A 59 yo male, with a background of recently treated aplastic anaemia on posaconazole prophylaxis, presented with mucormycosis with pulmonary and contiguous splenic involvement. He was commenced on liposomal amphotericin and underwent a left lower lobectomy and muscle flap transposition. Culture and pan-fungal PCR were negative. Due to radiological progression (evidence of a new splenic lesion on serial imaging) posaconazole was added and titrated up to a dose of 300mg QID following sub-therapeutic trough levels. The patient remained clinically stable, however developed drug related toxicity with renal impairment and nausea unresponsive to multiple anti-emetics. Treatment was changed to isavuconazole monotherapy. The patient responded well, with radiological resolution of the splenic lesions and improvement in both nausea and renal function. Discussion: Mucormycosis carries a high mortality rate with few therapeutic options available. Early treatment with liposomal amphotericin and surgical resection is the current recommended management. Our patient demonstrated progressive disease on amphotericin monotherapy and ongoing treatment was limited by nephrotoxicity. The use of posaconazole in mucormycosis has been limited by poor bioavailability and unpredictable pharmacokinetics, as evidenced in our patient, who never achieved therapeutic levels and was unable to tolerate high dose posaconazole due to nausea. To the best of our knowledge, this is the first case of mucormycosis treated with isavuconazole in Australia. Isavuconazole is a broad spectrum triazole with in vitro activity against Mucorales, as well as clinical efficacy demonstrated in a phase 3 trial (VITAL) and case reports. It has a favourable pharmacokinetic profile with excellent bioavailability, a large volume of distribution and long half-life that allows once daily dosing. We achieved therapeutic levels in our patient with minimal adverse effects. Isavuconazole has potential as both primary and salvage therapy in mucormycosis, especially in patients unable to tolerate amphotericin based therapy.
Full conference title:
- ISHAM 19th (2015)