An internal medicine team is evaluating a 67-year-old female who was directly admitted to the hospital with a 24-hour history of high fever, profound weakness, and new-onset gingival bleeding. Her past medical history is notable for seropositive rheumatoid arthritis, essential hypertension, and type 2 diabetes mellitus. Her home medications include weekly oral methotrexate, daily folic acid, lisinopril, and metformin. Review of her recent outpatient records reveals a visit to an urgent care clinic three days prior for dysuria, during which she was prescribed a 7-day course of trimethoprim-sulfamethoxazole.
Upon evaluation, her temperature is 38.2 °C (100.8 °F), blood pressure is 110/70 mmHg, and heart rate is 105/min. Physical examination demonstrates pale conjunctivae and scattered non-blanching petechiae across her lower extremities.
Initial laboratory studies show:
| Test | Result |
|---|---|
| Hemoglobin | 8.4 g/dL |
| Mean corpuscular volume | 108 fL |
| Leukocyte count | 1,500/mm³ |
| Absolute neutrophil count | 400/mm³ |
| Platelet count | 32,000/mm³ |
| Creatinine | 1.6 mg/dL (baseline 0.9 mg/dL) |
Blood and urine cultures have been obtained. Which of the following pharmacologic interventions are immediately indicated for this patient? (Select all that apply)
- Discontinue trimethoprim-sulfamethoxazoleAnswer
- Administer intravenous leucovorinAnswer
- Initiate intravenous cefepimeAnswer
- DAdminister high-dose folic acid
- EInitiate oral ciprofloxacin
Answer
Trimethoprim-sulfamethoxazole must be discontinued as it is the precipitating agent. It interacts with methotrexate by competing for renal tubular secretion and synergistically inhibiting folate synthesis, leading to profound bone marrow suppression.
Intravenous leucovorin (folinic acid) must be administered as it provides a source of active reduced folate that bypasses the inhibited dihydrofolate reductase enzyme, effectively rescuing the bone marrow.
Intravenous cefepime must be initiated because the patient has high-risk febrile neutropenia. With an ANC of 400/mm³ and fever in the setting of acute kidney injury, she requires immediate empiric broad-spectrum intravenous antibiotics with antipseudomonal activity.