Differentiating probable nitrofurantoin-induced drug fever from antipsychotic-induced hyperthermia in a patient receiving clozapine

Nitrofurantoin (NIT) is a commonly utilized antibiotic for the treatment of UTIs. Although well tolerated, NIT is not without potential adverse reactions. This case report details the observation of probable NIT-induced drug fever in a patient receiving clozapine. A 61-year-old female with treatment-refractory schizoaffective disorder was admitted to a psychiatric unit with paranoia and auditory hallucinations, prompting clozapine initiation during day 1 of hospitalization. Due to worsening hallucinations and anxiety, antibiotic therapy with NIT for a presumed UTI was initiated 8 days after admission. Febrile episodes were observed beginning on hospital day (HD) 9, leading to concern for possible neuroleptic malignant syndrome (NMS), which led to clozapine discontinuation. The patient received a total of 3 doses of NIT with continued fever until discontinuation on HD 10. No further complications were encountered, and clozapine was safely resumed on HD 13. Although sparsely described in the medical literature, occurrences of drug fever attributable to NIT are previously reported. A review of the medical literature identified only 5 previously published articles specific to NIT-induced drug fever, none of which specified interruptions of psychotropic therapy for a patient with acute psychiatric decompensation. This case highlights the differential diagnosis of fever related to NIT in a patient receiving clozapine when NMS was initially suspected.