Drug Interaction Leads to Subtherapeutic Treatment for Patient with Fungal Brain Abscess

Six days after increasing the dose, voriconazole concentration was still low in the patient
Six days after increasing the dose, voriconazole concentration was still low in the patient

When treating patients with the antifungal agent voriconazole, it is important to perform close therapeutic drug monitoring when concurrent use of dexamethasone is necessary. The outcome of this interaction is detailed in a recent case study published in the Journal of Clinical Pharmacy and Therapeutics.

The patient, an 84-year-old man, was transferred to the hospital after a 2-day history of progressive right-sided weakness. His past medical history included type 2 diabetes, hyperlipidemia, and gastroesophageal reflux disease. Examination of the patient indicated right facial droop, right upper extremity plegia, expressive aphasia. A brain CT revealed a 1.9 x 1.6cm lesion in the left frontal parietal region with vasogenic edema and mass effect, but no midline shift.

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To control the cerebral edema, the patient was started on dexamethasone 4mg every 8 hours and three days after admission, he underwent stereotactic brain biopsy of the lesion. In response to aspiration of purulent material, cefepime, vancomycin and metronidazole were initiated; histopathology later showed neutrophilic infilitrates and hyphae which prompted the initiation of voriconazole 6mg/kg (400mg) every 12 hours for two doses followed by 4mg/kg (250mg) every 12 hours for 1 week, then 200mg every 12 hours thereafter. On day 4 of treatment, voriconazole was converted from IV to oral formulation.

Cultures from the aspirate showed Cladophialophora bantiana and the final diagnosis of fungal abscess suggestive of cerebral phaeohyphomycosis was made. After 5 days of voriconazole therapy and after showing clinical improvement, the patient was discharged to a skilled nursing facility; voriconazole treatment along with dexamethasone 4mg every 8 hours was continued. However, on day 20 of voriconazole/dexamethasone treatment, the patient was readmitted due to a decline in cognitive function and reduced oral intake. A brain MRI was ordered and the test revealed the lesion size to be 2.9 x 2.4cm; subtherapeutic voriconazole concentration was determined to be the probable cause of disease progression and the dose was increased to 250mg every 12 hours.

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