Antibiotic (Cephalosporin)
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Compatible
PREGNANCY SUMMARY
No detectable teratogenic risk with cephalosporin antibiotics was found in a large 2001 study (see Cephalexin).
FETAL RISK SUMMARY
Ceftazidime is a parenteral, semisynthetic cephalosporin antibiotic. Reproduction studies in mice and rats found no evidence of impaired fertility or fetal harm at doses up to 40 times the human dose (1). Cephalosporins are usually considered safe to use during pregnancy.
Ceftazidime administered at various stages of gestation, including the 1st trimester, crosses the placenta to the fetus and appears in the amniotic fluid (2–4). A brief English abstract of a 1983 Japanese report stated that levels in the cord blood and amniotic fluid following a 1-g IV dose exceeded the minimum inhibitory concentrations for most causative organisms but did not give specific values (2).
Nine women, undergoing abortion for fetuses affected by β-thalassemia major between 19 and 21 weeks’ gestation, were given ceftazidime 1 g IM three times a day (3). At least three doses of the antibiotic were administered prior to abortion. The average concentrations of the drug in maternal serum at 2 and 4 hours after the last dose were 19.5 mcg/mL (range 14–25 mcg/mL) and 1.5 mcg/mL (range 1.4–1.6 mcg/mL), respectively. The simultaneous levels in amniotic fluid were 2.7 mcg/mL (range 1.3–4 mcg/mL) and 3.1 mcg/mL (range 2.2–3.9 mcg/mL), respectively, corresponding to approximately 14% and 207% of the maternal concentrations, respectively.
In a 1987 report, 30 women received a single 2-g IV bolus dose over 3 minutes of ceftazidime between 1 and 4 hours prior to undergoing abortion of a fetus at a mean gestational age of 10 weeks (range 7–12 weeks) (4). Antibiotic concentrations were determined in maternal plasma, placental tissue, and amniotic fluid. In maternal plasma, mean levels ranged from 76 mcg/mL at 1 hour to 16.5 mcg/mL at 4 hours. Placental tissue concentrations were constant over this time interval, 12 mg/kg at 1 hour and 13 mg/kg at 4 hours, whereas the amniotic fluid concentration increased from 0.5 to 2.8 mcg/mL, respectively.
Increased renal elimination of ceftazidime was found in 12 women with asymptomatic bacteriuria treated with a 400-mg bolus dose, followed by a continuous infusion of 1 g for 4 hours (5). The initial treatment occurred during the 1st trimester, followed by treatments approximately 2 weeks before delivery at term and after cessation of breastfeeding. The mean renal clearances of the antibiotic during the three administrations were 143, 170, and 103 mL/minute, respectively.
BREASTFEEDING SUMMARY
Low concentrations of ceftazidime are excreted into breast milk (6). Eleven women were treated with 2 g of ceftazidime IV every 8 hours for endometritis following cesarean section. No mention was made as to whether the women were breastfeeding during treatment. Plasma and milk samples were collected between 2 and 4 days of therapy (total number of doses received averaged 12.6). The mean maternal plasma levels of the antibiotic just prior to a dose and 1 hour after a dose were 7.6 and 71.8 mcg/mL, respectively. The mean concentrations in breast milk before a dose and at 1 and 3 hours after a dose were 3.8, 5.2, and 4.5 mcg/mL, respectively. No accumulation of the antibiotic in milk was observed.
Three potential problems exist for the nursing infant exposed to ceftazidime 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. The American Academy of Pediatrics classifies ceftazidime as compatible with breastfeeding (7).
References
1.Product information. Fortaz. Glaxo Wellcome, 1997.
2.Cho N, Suzuki H, Mitsukawa M, Tamura T, Yamaguchi Y, Maruyama M, Aoki K, Fukunaga K, Kuni K. Fundamental and clinical evaluation of ceftazidime in the field of obstetrics and gynecology (English abstract). Chemotherapy (Tokyo) 1983;31(Suppl 3):772–82.
3.Giamarellou H, Gazis J, Petrikkos G, Antsaklis A, Aravantinos D, Daikos GK. A study of cefoxitin, moxalactam, and ceftazidime kinetics in pregnancy. Am J Obstet Gynecol 1983;147:914–9.
4.Jørgensen NP, Walstad RA, Molne K. The concentrations of ceftazidime and thiopental in maternal plasma, placental tissue and amniotic fluid in early pregnancy. Acta Obstet Gynecol Scand 1987;66:29–33.
5.Nathorst-Boos J, Philipson A, Hedman A, Arvisson A. Renal elimination of ceftazidime during pregnancy. Am J Obstet Gynecol 1995;172:163–6.
6.Blanco JD, Jorgensen JH, Castaneda YS, Crawford SA. Ceftazidime levels in human breast milk. Antimicrob Agents Chemother 1983;23:479–80.
7.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.