What antibiotics are safe to use during pregnancy?

Safe Antibiotics in Pregnancy

Penicillins (amoxicillin, ampicillin) and first-generation cephalosporins (cephalexin) are the safest first-line antibiotics during pregnancy, with extensive human data showing no teratogenic effects at therapeutic doses across all trimesters. 1

First-Line Safe Antibiotics (All Trimesters)

Beta-Lactams - Preferred Agents

• Amoxicillin is classified as Category A/B and compatible throughout all trimesters and during breastfeeding, with decades of clinical experience documenting safety 1, 2
• Cephalexin has moderate-quality evidence supporting safety throughout pregnancy with no demonstrated fetal harm 1
• Ampicillin is recommended for intrapartum prophylaxis, particularly for Group B Streptococcus, with demonstrated efficacy and safety when administered intravenously 1
• Cefazolin is suitable for intrapartum prophylaxis with a relatively narrow spectrum and high intra-amniotic concentrations 1
• Penicillin G is recommended for Group B Streptococcus prophylaxis at 5 million units IV initially, then 2.5-3 million units IV every 4 hours until delivery 1

Special Considerations for Beta-Lactams

• 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
• Piperacillin-tazobactam is explicitly listed as compatible for use during pre-conception and first trimester 1

Alternative Agents for Penicillin Allergy

• Azithromycin and erythromycin are considered safe alternatives for penicillin-allergic patients, though preliminary data on azithromycin remain insufficient for routine recommendation 1
• Erythromycin base 500 mg orally four times daily for 7 days is recommended for pregnant women with chlamydial infections 1
• Erythromycin estolate is contraindicated during pregnancy due to drug-related hepatotoxicity 1
• Clindamycin has moderate evidence supporting its safety in pregnancy with no significant risks of congenital anomalies or preterm delivery 1

Additional Safe Options

• Metronidazole is considered safe during pregnancy and breastfeeding 4
• Nitrofurantoin is generally considered safe and effective in pregnancy 5
• Fosfomycin is generally considered safe and effective in pregnancy 5
• Vancomycin has limited first-trimester experience and should only be used for life-threatening infections 3, 4

Antibiotics to STRICTLY AVOID

Tetracyclines - Contraindicated

• Doxycycline and all tetracyclines are strictly contraindicated after week 5 of pregnancy due to tooth discoloration, transient bone growth suppression, and potential maternal fatty liver of pregnancy 1, 3, 4

Sulfonamides and Trimethoprim - High Risk

• Co-trimoxazole (TMP-SMX) should be avoided, especially during the first trimester, due to increased risk of preterm birth, low birthweight, kernicterus, hyperbilirubinemia, and fetal hemolytic anemia 1, 3
• Trimethoprim should be avoided during the first trimester due to neural tube defect risk; if absolutely necessary, supplement with 5 mg/day folic acid 1, 3
• Sulfonamides should be avoided during the first trimester due to association with hyperbilirubinemia 1, 3

Fluoroquinolones - Contraindicated

• Ofloxacin is specifically contraindicated for pregnant women 1
• All fluoroquinolones should be avoided due to theoretical cartilage damage concerns 4

Aminoglycosides - Reserved for Life-Threatening Infections Only

• Gentamicin and tobramycin are associated with eighth cranial nerve damage and nephrotoxicity, and should be reserved only for life-threatening infections with careful monitoring 3, 4

Antifungals - High-Dose Contraindicated

• High-dose fluconazole (≥400 mg/day) during the first trimester is associated with craniosynostosis and dysmorphic facies; doses over 150 mg/day are linked to miscarriage 3, 4

Trimester-Specific Considerations

First Trimester - Critical Period

• Avoid co-trimoxazole and trimethoprim due to neural tube defect risk 1, 3
• Avoid sulfonamides due to hyperbilirubinemia association 1, 3
• Tetracyclines are strictly contraindicated after week 5 1, 3
• Penicillins and first-generation cephalosporins remain first-line with extensive safety data 1, 3

Second and Third Trimesters

• Amoxicillin-clavulanate should be avoided in women at risk of preterm delivery 1, 3
• Continue penicillins and cephalosporins as first-line agents 1

Breastfeeding Considerations

Safe During Breastfeeding

• Penicillins (amoxicillin, ampicillin) are compatible with breastfeeding and considered low risk 4
• Cephalosporins (cefuroxime, ceftriaxone, cefadroxil) are compatible with low oral bioavailability in infants 4
• Amoxicillin/clavulanic acid is safe and effective with FDA Category B rating 4
• Metronidazole is considered safe during breastfeeding 4

Use with Caution During Breastfeeding

• Fluoroquinolones should not be used as first-line; if necessary, ciprofloxacin is preferred 4
• Aminoglycosides should be avoided for 2 hours following IV injection; monitor renal function and auditory testing if prolonged 4
• Oral clindamycin may increase risk of gastrointestinal side effects in the infant 4
• Doxycycline should be limited to maximum 3 weeks without repeating courses 4
• Macrolides (azithromycin, erythromycin) have very low risk of hypertrophic pyloric stenosis if used during first 13 days; safe after 2 weeks 4

Critical Monitoring

• All breastfed infants should be monitored for gastrointestinal effects such as diarrhea and altered flora when mother receives antibiotics 4
• Antibiotics in breast milk may cause falsely negative cultures if a febrile infant requires evaluation 1, 4
• Co-trimoxazole is compatible with breastfeeding in healthy term babies but should be avoided in babies who are G6PD deficient, jaundiced, or premature 1

Common Pitfalls to Avoid

• Do not withhold necessary antibiotics due to pregnancy concerns when serious maternal infection is present; untreated infections carry significant risks including preterm birth and spontaneous abortion 5
• Do not use erythromycin estolate - use erythromycin base instead 1
• Do not prescribe tetracyclines or fluoroquinolones as routine agents during pregnancy 1, 3, 4
• Monitor for altered pharmacokinetics - pregnancy increases glomerular filtration rate, total body volume, and cardiac output, which may require dose adjustments 5
• Avoid aminoglycosides unless life-threatening gram-negative infection with treatment failure of recommended antibiotics 3