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

Abstract

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.

Nitrofurantoin: properties and potential in treatment of urinary tract infection: a narrative review

“…This issue has been reported in long-term prophylaxis cases for UTI and elderly patients with renal failure. Generally, NF is considered as a safe antimicrobial drug, but, in 1 per 100,000 patients ( Vickery et al., 2022 ) in long-term use, there may be some risks. The non-drug resistance side effects of NF like hepatotoxicity, neuropathy and pulmonary damages are directly related to the long-term use of this drug ( Wang et al., 2008 ).…”

“…FUO is characterized as temperatures higher than 38.3°C which will elapse more than two weeks after they appear ( Haidar and Singh, 2022 ). According to estimations, 4-7% of empirical antibiotic therapy performed in hospitalized patients induce FUO ( Patel and Gallagher, 2010 ; Vickery et al., 2022 ). NF in oral non-suspension form may be associated with FUO ( Roth and Basello, 2003 ).…”

“…However, the occurrence of these fevers is directly related to patients with an impaired immune system, especially neutropenic patients ( Patel and Gallagher, 2010 ), so it is important to discuss it. A case report published in 2022 observed clozapine-induced fever (CIF) in a 60-year-old woman who was receiving medication related to schizoaffective disorder ( Vickery et al., 2022 ). Fever was reported in this patient following antibiotic therapy with three doses of NF.…”