What antibiotics are safe to use during pregnancy?

Safe Antibiotics During Pregnancy

Penicillins (particularly amoxicillin) and first-generation cephalosporins (particularly cephalexin) are the safest first-line antibiotics during pregnancy, with decades of clinical experience demonstrating no teratogenic effects and compatibility throughout all trimesters. 1, 2

First-Line Safe Antibiotics

Amoxicillin is the preferred first-line agent for most bacterial infections in pregnancy, classified as FDA Category A/B with extensive human data showing no harm to the fetus at therapeutic doses and compatibility throughout all trimesters and during breastfeeding. 1, 2, 3 Reproduction studies in mice and rats at doses up to 2000 mg/kg (3-6 times the human dose) showed no evidence of fetal harm. 3

Cephalexin is the preferred first-generation cephalosporin, with moderate-quality evidence supporting safety throughout pregnancy and no demonstrated fetal harm. 4, 1, 2 This should be prioritized for patients with non-anaphylactic penicillin allergies. 2

Additional safe penicillins and cephalosporins include:

• Ampicillin - particularly effective for Group B Streptococcus prophylaxis when administered intravenously 1
• Penicillin G - recommended at 5 million units IV initially, then 2.5-3.0 million units IV every 4 hours until delivery for Group B Streptococcus prophylaxis 1, 5
• Cefazolin - preferred for penicillin-allergic women without history of anaphylaxis, with high intra-amniotic concentrations 1, 2
• Cefuroxime and ceftazidime - safe throughout pregnancy with no demonstrated fetal harm 1
• Ceftriaxone - safe throughout pregnancy 1

Safe Alternative Antibiotics for Penicillin-Allergic Patients

Azithromycin is considered a safe alternative for penicillin-allergic patients, with moderate-quality evidence supporting its safety in pregnancy. 4, 1, 2

Erythromycin base (NOT erythromycin estolate) is safe for penicillin-allergic patients at 500 mg orally four times daily for 7 days. 1, 2 Erythromycin estolate is specifically contraindicated due to hepatotoxicity. 2 However, one recent guideline recommends avoiding oral erythromycin due to increased risk of adverse outcomes including elevated liver enzymes. 4

Clindamycin has moderate evidence supporting its safety in pregnancy with no significant risks of congenital anomalies or preterm delivery. 4, 1, 2 For hidradenitis suppurativa specifically, oral clindamycin monotherapy may be considered, though data are less robust; rifampin and clindamycin combination can be used in select patients with severe disease. 4

Metronidazole is considered safe during pregnancy and breastfeeding, though if a single 2g dose is used during breastfeeding, feeding should be stopped for 12-24 hours. 1, 5 However, for hidradenitis suppurativa, oral metronidazole should be avoided due to potential increased risk of low birthweight and neuroblastoma. 4

Antibiotics to STRICTLY AVOID

Doxycycline and all tetracyclines must be avoided after the fifth week of pregnancy due to tooth discoloration, transient bone growth suppression, and potential maternal fatty liver of pregnancy. 4, 1, 2, 5, 6 This is a strong recommendation with low-quality evidence. 4

Trimethoprim-sulfamethoxazole (TMP-SMX/co-trimoxazole) should be avoided, especially during the first trimester, due to increased risk of preterm birth, low birthweight, kernicterus, hyperbilirubinemia, and fetal hemolytic anemia. 4, 1, 2, 5 If necessary during the first trimester, supplement with 5 mg/day folic acid due to neural tube defect risk. 2

Fluoroquinolones (such as ciprofloxacin) should be avoided due to potential fetal cartilage damage demonstrated in animal studies. 1, 2

Dapsone should be avoided due to potential increased risk of preterm birth, low birthweight, and hemolysis. 4

Aminoglycosides (gentamicin, tobramycin) should be avoided if possible due to eighth cranial nerve toxicity and nephrotoxicity risk, with definite risk to the fetus in all trimesters. 1, 2 They should only be used for life-threatening infections with careful serum level monitoring. 6, 7

Infection-Specific Recommendations

Group B Streptococcus Prophylaxis

• First-line: Penicillin G - 5 million units IV initially, then 2.5-3.0 million units IV every 4 hours until delivery 1, 5
• Alternative: Ampicillin - proven efficacy for intrapartum prophylaxis 1
• For penicillin allergy without high-risk features: Cefazolin 1, 2

Chlamydia Treatment

• Erythromycin base 500 mg orally four times daily for 7 days OR amoxicillin 500 mg orally three times daily for 7-10 days 1, 5

Syphilis Treatment

Penicillin is the ONLY proven effective treatment for preventing maternal transmission and treating fetal infection. 1, 2 Pregnant women with penicillin allergy should be referred for skin testing and desensitization, as no alternatives have been proven effective and safe for prevention of fetal infection. 1, 2

Critical Clinical Pitfalls to Avoid

All pregnant women must be screened for asymptomatic bacteriuria and Group B Streptococcus at 35-37 weeks gestation. 1, 2, 5

Patients with history of anaphylaxis, angioedema, respiratory distress, or urticaria to penicillin should NOT receive penicillin, ampicillin, or cefazolin. 1

Physiologic changes in pregnancy lead to increased glomerular filtration rate, increased total body volume, and enhanced cardiac output, which may require dose adjustments or careful monitoring for renally cleared antibiotics. 8

Breastfeeding Considerations

Penicillins and cephalosporins are compatible with breastfeeding and considered low risk. 5 Most systemic antibiotics are present in breast milk and could cause falsely negative cultures in febrile infants or gastroenteritis due to altered intestinal flora. 2

Metronidazole is safe during breastfeeding, though if a single 2g dose is used, stop feeding for 12-24 hours. 1, 5

Macrolides have very low risk of hypertrophic pyloric stenosis if used during first 13 days (safe after 2 weeks). 5

Monitor all breastfed infants for gastrointestinal effects when mother receives antibiotics. 5