Background: Cryptococcosis is associated with significant morbidity and mortality. Isavuconazole (ISA) is a novel, broad-spectrum, triazole antifungal agent (IV and PO) developed for treatment of invasive fungal diseases (IFD). It displays potent activity in vitro against Cryptococcus spp. We report outcomes in a subset of patients enrolled in the VITAL trial with cryptococcosis.
Methods: VITAL was a Phase 3, open-label, multi-center trial conducted to evaluate efficacy and safety of ISA in patients with emerging IFD. Patients received ISA 200 mg TID for 2 days followed by 200 mg QD (IV or PO). Proven/probable IFD (EORTC/MSG criteria) and overall response at end-of-treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed.
Results: Nine patients were treated with ISA for cryptococcosis. The pathogens isolated were Cryptococcus neoformans (n=4) and C. gattii (n=3); 1 patient had histological evidence only, and 1 had positive antigen testing only. Three patients had isolated pulmonary disease and 2 had central nervous system (CNS) disease. The remaining patients had disseminated disease in the lung, CNS, and/or blood or other organ. CLSI MICs were available for 7 patients and ranged from 0.008–0.12 mg/L. Mean duration of therapy was 132 days (range 6–182 days). Six patients had primary therapy with ISA; 2 were intolerant to amphotericin B (AmB; alone or with fluconazole), and 1 was refractory to AmB + fluconazole. Eight patients were alive through ≥84 days: 6 were treatment successes (2 complete, 4 partial) and 2 were treatment failures (both stable) at EOT. All patients with C. gattii infection were treatment successes. One of the stable patients was switched to amphotericin B + 5-flucytosine at Day 25. One of the 9 patients died on Day 7 and was considered a treatment failure (progression) at EOT. Adverse events (AEs) and drug-related AEs were experienced by 8 and 3 patients, respectively.
Conclusion: Cryptococcosis, caused by either C. neoformans or C. gattii, was successfully managed in this small group of patients, supporting further research into this disease.
ClinicalTrials.gov Identifier: NCT00634049
- ICAAC 54th (2014)