Severe agranulocytosis during prolonged trimethoprim-sulfamethoxazole therapy in an elderly male: a case report with causality assessment and literature review

Abstract

Idiosyncratic drug-induced agranulocytosis (IDIA) is a rare but potentially life-threatening adverse drug reaction, most frequently associated with antithyroid drugs, clozapine, and certain antimicrobials. Trimethoprim–sulfamethoxazole (TMP–SMX), commonly prescribed for urinary tract infections (UTIs), carries a documented risk of agranulocytosis, particularly in elderly patients. We describe an 84-year-old male admitted for post-critical illness rehabilitation who developed severe febrile agranulocytosis during prolonged TMP–SMX therapy for UTI. Due to a documentation error following physician rotation, TMP–SMX (80/400 mg, two tablets every 12 hours) was administered for 31 days. On hospital day 24, he developed fever (39.4 °C), diffuse erythematous rash, leukocytes 1.2×10⁹/l, absolute neutrophils 0.01×10⁹/l, lymphocytes 0.52×10⁹/l, and CRP 112 mg/l. TMP–SMX was discontinued and replaced by ciprofloxacin, later cefuroxime, while the patient was transferred to an infectious diseases unit where filgrastim (G-CSF) was initiated, resulting in normalization of leukocytes (7.6×10⁹/l) and neutrophils (4.46×10⁹/l) within seven days. Causality assessment using the Naranjo algorithm yielded a score of 7, consistent with a probable association. This case underscores the importance of accurate antibiotic stop-dates, baseline and periodic complete blood count monitoring during prolonged TMP-SMX therapy, and prompt recognition and management of febrile agranulocytosis in elderly patients.