What antibiotics are safe to use during pregnancy?

Safe Antibiotics in Pregnancy

Penicillins (particularly amoxicillin) and 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 and during breastfeeding. 1, 2, 3

First-Line Safe Antibiotics

Beta-Lactams (Preferred)

• Amoxicillin is classified as Category A/B and represents the gold standard for antibiotic use in pregnancy, with extensive human data showing no harm to the fetus at therapeutic doses and compatibility throughout all trimesters and breastfeeding 1, 2, 3, 4
• Cephalexin (first-generation cephalosporin) has moderate-quality evidence supporting safety throughout pregnancy with no demonstrated fetal harm 1, 2, 3
• Ampicillin is an acceptable alternative to penicillin, particularly for Group B Streptococcus prophylaxis, with proven efficacy and safety when administered intravenously 1, 3
• Cefazolin is the preferred agent for penicillin-allergic women without history of anaphylaxis 1, 3
• Amoxicillin-clavulanate is compatible during pregnancy but should be avoided in women at risk of preterm delivery due to a very low risk of necrotizing enterocolitis in the fetus 1, 3

Alternative Safe Options

• Erythromycin base is safe for penicillin-allergic patients (500 mg orally four times daily for 7 days for chlamydial infections), though erythromycin estolate is contraindicated due to drug-related hepatotoxicity 2, 3
• Azithromycin is considered a safe alternative for penicillin-allergic patients, though preliminary data remain insufficient for routine recommendation 3
• Clindamycin has moderate evidence supporting its safety in pregnancy with no significant risks of congenital anomalies or preterm delivery 3
• Metronidazole is considered safe during breastfeeding; if single 2 g dose used, stop feeding for 12-24 hours 2

Antibiotics to STRICTLY AVOID

Tetracyclines (Contraindicated)

• Doxycycline and all tetracyclines should be avoided after the fifth week of pregnancy due to tooth discoloration, transient bone growth suppression, and potential maternal fatty liver of pregnancy 1, 2, 3, 5, 6
• The CDC notes that although tetracyclines are not recommended during pregnancy, their use may be indicated for life-threatening illness (such as anthrax exposure) and doxycycline might be used for a short time (7-14 days) before six months of gestation, as adverse effects on developing teeth and bones are dose-related 7

Sulfonamides and Trimethoprim

• Trimethoprim-sulfamethoxazole (co-trimoxazole) should be avoided, especially during the first trimester, due to increased risk of preterm birth, low birthweight, kernicterus, hyperbilirubinemia, fetal hemolytic anemia, and neural tube defects 1, 2, 3
• If co-trimoxazole is absolutely necessary during the first trimester, supplement with 5 mg/day folic acid 3

Fluoroquinolones

• Ciprofloxacin and all fluoroquinolones should be avoided due to potential fetal cartilage damage in animal studies 1
• Ofloxacin is specifically contraindicated for pregnant women 3

Aminoglycosides

• Gentamicin and tobramycin should be avoided if possible due to eighth cranial nerve toxicity and nephrotoxicity risk, though they may be reserved for life-threatening maternal infections refractory to other antibiotics with careful serum level monitoring 1, 8, 5, 6

Infection-Specific Recommendations

Group B Streptococcus Prophylaxis

• Penicillin G: 5 million units IV initially, then 2.5-3.0 million units IV every 4 hours until delivery (first-line) 1, 2, 3
• Ampicillin: Acceptable alternative with proven efficacy 1, 3
• Cefazolin: For penicillin-allergic patients without high risk of anaphylaxis 1, 3

Chlamydia

• Erythromycin base 500 mg orally four times daily for 7 days OR amoxicillin 500 mg orally three times daily for 7-10 days 2, 3

Anthrax Exposure (Life-Threatening)

• Ciprofloxacin 500 mg twice daily for 60 days OR doxycycline 100 mg twice daily for 60 days may be used in pregnant women for bioterrorism-related anthrax exposure, as the life-threatening nature of the illness justifies the exposure 7

Critical Clinical Pitfalls

Screening Requirements

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

Penicillin Allergy Considerations

• Patients with a history of anaphylaxis, angioedema, respiratory distress, or urticaria to penicillin should not receive penicillin, ampicillin, or cefazolin 1
• Approximately 10% of pregnant women have maternal penicillin allergy, making first-generation cephalosporins a suitable alternative 6

Breastfeeding Monitoring

• Monitor all breastfed infants for gastrointestinal effects when the mother receives antibiotics 1, 2
• Antibiotics in breast milk may cause falsely negative cultures if a febrile infant requires evaluation 1, 2, 3
• Macrolides have very low risk of hypertrophic pyloric stenosis if used during first 13 days (safe after 2 weeks) 2

Dosing Considerations

• Physiologic changes in pregnancy (increased glomerular filtration rate, increased total body volume, enhanced cardiac output) may lead to pharmacokinetic alterations requiring dose adjustment or careful monitoring 9
• Amoxicillin dosing should be modified in pediatric patients 12 weeks or younger due to incompletely developed renal function 4