What antibiotics are safe to use during pregnancy?

Safe Antibiotics in Pregnancy

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

First-Line Safe Antibiotics

Beta-Lactams (Preferred)

• Amoxicillin is classified as Category A/B and is compatible throughout all trimesters, with reproduction studies in mice and rats at doses up to 2000 mg/kg showing no evidence of harm to the fetus 2, 1
• Cephalexin has moderate-quality evidence supporting safety throughout pregnancy with no demonstrated fetal harm 3, 1
• 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
• Piperacillin-tazobactam is explicitly listed as "compatible" for use during pre-conception and first trimester 1

Macrolides (Alternative for Penicillin Allergy)

• Azithromycin and erythromycin are considered safe alternatives, particularly for penicillin-allergic patients, though preliminary data on azithromycin remain insufficient for routine recommendation 3
• Erythromycin base 500 mg orally four times daily for 7 days is a recommended regimen for pregnant women with chlamydial infections 3
• Erythromycin estolate is contraindicated during pregnancy due to drug-related hepatotoxicity 3

Other Safe Options

• Clindamycin has moderate evidence supporting safety in pregnancy with no significant risks of congenital anomalies or preterm delivery 3
• Metronidazole is generally considered safe and effective in pregnancy 4
• Nitrofurantoin is considered safe and effective in pregnancy 4
• Fosfomycin is generally considered safe and effective in pregnancy 4

Antibiotics to STRICTLY AVOID

Tetracyclines (Contraindicated)

• Doxycycline and all tetracyclines are contraindicated during pregnancy due to tooth discoloration, transient bone growth suppression, and potential maternal fatty liver of pregnancy 1, 5
• Tetracyclines should not be administered after the fifth week of pregnancy 6, 5

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 3, 1, 5
• Trimethoprim should be avoided during the first trimester due to neural tube defect risk; if necessary, supplement with 5 mg/day folic acid 1, 5
• Sulfonamides should be avoided during the first trimester due to association with hyperbilirubinemia 1

Fluoroquinolones (Contraindicated)

• Quinolones should be strictly avoided due to potential toxicity for the unborn child, including theoretical cartilage damage from animal studies 6, 7
• Ofloxacin is specifically contraindicated for pregnant women 3

Aminoglycosides (Use Only if Life-Threatening)

• Gentamicin and tobramycin are associated with eighth cranial nerve damage and theoretical nephrotoxicity in the fetus 5
• Aminoglycosides should not be prescribed at any time during pregnancy except for life-threatening infections with gram-negative pathogens when other antibiotics have failed 6

Special Considerations by Clinical Scenario

Rifampin-Clindamycin Combination

• This combination may be used in select pregnant patients with severe hidradenitis suppurativa, as rifampin is endorsed by the CDC and WHO as first-line treatment for tuberculosis in pregnancy, supporting its safety 3

Ertapenem

• Data on ertapenem in pregnancy are extremely limited, but animal studies showed no teratogenic evidence, allowing consideration in select recalcitrant cases 3

Vancomycin

• Has limited experience in the first trimester and should only be used for life-threatening infections 5

Critical Pitfalls to Avoid

• Do not discontinue necessary antibiotic therapy due to pregnancy concerns—untreated infections carry significant risks including low birth weight, preterm birth, and spontaneous abortion 4
• Avoid erythromycin estolate specifically—other erythromycin formulations are safe, but the estolate form causes hepatotoxicity 3
• Monitor aminoglycoside serum levels carefully if use is absolutely necessary, as they are safe only with careful monitoring 8
• Remember that physiologic changes in pregnancy (increased glomerular filtration rate, increased total body volume, enhanced cardiac output) may require dose adjustments for renally cleared antibiotics 4