Is azithromycin (a macrolide antibiotic) safe to use during pregnancy, particularly in the first trimester, for a pregnant female with a bacterial infection?

Azithromycin Safety in Pregnancy

Azithromycin is safe to use during pregnancy, including the first trimester, and is the preferred macrolide antibiotic when treatment is indicated. 1, 2

FDA Classification and Animal Studies

• Azithromycin is classified as FDA Pregnancy Category B, with animal reproduction studies in rats and mice at doses 4 and 2 times the human daily dose showing no evidence of fetal harm 3
• The FDA label states there are no adequate and well-controlled studies in pregnant women, but azithromycin should be used during pregnancy when clearly needed 3

Guideline Recommendations

Multiple authoritative guidelines consistently recommend azithromycin as the drug of choice among macrolides during pregnancy:

• The CDC specifically designates azithromycin as the preferred macrolide for pregnant women requiring MAC prophylaxis, explicitly stating it is the "drug of choice" based on animal studies and anecdotal human safety evidence 1, 2
• The 2025 North American guidelines for hidradenitis suppurativa recommend using oral azithromycin in pregnant patients requiring systemic antibiotics, with conditional recommendation strength and moderate quality evidence 1
• The CDC recommends azithromycin 1g orally as a single dose as a treatment option for chlamydial infections during pregnancy 1, 2

Clinical Evidence from Human Studies

• A prospective cohort study of 123 pregnant women exposed to azithromycin (71.6% during first trimester) found no statistically significant increase in major malformations: 3.4% versus 2.3% in disease-matched controls and 3.4% in non-teratogen controls 4
• The rate of major malformations remained within the baseline population risk of 1-3% 4
• Pharmacokinetic studies demonstrate that pregnancy increases the volume of distribution by 86% without significantly changing drug exposure (AUC), suggesting no dose adjustment is needed 5

Critical Distinction from Other Macrolides

Azithromycin is explicitly preferred over clarithromycin and erythromycin during pregnancy:

• Clarithromycin is demonstrated to be teratogenic in animals and should be used with caution or avoided during pregnancy 1, 2
• The 2025 North American guidelines strongly recommend avoiding oral erythromycin due to increased risk of adverse outcomes including elevated liver enzymes 1
• Two studies with >100 women each exposed to clarithromycin in the first trimester showed increased risk of spontaneous abortion 1

Specific Clinical Indications

Azithromycin is recommended for:

• MAC prophylaxis in HIV-infected pregnant women as the drug of choice 1, 2
• Chlamydial infections (1g single dose) 1, 2
• Hidradenitis suppurativa requiring systemic antibiotics 1
• Bacterial respiratory infections when clinically indicated 2
• Pertussis treatment and prophylaxis, particularly for pregnant women by extension from infant data 2

Important Caveats and Limitations

• Some providers may choose to withhold prophylaxis during the first trimester out of general caution about drug exposure, though this is not evidence-based when azithromycin treatment is necessary 1, 2
• A 2022 comprehensive review noted conflicting results across studies regarding risks of spontaneous miscarriage, congenital malformations, preterm birth, and low birth weight, concluding there is no conclusive evidence that azithromycin causes adverse offspring outcomes 6
• Azithromycin has insufficient efficacy data for syphilis treatment in pregnancy and should not be used; penicillin remains the only proven effective treatment 2
• Breast milk transfer studies show median relative cumulative infant dose of 15.7% of maternal dose, exceeding the recommended 10% safety limit, with potential risk of hypertrophic pyloric stenosis (worst-case number needed to harm of 60) 7

Practical Approach

When prescribing azithromycin in pregnancy:

• Use standard dosing without adjustment, as pregnancy does not significantly alter drug exposure despite increased volume of distribution 5
• Prescribe when clinically indicated without unnecessary delay, as the safety profile supports use throughout all trimesters 1, 2, 3
• Monitor for known azithromycin side effects (liver enzyme abnormalities, hearing impairment) as in non-pregnant patients 3
• For chlamydial infections, perform repeat testing 3 weeks after completion of therapy to ensure therapeutic cure 1
• Ensure sexual partners are evaluated and treated; patients should abstain from intercourse for 7 days after single-dose therapy 1