Treatment and outcomes among patients with Cryptococcus gattii infections in the United States Pacific Northwest

Abstract

Background: Cryptococcus gattii is a fungal pathogen causing an emerging outbreak in the United States Pacific Northwest (PNW). Treatment guidelines for cryptococcosis are primarily based on data from C. neoformans infections; applicability to PNW C. gattii infection is unknown. We evaluated the relationship between initial antifungal treatment and outcomes for PNW C. gattii patients.

Methods: Cases were defined as culture-confirmed invasive C. gattii infections among residents of Oregon and Washington States during 2004-2011. Clinical data were abstracted from medical records through one year of follow-up. Recommended initial treatment for central nervous system (CNS), bloodstream, and severe pulmonary infections is amphotericin B and 5-flucytosine; for non-severe pulmonary infections, recommended initial treatment is fluconazole. Alternative initial treatment was defined as any other initial antifungal treatment.

Results: Seventy patients survived to diagnosis; 50 (71%) received the recommended initial treatment and 20 (29%) received an alternative. Fewer patients with pulmonary infections [21 (64%)] than CNS infections [25 (83%)] received the recommended initial treatment (p = 0.07). Among patients with pulmonary infections, those with severe infections received the recommended initial treatment less often than those with non-severe infections (11% vs. 83%, p<0.0001). Eight patients with severe pulmonary infections received alternative initial treatments; three died. Four patients with non-severe pulmonary infections received alternative initial treatments; two died. There was a trend towards increased three-month mortality among patients receiving alternative vs. recommended initial treatment (30% vs. 14%, p = 0.12), driven primarily by increased mortality among patients with pulmonary disease receiving alternative vs. recommended initial treatment (42% vs. 10%, p = 0.07).

Conclusions: C. gattii patients with pulmonary infections--especially severe infections--may be less likely to receive recommended treatment than those with CNS infections; alternative treatment may be associated with increased mortality. Reasons for receipt of alternative treatment among C. gattii patients in this area should be investigated, and clinician awareness of recommended treatment reinforced.