What antibiotics are safe to use during pregnancy?

Antibiotics Safe in Pregnancy

First-Line Safe Antibiotics: Use These First

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, 3

• Amoxicillin is classified as FDA Category A/B with extensive human data showing no teratogenic effects at therapeutic doses up to 3-6 times the human dose in animal studies, and is explicitly compatible throughout all trimesters including the critical first trimester. 1, 2, 3, 4

• Cephalexin (first-generation cephalosporin) has moderate-quality evidence supporting safety throughout pregnancy with no demonstrated fetal harm and should be prioritized for patients with non-anaphylactic penicillin allergies. 1, 2, 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

• Piperacillin-tazobactam is explicitly listed as "compatible" for use during pre-conception and first trimester, with all penicillins considered low risk based on decades of clinical experience. 1, 3

• Ampicillin is recommended for intrapartum Group B Streptococcus prophylaxis and has proven efficacy and safety when administered intravenously. 2

Safe Alternative Antibiotics for Specific Situations

• Azithromycin is considered safe during pregnancy for chlamydial infections with no adverse effects reported in studies, though preliminary data remain insufficient for routine recommendation in all scenarios. 2, 5

• Erythromycin base (NOT erythromycin estolate) is a safe alternative for penicillin-allergic patients, with a recommended regimen of 500 mg orally four times daily for 7 days for chlamydial infections. 1, 2, 3

• Clindamycin has moderate evidence supporting its safety in pregnancy with no significant risks of congenital anomalies or preterm delivery. 1

• Cefazolin is suitable for intrapartum prophylaxis with a relatively narrow spectrum of activity and high intra-amniotic concentrations, particularly for penicillin-allergic patients without high risk of anaphylaxis. 2

• Metronidazole, nitrofurantoin, and fosfomycin are generally considered safe and effective in pregnancy, though nitrofurantoin and sulfonamides should be avoided in the first trimester when other options are available. 5

Antibiotics to STRICTLY AVOID in Pregnancy

These antibiotics carry definite risks to the fetus and should only be used for life-threatening maternal indications:

• Tetracyclines (including doxycycline) are strictly contraindicated after week 5 of pregnancy due to tooth discoloration (brown, yellow, or gray staining), transient bone growth suppression, and potential maternal fatty liver of pregnancy. 6, 1, 2, 3

• Trimethoprim-sulfamethoxazole (co-trimoxazole) should be avoided, especially during the first trimester, due to neural tube defect risk, increased risk of preterm birth, low birthweight, kernicterus, hyperbilirubinemia, and fetal hemolytic anemia. 1, 2, 3

• Fluoroquinolones (such as ciprofloxacin and levofloxacin) should be avoided due to potential fetal cartilage damage demonstrated in animal studies and potential fetal toxicity affecting cartilage development. 2, 3

• Erythromycin estolate is specifically contraindicated during pregnancy due to drug-related hepatotoxicity, though erythromycin base remains safe. 1, 3

• Aminoglycosides (such as gentamicin and tobramycin) carry definite risk to the fetus in all trimesters with known ototoxicity and nephrotoxicity, and should only be used for vital indications with careful serum level monitoring. 6

• Quinolones are FDA group D drugs with definite risk to the fetus in all trimesters and should only be used for vital indications. 6

Trimester-Specific Considerations

First Trimester (Most Critical Period):

• Avoid co-trimoxazole and trimethoprim due to neural tube defect risk; if necessary, supplement with 5 mg/day folic acid. 1, 3
• Avoid sulfonamides due to association with hyperbilirubinemia. 1
• Tetracyclines are strictly contraindicated after week 5. 1, 3

Second and Third Trimesters:

• Sulfonamides should be avoided near term due to risk of kernicterus and hyperbilirubinemia in the newborn. 1, 3
• Women treated for syphilis during the second half of pregnancy are at risk for premature labor and/or fetal distress if treatment precipitates the Jarisch-Herxheimer reaction. 6

Special Clinical Scenarios

For Syphilis:

• Penicillin is the ONLY proven effective treatment for preventing maternal transmission and treating fetal infection; pregnant women with penicillin allergy should be desensitized and treated with penicillin. 6, 2
• There are no proven alternatives to penicillin for syphilis treatment during pregnancy. 6

For Group B Streptococcus Prophylaxis:

• Penicillin G: 5 million units IV initially, then 2.5-3 million units IV every 4 hours until delivery. 2
• Ampicillin is an acceptable alternative with proven efficacy. 2
• Cefazolin for penicillin-allergic patients without high risk of anaphylaxis. 2

For Infective Endocarditis:

• Penicillin, ampicillin, amoxicillin, erythromycin, mezlocillin, and cephalosporins can be given during all trimesters (FDA group B). 6
• Vancomycin, imipenem, rifampicin, and teicoplanin are FDA group C (risk cannot be excluded; risk-benefit must be carefully considered). 6

Critical Clinical Pitfalls to Avoid

• Never delay necessary antibiotic treatment due to pregnancy concerns when maternal infection poses serious risk; untreated infections can lead to preterm labor, low birth weight, and sepsis. 7, 5

• Screen all pregnant women for asymptomatic bacteriuria and Group B Streptococcus at 35-37 weeks gestation. 2, 3

• Do NOT use nitrofurantoin or sulfonamides in the first trimester unless other antimicrobial therapies are deemed clinically inappropriate, despite their historical use for UTIs. 7

• Antibiotic prophylaxis is NOT recommended during vaginal or caesarean delivery for endocarditis prevention, given lack of convincing evidence that infective endocarditis is related to delivery. 6

Breastfeeding Considerations

• Most systemic antibiotics are present in breast milk and could cause falsely negative cultures in febrile infants or gastroenteritis due to altered intestinal flora. 1

• Co-trimoxazole is compatible with breastfeeding in healthy term babies but should be avoided in babies who are G6PD deficient, jaundiced, or premature. 1

• After intravenous tobramycin, avoid breastfeeding for 2 hours following injection when drug concentration is maximal. 3

• Penicillins may lead to sensitization of infants; caution should be exercised when amoxicillin is administered to a nursing woman. 4