What antibiotics should be avoided during pregnancy?

Antibiotics to Avoid During Pregnancy

The antibiotics that must be avoided during pregnancy include tetracyclines (especially doxycycline after the first trimester), aminoglycosides (gentamicin, tobramycin), fluoroquinolones, co-trimoxazole/trimethoprim-sulfamethoxazole (particularly first trimester and near term), metronidazole, dapsone, and erythromycin, with the strength of avoidance varying by trimester and specific fetal risks. 1

Strongly Contraindicated Throughout Pregnancy

Tetracyclines (Doxycycline, Minocycline)

• Doxycycline should be avoided during the second and third trimesters and at delivery due to tooth discoloration, transient suppression of bone growth, and potential congenital anomalies. 1
• Tetracyclines bind to fetal bones and teeth, causing permanent discoloration if used after the fifth week of pregnancy. 2, 3
• May exacerbate maternal fatty liver of pregnancy. 1
• If absolutely necessary in the first trimester only, use should be limited and not considered first-choice therapy. 1

Aminoglycosides (Gentamicin, Tobramycin - Systemic)

• Associated with eighth cranial nerve damage and theoretical nephrotoxicity in the fetus. 4
• Carry a small but significant risk of fetal ototoxicity. 2
• Should not be prescribed at any time during pregnancy except for life-threatening infections with gram-negative pathogens when other antibiotics have failed. 3
• Important caveat: Inhaled tobramycin has minimal systemic absorption and is considered compatible during pregnancy if required for clinical stability. 1

Avoid in Specific Trimesters

Co-trimoxazole (Trimethoprim-Sulfamethoxazole)

• Should be avoided during the first trimester and near term due to increased risk of preterm birth, low birthweight, and kernicterus. 1
• Sulfonamide use is associated with neonatal hyperbilirubinemia and fetal hemolytic anemia when used at delivery. 1
• Trimethoprim interferes with folic acid metabolism, potentially increasing risk of neural tube defects and cardiovascular abnormalities. 5
• May be "possibly safe" in the second trimester only if absolutely necessary with folic acid supplementation (at least 400 μg daily). 1, 5

Metronidazole

• Should be avoided due to increased risk of low birthweight and neuroblastoma. 1
• This represents a conditional recommendation with low-quality evidence, but the potential for serious fetal harm warrants avoidance. 1

Use with Extreme Caution (Generally Avoided)

Fluoroquinolones (Ciprofloxacin, Others)

• Most clinicians avoid during pregnancy and lactation due to animal studies showing fetal cartilage damage. 1
• Human data suggest the actual risk may be low, but these remain second-line agents. 1
• If a fluoroquinolone is absolutely indicated, ciprofloxacin should be the chosen agent. 1
• Classified as "possibly safe" but not recommended as first-line therapy. 1

Dapsone

• Should be avoided due to increased risk of preterm birth, low birthweight, and hemolysis. 1
• This is a conditional recommendation with very low-quality evidence. 1

Erythromycin

• Should be avoided due to increased risk of adverse outcomes including elevated liver enzymes. 1
• Erythromycin estolate specifically is avoided due to potential maternal hepatotoxicity. 1
• This represents a strong recommendation despite low-quality evidence. 1

Clarithromycin

• Produced adverse pregnancy outcomes in experimental animals, though human data suggest low risk. 1
• FDA labeling indicates it is not recommended for use in pregnant women except when no alternative therapy is appropriate. 6
• Classified as "probably safe" but should not be first-line. 1

Safe First-Line Alternatives

Preferred Antibiotics During Pregnancy

• Cephalexin (cephalosporin): Safe with moderate-quality evidence. 1
• Azithromycin (macrolide): Safe with moderate-quality evidence. 1
• Clindamycin: Safe with moderate-quality evidence. 1
• Amoxicillin and amoxicillin-clavulanate: Compatible, though avoid amoxicillin-clavulanate in women at risk of preterm delivery due to very low risk of necrotizing enterocolitis. 1
• Cefuroxime and other cephalosporins: Not teratogenic at usual therapeutic doses. 1

Critical Clinical Pitfalls

Common Mistakes to Avoid

• Do not assume inhaled aminoglycosides carry the same risk as systemic formulations—inhaled tobramycin is actually compatible. 1
• Do not use amoxicillin-clavulanate in women at risk for preterm delivery. 1
• Do not prescribe tetracyclines after the fifth week of pregnancy under any circumstances. 3
• Always supplement with folic acid (≥400 μg daily) if trimethoprim must be used. 5

Timing Considerations

• First trimester exposures carry the highest risk for congenital malformations (organogenesis period). 1
• Third trimester and delivery exposures risk neonatal complications (hyperbilirubinemia, kernicterus, hemolytic anemia). 1
• Second trimester may allow slightly more flexibility for certain agents like co-trimoxazole when safer alternatives have failed. 5