SHM Converge Scientific Abstract ePoster Gallery-Methotrexate and Bactrim, a Deadly Combination

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This case describes a 60-year-old woman with rheumatoid arthritis, coronary artery disease, HFpEF, COPD, and diabetes who developed severe pancytopenia, encephalopathy, and sepsis. She was taking methotrexate and abatacept for rheumatoid arthritis and had recently received trimethoprim-sulfamethoxazole (TMP-SMX/Bactrim) for an asymptomatic urinary tract infection.<br /><br />The key issue was a dangerous drug interaction: both methotrexate and TMP-SMX interfere with folate metabolism. Methotrexate inhibits dihydrofolate reductase, while TMP-SMX also acts as an antifolate. Together, they can cause profound folate deficiency, severe bone marrow suppression, pancytopenia, and life-threatening complications.<br /><br />During hospitalization, her condition worsened. She developed respiratory failure requiring intubation, severe mucositis with bloody airway obstruction, septic shock, Candida tropicalis fungemia treated with micafungin, diffuse candidiasis, and persistent encephalopathy. EEG showed burst suppression, and MRI revealed a small acute right frontal infarct. Bone marrow biopsy showed hypocellular marrow consistent with drug- and infection-related suppression. Her myelosuppression was attributed to severe folate deficiency. Despite transfusions and resolution of shock and fungemia, she remained critically ill and ultimately died.<br /><br />The report emphasizes important clinical lessons:<br />- Always review methotrexate use before prescribing TMP-SMX.<br />- Avoid the combination when possible.<br />- Use safer alternatives for infections when appropriate.<br />- Monitor CBC closely if the combination is unavoidable.<br />- Do not treat asymptomatic bacteriuria except in specific IDSA-approved situations, such as pregnancy, prior to invasive urologic procedures, or early after renal transplant.<br /><br />Overall, this case highlights how routine prescribing decisions can lead to catastrophic outcomes and underscores the importance of medication reconciliation and guideline-based antibiotic use.

Asset Subtitle

Nathan G. Haverstick

Meta Tag

Author List Nathan G. Haverstick

Category Clinical Vignettes

Concept Methotrexate

Concept Trimethoprim-sulfamethoxazole

Concept Bone Marrow Suppression

Concept Pancytopenia

Concept Antifolate Effect

Distinguished Non-Finalist

Presenter Organization University of South Florida

Presenting Author Nathan G. Haverstick

Track Adult

Keywords

methotrexate

trimethoprim-sulfamethoxazole

pancytopenia

folate deficiency

rheumatoid arthritis

drug interaction

bone marrow suppression

sepsis

encephalopathy

asymptomatic bacteriuria

Methotrexate

Trimethoprim-sulfamethoxazole

Bone Marrow Suppression

Pancytopenia

Antifolate Effect