Probable Trimethoprim/Sulfamethoxazole-Induced Higher-Level Gait Disorder and Nocturnal Delirium in an Elderly Man

OBJECTIVE: To report a case of probable trimethoprim/sulfamethoxazole (TMP/SMX)-induced higher-level gait disorder (HLGD) and nocturnal delirium in an elderly patient on high-dose oral therapy. CASE SUMMARY: An 82-year-old man with a recent history of depression became comatose following an overdose of escitalopram and oxazepam. He was admitted ventilated for 7 days in the intensive care unit, and treated with piperacillin tazobactam and cefepime for aspiration pneumonia. Following discharge to a medical ward, respiratory symptoms persisted and imaging confirmed pulmonary abscesses. Stenotrophomonas maltophilia was isolated from sputum and, on day 15, TMP/SMX 800 mg/160 mg 1 tablet every 12 hours was initiated. On day 35, the dose was increased to 800 mg/160 mg 2 tablets every 12 hours. By day 37, the patient was unsteady when attempting to stand. From day 40, he was noted to have features of HLGD with gait ignition failure, poor balance, and frequent falls. His other medications at this time were thiamine 100 mg daily, multivitamin 1 tablet daily, omeprazole 20 mg every 12 hours, and modified-release venlafaxine 150 mg daily. Investigation did not reveal any cause for his acute gait disturbance. TMP/SMX was stopped on day 48 and, by day 51, the patient's gait had returned to normal. DISCUSSION: Neuropsychiatric adverse reactions with TMP/SMX have been infrequently reported. The Naranjo probability scale indicated that TMP/SMX was the probable cause of HLGD in this patient. CONCLUSIONS: At time of writing, this was the first reported case of HLGD associated with TMP/SMX. Clinicians should consider this adverse reaction as a potential cause of HLGD, especially in the elderly and those with malnutrition and hepatic or renal dysfunction.