Is Bactrim (trimethoprim/sulfamethoxazole) safe to use during pregnancy?

Bactrim in Pregnancy: Safety Considerations

Bactrim (trimethoprim/sulfamethoxazole) should be avoided during pregnancy due to increased risks of preterm birth, low birthweight, neural tube defects, cardiovascular malformations, and kernicterus in the newborn. 1, 2

Risks Associated with Bactrim Use During Pregnancy

First Trimester Concerns

• Increased risk of congenital malformations, particularly:
  • Cardiovascular abnormalities (35% higher risk compared to β-lactams) 3
  • Neural tube defects (due to folate antagonism) 4
  • Oral clefts (3.2 times higher risk of cleft lip and palate) 3
  • Urinary tract defects 5

Third Trimester Concerns

• Risk of kernicterus (hyperbilirubinemia) in the newborn due to displacement of bilirubin from albumin binding sites 4
• Increased risk of preterm birth 2
• Low birthweight 2

Evidence Quality and Recommendations

The 2025 North American clinical practice guidelines for hidradenitis suppurativa specifically recommend avoiding oral co-trimoxazole (trimethoprim/sulfamethoxazole) during pregnancy due to the increased risks mentioned above (Conditional recommendation, Low quality evidence) 2.

The FDA drug label for sulfamethoxazole states that while there are no large, well-controlled studies, some retrospective epidemiologic studies suggest an association between first trimester exposure and increased risk of congenital malformations 4. The drug label also warns that sulfamethoxazole may interfere with folic acid metabolism and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Safer Antibiotic Alternatives During Pregnancy

For pregnant patients requiring antibiotics, the following safer alternatives are recommended:

1. First-line options:

   • Cephalexin (Conditional recommendation, Moderate evidence) 2
   • Azithromycin (Conditional recommendation, Moderate evidence) 2
   • Amoxicillin/penicillins (FDA Pregnancy Category B) 1

2. Second-line option:

   • Clindamycin (Conditional recommendation, Moderate evidence) 2

Special Considerations

If Bactrim must be used during pregnancy in exceptional circumstances (such as for life-threatening infections with no alternatives):

• Folic acid supplementation (at least 400 μg daily) is strongly recommended to reduce the risk of neural tube defects 1
• Avoid use in the third trimester due to the risk of kernicterus 1
• Use the lowest effective dose for the shortest duration possible

Recent Research Evidence

A 2025 population-based cohort study of 71,604 pregnancies found that TMP-SMX exposure during the first trimester was associated with a 35% higher risk of any congenital malformation, a 2.09-fold increased risk of severe cardiac malformations, and a 3.23-fold increased risk of cleft lip and palate compared to β-lactam antibiotics 3.

Clinical Decision Algorithm

1. Is the patient pregnant?

   • Yes → Avoid Bactrim; consider safer alternatives
   • No → Bactrim may be appropriate based on infection type

2. If pregnant, is there an absolute necessity for Bactrim? (e.g., severe infection with documented resistance to all safer alternatives)

   • Yes → Consider risks vs. benefits, add folic acid supplementation, use shortest course possible
   • No → Use safer alternatives (cephalexin, azithromycin, amoxicillin)

3. Which trimester?

   • First trimester → Highest risk of congenital malformations
   • Third trimester → High risk of kernicterus; absolutely contraindicated

The evidence clearly demonstrates that the risks of Bactrim during pregnancy outweigh the benefits in most clinical scenarios, and safer alternatives should be used whenever possible.