Can Bactrim (sulfamethoxazole/trimethoprim) be given to pregnant women?

Bactrim Use in Pregnancy

Bactrim (sulfamethoxazole/trimethoprim) should generally be avoided during pregnancy, particularly in the first trimester and near term, due to risks of congenital malformations and neonatal complications, though it may be used in the second trimester when safer alternatives are unavailable and the maternal infection poses greater risk than the medication. 1, 2

Risk Profile by Trimester

First Trimester - Avoid

• Epidemiologic studies suggest an association between first-trimester exposure and increased risk of congenital malformations, including neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot. 2
• The FDA drug label explicitly warns about embryofetal toxicity and states that if used during pregnancy, patients should be advised of potential hazards to the fetus. 2
• The 2025 hidradenitis suppurativa guidelines specifically recommend avoiding oral co-trimoxazole in pregnant patients due to increased risk of preterm birth, low birthweight, and kernicterus. 1

Second Trimester - Use with Caution

• Cotrimoxazole can be used with more confidence during the second and third trimesters when the risk of neural tube defects is lower. 3
• The European Respiratory Society guidelines classify co-trimoxazole as "avoid" during pregnancy but note it is "possibly safe" during breastfeeding. 1
• For specific high-risk infections like Q fever during pregnancy, long-term cotrimoxazole therapy is recommended to decrease the risk of placentitis and obstetric complications, as the risk of acquiring serious infections outweighs the antimicrobial drug-related adverse effects. 3

Third Trimester and Near Term - Avoid

• Sulfonamide use is associated with hyperbilirubinemia of the neonate and fetal hemolytic anemia when used at delivery. 1
• The 2005 CDC pertussis guidelines state that TMP-SMZ should not be administered to pregnant women because of the potential risk for kernicterus among infants. 1
• Clinicians should be aware of the risk for neonatal hyperbilirubinemia when cotrimoxazole is prescribed in the third trimester. 3

Risk Mitigation Strategies

Folic Acid Supplementation

• All women capable of becoming pregnant should consume at least 400 μg of folic acid daily from supplements, fortified foods, or both, to reduce the risk of neural tube defects, especially if taking cotrimoxazole. 3
• Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, supplementation is particularly important. 2, 4

Alternative Antibiotics

• For urinary tract infections in pregnant women, consider cephalexin, azithromycin, or amoxicillin as safer first-line alternatives. 5
• For patients with penicillin allergy, macrolides (except erythromycin estolate) may be considered as alternatives. 3
• The 2025 hidradenitis suppurativa guidelines suggest using oral cephalexin, azithromycin, or clindamycin as safer systemic antibiotic options during pregnancy. 1

Clinical Decision Algorithm

When Bactrim might be considered:

1. Maternal infection is serious and poses significant risk (e.g., Q fever, severe UTI with resistant organisms)
2. Patient is in second trimester (weeks 14-27)
3. Safer alternatives have failed or are contraindicated
4. Patient is receiving adequate folic acid supplementation (≥400 μg daily)

Absolute contraindications:

• First trimester exposure (weeks 0-13) unless life-threatening maternal infection
• Near term or at delivery (risk of neonatal kernicterus and hemolytic anemia)
• Infants younger than 2 months of age (contraindicated for breastfeeding mothers with young infants)

Common Pitfalls

• Do not prescribe Bactrim for routine UTIs in pregnant women when safer alternatives like cephalexin are available. 5
• Despite a 2011 ACOG committee opinion recommending against sulfonamides in the first trimester, data from 2014 showed nitrofurantoin and trimethoprim-sulfamethoxazole were still among the most frequently prescribed antibiotics during the first trimester. 5
• The safety of trimethoprim in pregnant women has not been established, and indiscriminate use could foster resistance. 6
• Animal studies showed teratologic effects (mainly cleft palates) at doses of 533 mg/kg sulfamethoxazole or 200 mg/kg trimethoprim in rats. 4

Breastfeeding Considerations

• Levels of sulfamethoxazole and trimethoprim in breast milk are approximately 2% to 5% of the recommended daily dose for infants over 2 months of age. 2
• Caution should be exercised when administering to nursing women, especially when breastfeeding jaundiced, ill, stressed, or premature infants because of the potential risk of bilirubin displacement and kernicterus. 2
• Compatible with breastfeeding in healthy term babies; avoid in babies who are glucose-6-phosphate dehydrogenase deficient, jaundiced, or premature. 1