Is Azithromycin (a macrolide antibiotic) safe to use in a pregnant female patient during the second trimester of pregnancy for treatment of a bacterial infection?

Azithromycin Use in Second Trimester of Pregnancy

Azithromycin is safe to use during the second trimester of pregnancy and is the preferred macrolide antibiotic for treating bacterial infections in pregnant women. 1, 2

Safety Profile and Recommendation Basis

• The CDC specifically designates azithromycin as the drug of choice during pregnancy based on animal studies showing no teratogenic effects and no conclusive evidence of adverse fetal outcomes in humans. 3, 1

• The FDA classifies azithromycin as Pregnancy Category B, with animal reproduction studies at doses up to 4 times (rats) and 2 times (mice) the human daily dose of 500 mg showing no evidence of harm to the fetus. 4

• A prospective cohort study of 123 pregnant women (71.6% exposed during first trimester) found no statistically significant increase in major malformations compared to disease-matched controls (3.4% vs 2.3%) or non-teratogen controls (3.4%), with rates remaining within the baseline 1-3% expected in the general population. 5

Clinical Indications During Second Trimester

Azithromycin is recommended for the following bacterial infections:

• Chlamydial infections: 1g orally as a single dose 2
• Atypical pneumonia (Mycoplasma, Chlamydia, Legionella): 500mg on day 1, then 250mg daily for days 2-5 2, 6
• Community-acquired pneumonia: Combination therapy with a beta-lactam (ampicillin-sulbactam, ceftriaxone, or cefotaxime) plus azithromycin 500mg daily for hospitalized patients 6
• Pertussis treatment or prophylaxis: Azithromycin is the preferred macrolide 1, 2

Critical Safety Distinction: Avoid Clarithromycin

• Never substitute clarithromycin for azithromycin during pregnancy. Clarithromycin has demonstrated teratogenic effects in animal studies and is classified as DIII (should not be used) by the CDC. 3, 2, 6

• This distinction is crucial because both are macrolides, but they have fundamentally different safety profiles in pregnancy. 2, 6

Monitoring and Precautions

• Monitor for QT prolongation risk, hepatotoxicity, and Clostridium difficile-associated diarrhea, as these are standard azithromycin precautions applicable to all patients. 2, 6

• After 20 weeks gestation, monitor for preterm labor when treating pneumonia, as pneumonia itself increases the risk of preterm delivery independent of antibiotic use. 2, 6

• Prothrombin times should be carefully monitored if azithromycin is co-administered with oral anticoagulants, as post-marketing reports suggest potential potentiation of anticoagulant effects. 4

Common Pitfalls to Avoid

• Do not withhold azithromycin during the second trimester out of excessive caution. The CDC specifically recommends its use throughout pregnancy when clinically indicated, and some providers who withhold during first trimester do so without evidence-based justification. 3, 6

• Do not use doxycycline as an alternative, as it causes fetal tooth discoloration and bone effects. 2

• Do not use fluoroquinolones unless maternal necessity justifies fetal exposure for life-threatening infections when other options have failed. 2

Alternative Considerations

• Erythromycin is an acceptable macrolide alternative if azithromycin cannot be used, though it causes more gastrointestinal side effects. 2

• Amoxicillin is the safest first-line choice for typical bacterial lower respiratory tract infections throughout pregnancy when atypical coverage is not required. 2