Antibiotic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Compatible
PREGNANCY SUMMARY
No reports describing the therapeutic use of aztreonam in human pregnancy have been located. However, several studies have found that the drug crosses the human placenta and have described the pharmacokinetics in pregnancy. The animal reproduction data suggest low risk, but the absence of therapeutic experience in pregnancy prevents a more complete assessment of the embryo–fetal risk. Nevertheless, if the drug is indicated, it should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Aztreonam is a synthetic, monocyclic β-lactam antibiotic that is structurally different from other β-lactam antibiotics, such as the penicillins and cephalosporins. Administration of high IV doses of the drug to pregnant rats (15 times the maximum recommended human dose [MRHD]) and rabbits (5 times the MRHD) did not produce embryotoxic, fetotoxic, or teratogenic effects (1–5).
Single 1-g IV doses of aztreonam administered 2–8 hours before elective termination produced detectable concentrations of the antibiotic in fetal serum and amniotic fluid (6). In other studies, the drug was rapidly distributed into cord serum and amniotic fluid (7–11). Six studies have described the pharmacokinetics of aztreonam in pregnancy (7–12). No maternal or fetal adverse effects were reported in these studies.
BREASTFEEDING SUMMARY
Aztreonam is excreted into breast milk (7,11,13). In one study, peak milk concentrations 6 hours after a single 1-g IV dose were <0.4–1.0 mcg/mL (7). In an earlier study, 12 lactating women received a single 1-g dose of the antibiotic either by IM injection (N = 6) or by the IV route (N = 6) (13). Infants were not allowed to breastfeed during the study. Milk and serum samples were collected at scheduled intervals for 8 hours after the dose. In the IM group, the mean peak milk concentration was estimated to be 0.3 mcg/mL, corresponding to a milk:serum ratio of 0.007. Similar calculations for the IV group yielded a peak value of 0.2 mcg/mL and a ratio of 0.002. The low milk concentrations measured in the study were compatible with the acidic nature of the drug and its very low lipid solubility. In another study, the milk concentration was 0.1–0.4 mcg/mL (11).
These data, combined with the poor oral absorption of the antibiotic, indicate that direct systemic effects from the antibiotic in nursing infants are unlikely (13).
The American Academy of Pediatrics classifies aztreonam as compatible with breastfeeding (14).
References
1.Furuhashi T, Kato I, Igarashi Y, Nakayoshi H. Toxicity study of azthreonam: fertility study in rats. Chemotherapy 1985;33:190–202. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:66.
2.Furuhashi T, Ushida K, Sato K, Nakayoshi H. Toxicity study on azthreonam: teratology study in rats. Chemotherapy 1985;33:203–18. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:66.
3.Furuhashi T, Ushida K, Kakei A, Nakayoshi H. Toxicity study on azthreonam: perinatal and postnatal study in rats. Chemotherapy 1985;33:219–31. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:66.
4.Singhvi SM, Ita CE, Shaw JM, Keim GR, Migdalof BH. Distribution of aztreonam into fetuses and milk of rats. Antimicrob Agents Chemother 1984;26:132–5.
5.Product information. Azactam. E. R. Squibb & Sons, 1994.
6.Hayashi R, Devlin RG, Frantz M, Stern M. Concentration of aztreonam in body fluids in mid-pregnancy (abstract). Clin Pharmacol Ther 1984;35:246.
7.Ito K, Hirose R, Tamaya T, Yamada Y, Izumi K. Pharmacokinetic and clinical studies on aztreonam in the perinatal period. Jpn J Antibiot 1990;43:719–26.
8.Matsuda S, Oh K, Hirayama H. Transplacental transfer and clinical application of aztreonam. Jpn J Antibiot 1990;43:700–5.
9.Obata I, Yamato T, Hayashi S, Imakawa N, Hayashi S. Pharmacokinetic study of aztreonam transfer from mother to fetus. Jpn J Antibiot 1990;43:70–80.
10.Cho N, Fukunaga K, Kunii K, Kobayashi I. Studies on aztreonam in the perinatal period. Jpn J Antibiot 1990;43:706–18.
11.Nau H. Clinical pharmacokinetics in pregnancy and perinatology. II. Penicillins. Dev Pharmacol Ther 1987;10:174–98.
12.Cook V, Allen S, Summersgill J, Gall S. The pharmacokinetics of aztreonam during pregnancy (abstract). Am J Obstet Gynecol 1994;170:420.
13.Fleiss PM, Richwald GA, Gordon J, Stern M, Frantz M, Devlin RG. Aztreonam in human serum and breast milk. Br J Clin Pharmacol 1985;19:509–11.
14.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.