Prospective study: no rise in fetal anomalies with azithromycin use; May be good first-line choice in pregnancy

OB/GYN News, May 15, 2004 by Diana Mahoney

MIAMI BEACH -- Gestational exposure to azithromycin was not associated with an increased risk above baseline for major fetal anomalies in a prospective, controlled trial of 369 pregnant women.

The antibiotic had a safety profile comparable to the profiles of other nonteratogenic agents. The results of the trial suggest that the drug may be a good first-line choice for some infections that occur in pregnancy, particularly among traditionally noncompliant populations, because of its demonstrated efficacy and simple one-dose regimen, Moumita Sarkar reported in a poster presentation given at the annual meeting of the American Society for Clinical Pharmacology and Therapeutics.

To date, available human studies addressing gestational use of azithromycin have focused primarily on efficacy, not fetal safety.

"It's clear the drug is effective, but is it safe to use during pregnancy? These findings give professionals caring for pregnant women an evidence-based option for treating infections," said Ms. Sarkar of the Hospital for Sick Children in Toronto.

She and her associates at the hospital evaluated the pregnancy outcomes of 123 women who were treated with azithromycin for a range of indications including skin, upper and lower respiratory tract, and genitourinary infections. Eighty-eight of the women were treated during the first trimester.

The outcomes were compared with those of 123 women receiving nonteratogenic antibiotics for similar indications and 123 women receiving other nonteratogenic agents. The three groups were matched for gestational age at the time the drug was prescribed, maternal age, and smoking and alcohol status.

Differences in the rates of major malformations among the three groups were not significant. The rate for the azithromycin-exposed group was 3.4%, compared with 2.3% and 3.4% for the other-antibiotic and other-agent groups, respectively.

In addition to its simple dosing regimen, azithromycin has several therapeutic advantages over first-line antibiotics such as erythromycin and amoxicillin. These include better tissue penetration, broader antimicrobial spectrum, and fewer gastrointestinal side effects. The results may be particularly important for the treatment of chlamydial infections in pregnant women, given the poor efficacy of amoxicillin and erythromycin for this indication and the limited compliance with erythromycin because of frequent side effects, she said.

With regard to the treatment of chlamydia in pregnancy, the Centers for Disease Control and Prevention lists azithromycin as an alternative regimen to the recommended regimens of 7 days of either erythromycin or amoxicillin, citing insufficient safety and efficacy data but acknowledging that early clinical experience and preliminary data suggest the drug is safe and effective.

Azithromycin may be more cost effective than other antibiotics in treating pregnant populations with historically poor compliance (such as adolescents), because it provides an opportunity for single-dose, directly observed therapy, Ms. Sakar said.

Rates of Major Fetal Malformations By In Utero Drug Exposure

Azithromycin                        3.4%
Nonteratogenic Antibiotics          2.3%
Other Nonteratogenic Agents         3.4%

Note: Table made from bar graph.

BY DIANA MAHONEY

New England Bureau