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 for pregnant women, with decades of clinical experience demonstrating no teratogenic effects and compatibility throughout all trimesters. 1, 2

First-Line Safe Antibiotics

Penicillins

• Amoxicillin is the gold standard, 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
• All penicillins are considered low risk based on decades of clinical experience 2, 4
• Piperacillin-tazobactam is explicitly compatible for use during pre-conception and first trimester 2
• Important caveat: Amoxicillin-clavulanate should be avoided in women at risk of preterm delivery due to a very low risk of necrotizing enterocolitis in the fetus 2

Cephalosporins

• Cephalexin (first-generation) has moderate-quality evidence supporting safety throughout pregnancy with no demonstrated fetal harm 1, 2
• First-generation cephalosporins should be prioritized over newer generations 5
• All cephalosporins are considered first-line agents with established safety profiles 6, 7

Alternative Safe Options for Penicillin-Allergic Patients

• Erythromycin base is safe throughout pregnancy (avoid erythromycin estolate due to hepatotoxicity) 2, 4
• Azithromycin is considered safe, though preliminary data remain insufficient for routine first-line recommendation 2
• Clindamycin has moderate evidence supporting safety with no significant risks of congenital anomalies or preterm delivery 2

Other Compatible Antibiotics

• Metronidazole is considered safe during pregnancy 6, 7
• Nitrofurantoin is generally considered safe and effective 6
• Fosfomycin is generally considered safe 6

Antibiotics to STRICTLY AVOID

Tetracyclines (Including Doxycycline)

• Contraindicated after week 5 of pregnancy due to tooth discoloration, transient bone growth suppression, and potential maternal fatty liver of pregnancy 1, 2, 7

Trimethoprim-Sulfamethoxazole (Co-trimoxazole)

• Avoid especially during first trimester due to increased risk of preterm birth, low birthweight, kernicterus, hyperbilirubinemia, fetal hemolytic anemia, and neural tube defects 1, 2
• If absolutely necessary, supplement with 5 mg/day folic acid 2

Fluoroquinolones

• Contraindicated throughout pregnancy including ofloxacin 2, 6, 5

Aminoglycosides

• Should not be prescribed at any time during pregnancy due to nephrotoxicity and ototoxicity 7
• Reserved only for life-threatening infections with gram-negative pathogens when other antibiotics have failed, with careful serum level monitoring 4, 5

Infection-Specific Recommendations

Group B Streptococcal Infection

• Penicillin G: 5 million units IV initially, then 2.5 million units IV every 4 hours until delivery 1
• Screen all pregnant women at 35-37 weeks gestation 1

Chlamydia

• Erythromycin base 500 mg orally four times daily for 7 days, OR
• Amoxicillin 500 mg orally three times daily for 7-10 days 1, 2

Asymptomatic Bacteriuria

• Screen all pregnant women 1
• Treat with first-line agents (amoxicillin or cephalexin)

Critical Clinical Pitfalls to Avoid

• Never assume maternal penicillin allergy is absolute—approximately 10% of pregnant women report penicillin allergy, making cephalosporins a suitable alternative 5
• Avoid amoxicillin-clavulanate in women at risk of preterm delivery despite amoxicillin alone being safe 2
• Do not use sulfonamides during first trimester due to neural tube defect risk 2
• Erythromycin estolate is specifically contraindicated (use erythromycin base instead) 2
• Physiologic changes in pregnancy (increased glomerular filtration rate, increased total body volume, enhanced cardiac output) may require dose adjustments for renally cleared antibiotics 6

Breastfeeding Considerations

• Penicillins and cephalosporins are compatible with breastfeeding and considered low risk 1, 8
• Metronidazole is safe; if single 2g dose used, stop feeding for 12-24 hours 1, 8
• Monitor all breastfed infants for gastrointestinal effects when mother receives antibiotics 1, 8
• Macrolides carry very low risk of hypertrophic pyloric stenosis if used during first 13 days (safe after 2 weeks) 1, 8
• Antibiotics in breast milk may cause falsely negative cultures if febrile infant requires evaluation 1, 8