What antibiotics are safe to use during pregnancy?

Antibiotics Safe in Pregnancy

Penicillins (amoxicillin, amoxicillin-clavulanate, piperacillin-tazobactam) 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, 2

First-Line Safe Antibiotics

Beta-Lactams (Preferred)

• Amoxicillin is classified as Category A/B and is compatible throughout all trimesters and during breastfeeding 1, 2
• Cephalexin has moderate-quality evidence supporting safety throughout pregnancy with no demonstrated fetal harm 1, 3
• Amoxicillin-clavulanate is compatible during pregnancy (Category B1/B), though avoid in women at risk of preterm delivery due to 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, 4
• Ceftazidime and other cephalosporins are safe throughout pregnancy with no evidence of fetal damage in animals or increased risk in human case reports 1

Macrolides (Generally Safe)

• Azithromycin (Category B1/B) is probably safe with moderate-quality evidence supporting use in pregnancy 1
• Erythromycin (Category A/B) is probably safe, though erythromycin estolate should be avoided due to potential maternal hepatotoxicity 1
• Clarithromycin (Category B3/C) is probably safe despite adverse outcomes in animal studies; human data suggest low risk 1
• Caution: Very low risk of hypertrophic pyloric stenosis in infants exposed to macrolides during first 13 days of breastfeeding (not after 2 weeks) 1

Other Safe Options

• Clindamycin has moderate-quality evidence supporting safety in pregnancy 1
• Metronidazole (Category B2/B) is possibly safe if no safer alternatives exist; if using single 2g dose during breastfeeding, stop feeding for 12-24 hours 1
• Rifampin (Category C/C) is possibly safe but requires vitamin K supplementation to mother and neonate to prevent bleeding risk 1

Antibiotics to AVOID

Strongly Contraindicated

• Doxycycline and tetracyclines should be avoided during T2 and T3 due to tooth discoloration, transient bone growth suppression, and potential maternal fatty liver of pregnancy 1
• Co-trimoxazole (trimethoprim-sulfamethoxazole) should be avoided, especially during T1, due to increased risk of preterm birth, low birthweight, kernicterus, hyperbilirubinemia, and fetal hemolytic anemia 1
• Fluoroquinolones (ciprofloxacin) should be avoided despite Category B3/C classification; associated with fetal cartilage damage in animals, though human data suggest low risk 1
• Aminoglycosides (gentamicin, tobramycin) should be avoided if possible due to eighth cranial nerve toxicity and potential nephrotoxicity in the fetus 1

Conditional Avoidance

• Erythromycin should be avoided per 2025 guidelines due to increased risk of adverse outcomes including elevated liver enzymes 1
• Dapsone may increase risk of preterm birth, low birthweight, and hemolysis 1

Special Considerations by Trimester

First Trimester (T1)

• Avoid co-trimoxazole and trimethoprim due to neural tube defect risk; if necessary, supplement with 5 mg/day folic acid 1
• Concern exists that amoxicillin exposure during organogenesis may be associated with oral clefts, though risk is very low 1
• Sulfonamides should be avoided due to association with hyperbilirubinemia 1

Second/Third Trimester (T2/T3)

• Tetracyclines are strictly contraindicated after week 5 of pregnancy 1
• Avoid sulfonamides at delivery due to risk of fetal hemolytic anemia 1

Labor and Delivery

• Rifampin requires vitamin K administration to both mother and neonate to prevent bleeding 1
• Avoid sulfonamides at delivery 1

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
• Tobramycin: avoid breastfeeding for 2 hours following IV injection when concentration is maximal 1

Clinical Pitfalls to Avoid

• Do not withhold necessary antibiotics due to pregnancy concerns when serious maternal infection exists; untreated infections carry significant risks including abortion, preterm labor, and low birth weight 5, 6, 7
• Approximately 1 in 4 pregnant women will be prescribed antibiotics, accounting for 80% of prescription medications in pregnancy 6
• Physiologic changes in pregnancy (increased GFR, total body volume, cardiac output) may require dose adjustments for renally cleared antibiotics 6
• Nitrofurantoin and sulfonamides are frequently prescribed despite ACOG 2011 recommendations to avoid in first trimester due to birth defect risks 5