionitis, who were in preterm (<37 weeks' gestation) labor (11).

No fetal or newborn adverse effects following exposure to ceftizoxime during pregnancy have been reported. Cephalosporins are usually considered safe to use during pregnancy.

Breast Feeding Summary

Ceftizoxime is excreted into breast milk in low concentrations (7,12). Mean levels following single doses of 1 and 2 g were less than 0.5 µg/mL. Even though 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. Although not specifically listing ceftizoxime, the American Academy of Pediatrics classifies other cephalosporin antibiotics as compatible with breast feeding (13).

References

1. Product information. Cefizox. Fujisawa USA, 1997.
2. 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.
3. Cho N, Fukunaga K, Kunii K. Studies on ceftizoxime (CZX) in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 1980;28(Suppl 5):821–30.
4. Matsuda S, Seida A. Clinical use of ceftizoxime in obstetrics and gynecology. Chemotherapy (Tokyo) 1980;28(Suppl 5):812–20.
5. Okada E, Kawada A, Shirakawa N. Clinical studies on transplacental diffusion of ceftizoxime into fetal blood and treatment of infections in obstetrics and gynecology. Chemotherapy (Tokyo) 1980;28(Suppl 5):874–87.
6. Seiga K, Minagawa M, Egawa J, Yamaji K, Sugiyama Y. Clinical and laboratory studies on ceftizoxime (CZX) in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 1980;28(Suppl 5):845–62.
7. Motomura R, Kohno M, Mori H, Yamabe T. Basic and clinical studies of ceftizoxime in obstetrics and gynecology. Chemotherapy (Tokyo) 1980;28(Suppl 5):888–99.
8. Fortunato SJ, Bawdon RE, Welt SI, Swan KF. Steady-state cord and amniotic fluid ceftizoxime levels continuously surpass maternal levels. Am J Obstet Gynecol 1988;159:570–3.
9. Fortunato SJ, Welt SI, Stewart JT. Differential protein binding of ceftizoxime in cord versus maternal serum. Am J Obstet Gynecol 1993;168:914–5.
10. Blanco J, Iams J, Artal R, Baker D, Hibbard J, McGregor J, Cetrulo C. Multicenter double-blind prospective random trial of ceftizoxime vs placebo in women with preterm premature ruptured membranes (PPROM). Am J Obstet Gynecol 1993;168:378.
11. Gordon M, Samuels P, Shubert P, Johnson F, Gebauer C, Iams J. A randomized, prospective study of adjunctive ceftizoxime in preterm labor. Am J Obstet Gynecol 1995;172:1546–52.
12. Gerding DN, Peterson LR. Comparative tissue and extravascular fluid concentrations of ceftizoxime. J Antimicrob Chemother 1982;10(Suppl C):105–16.
13. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.