(631) Challenging Voriconazole Dosing and Monitoring in a Patient With an Acute Burn Injury

Introduction: Voriconazole (VCZ) is an antifungal agent approved as a first-line therapy for the treatment of invasive Aspergillosis. It demonstrates nonlinear pharmacokinetics (PK), displays variable plasma concentrations, and has a narrow therapeutic index, therefore drug level monitoring is recommended. Patients who present with burn injuries are at a high risk of invasive fungal infections and may require VCZ therapy. In this setting, VCZ PK can be further impacted by the significant physiological changes associated with burn injuries. For this reason, achieving and maintaining therapeutic VCZ levels can be challenging, thus the optimal strategy for dosing and monitoring in this setting remains unclear.

Description: A 30 year-old male presented with a 70% total body surface area burn. Despite appropriate care, the patient developed an invasive Aspergillus wound infection. Given concerns of systemic infection, the patient was initiated on intravenous VCZ with a loading dose of 6mg/kg for two doses and was transitioned to 200mg twice daily (BID) via nasogastric tube. A VCZ trough level was collected on day five of oral therapy and resulted subtherapeutic at 0.5mcg/mL with a trough goal of 1 to 4mcg/mL. The VCZ dose was increased to 300mg BID, with a resulting therapeutic trough level of 3.2mcg/mL. However, a repeat trough level collected two weeks later returned subtherapeutic at 0.5mcg/mL. Over several weeks, the VCZ dose was adjusted further with both subtherapeutic and supratherapeutic levels noted despite doses being given as scheduled and tube feeds held appropriately around the doses. Oral intake and other medication therapies were consistent throughout his treatment course; however, the patient did require multiple surgical debridements and grafting of the burn and experienced fluctuations in his renal function. The VCZ dose was ultimately modified to 700mg BID after eight weeks of adjustments before consistent therapeutic levels were achieved.

Discussion: Therapeutic VCZ levels were difficult to achieve in the setting of acute burns likely due to physiological changes associated with the injury. Patients with burn injuries who require VCZ may need higher initial starting doses, closer drug monitoring and/or dual therapy to ensure adequate treatment of invasive fungal infections.