901. Isavuconazole Treatment of Disseminated Zygomycosis
Session: Poster Abstract Session: Antifungal Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
Isavuconazole Treatment of Disseminated Zygomycosis

LS Gagne, SP Hammond, ET Gilmore, AC Joyce, RJ Soiffer, FM Marty

Brigham & Women’s Hosp., Dana-Farber Cancer Inst., Boston, MA.

Background: Zygomycosis (zygo) is a life-threatening infection with limited treatment options. Isavuconazole (ISA) is a promising investigational water soluble triazole drug with anti-zygo activity, favorable pharmacokinetic (PK) profile, and IV and oral availability.

Methods: A 59 y.o. man with relapsed MDS/AML after stem cell transplant receiving reinduction chemotherapy was diagnosed with proven zygo in 9/2009 on skin biopsy, identified as Rhizomucor pusillus/miehei by DNA sequencing. Zygo involved lungs (7 cm consolidation with reverse halo sign, other nodules), brain (multiple abscesses, 2-4 cm), and multiple skin nodules. He received liposomal amphotericin (LAmB) for a month with improvement, then switched to posaconazole for discharge home. He was readmitted with seizure and worsening brain edema 10 days later and switched back to LamB with stabilization. He developed S. aureus catheter-related bacteremia and severe LAmB-related potassium wasting that precluded discharge. FDA emergency use IND was obtained to treat with oral ISA in 11/2009, using 600mg/d x 2 days load followed by 200mg/d. Safety monitoring included laboratory, clinical and radiological assessment. ISA levels were measured periodically. Drug and PK were provided by Basilea Pharmaceutica Intl., Basel, Switzerland.

Results: Patient received 29 weeks of ISA until he expired in 6/2010 from refractory leukemia. His zygo improved steadily with no new lesions, decrease in size of lung (50%) and brain (25%) lesions, and resolution of skin lesions and brain edema, despite ongoing AML relapse requiring further treatment with hydroxyurea, sorafenib and azacitidine. Patient experienced mild nausea initially, but resolved. Transient liver enzyme elevations (<2xULN) were noted initially. QTc remained <450msec. No other clinical or laboratory abnormalities have been noted. Trough level was 1.32 μg/mL 2 weeks after ISA started and were 1.85-3.97 μg/mL during treatment.

Conclusion: ISA zygo salvage treatment has been safe and effective in this patient and deserves further systematic study.

Subject Category: M. Mycology including clinical and basic studies of fungal infections

Lisa Gagne, BA, Brigham and Women's Hospital, Boston, MA


L. Gagne, None

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