Can Bactrim (sulfamethoxazole/trimethoprim) cause Stevens-Johnson syndrome?

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Bactrim and Stevens-Johnson Syndrome

Yes, Bactrim (trimethoprim-sulfamethoxazole) can cause Stevens-Johnson syndrome, which is one of the severe cutaneous adverse reactions associated with this medication. 1

Mechanism and Risk

Trimethoprim-sulfamethoxazole (TMP-SMX) is well-documented as a "high risk" medication for causing severe cutaneous adverse reactions, including:

  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)

The FDA drug label for sulfamethoxazole explicitly lists Stevens-Johnson syndrome among the potentially fatal adverse reactions that can occur with this medication 1. These severe reactions are considered immunologically mediated hypersensitivity reactions.

Clinical Evidence

Multiple guidelines and case reports confirm this association:

  • The American Academy of Dermatology guidelines note that TMP-SMX can cause multiple cutaneous reactions, with Stevens-Johnson syndrome and toxic epidermal necrolysis being the most severe eruptions 2.

  • The FDA drug label warns that "fatalities and serious adverse reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS)" have occurred with TMP-SMX administration 1.

  • Case reports document numerous instances of SJS triggered by TMP-SMX, including cases with initial presentation of mucosal lesions that progressed to full SJS after re-exposure to the drug 3, 4.

Risk Factors

Several factors may increase the risk of developing SJS with TMP-SMX:

  • HIV infection (significantly higher risk) 2
  • Genetic susceptibility factors
  • Concomitant use with other medications that can cause SJS 5
  • History of previous drug reactions

Clinical Presentation and Mortality

SJS presents with:

  • Mucocutaneous tenderness
  • Hemorrhagic erosions
  • Erythema
  • Epidermal detachment (blisters and denuded skin)

The mortality rate for SJS is reported at 1-5%, while TEN (the more severe end of the spectrum) has mortality rates of 25-35% 6. This makes early recognition critical.

Management Recommendations

If SJS is suspected in a patient taking Bactrim:

  1. Immediately discontinue the medication - The FDA label states: "Sulfamethoxazole and trimethoprim should be discontinued at the first appearance of skin rash or any sign of a serious adverse reaction" 1

  2. Provide supportive care, ideally in an intensive care unit

  3. Consider immunomodulating therapies such as high-dose intravenous immunoglobulin

Prevention

For patients with a documented history of SJS related to TMP-SMX, the medication is absolutely contraindicated, as re-exposure can trigger a more severe and potentially fatal reaction 3.

For patients requiring antimicrobial therapy who have a history of SJS with TMP-SMX, alternative antibiotics should be selected based on the specific indication and antimicrobial sensitivity.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Trimethoprim-sulfamethoxazole-induced Stevens-Johnson syndrome: a case report.

Journal of the American Podiatric Medical Association, 2010

Research

Toxic epidermal necrolysis and Stevens-Johnson syndrome.

Orphanet journal of rare diseases, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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