Cryptococcus gattii infection: Treatment
- Sharon Chen, PhD, MBBS, FRACP, FRCPA
Sharon Chen, PhD, MBBS, FRACP, FRCPA
- Clinical Associate Professor
- Sydney Medical School, University of Sydney
- Kieren A Marr, MD
Kieren A Marr, MD
- Section Editor — Compromised Host Infections; Fungal Infections
- Professor of Medicine and Oncology
- Johns Hopkins University School of Medicine
- Tania C Sorrell, MD
Tania C Sorrell, MD
- Professor of Clinical Infectious Diseases and Director of the Centre for Infectious Diseases and Microbiology
- Sydney Medical School, University of Sydney
Cryptococcus gattii has emerged as an important fungal pathogen. Infection manifests most often as potentially fatal meningoencephalitis and/or pulmonary disease. The emergence of clusters of cryptococcosis due to C. gattii in British Columbia, Canada, in 1999, with subsequent spread to the United States Pacific Northwest, has challenged our understanding of this disease [1,2]. C. gattii infection had previously been detected infrequently and was thought to be largely restricted to tropical and subtropical regions, including Australia and Papua New Guinea. It is now clear that sporadic cases occur in various regions around the world.
The antifungal treatment and other aspects of management of C. gattii infection will be reviewed here. The microbiology, epidemiology, pathogenesis, clinical manifestations, and diagnosis of C. gattii infection are discussed separately; Cryptococcus neoformans infection is also reviewed elsewhere. (See "Cryptococcus gattii infection: Microbiology, epidemiology, and pathogenesis" and "Cryptococcus gattii infection: Clinical features and diagnosis" and "Microbiology and epidemiology of Cryptococcus neoformans infection" and "Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-infected patients" and "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-seronegative patients" and "Cryptococcus neoformans infection outside the central nervous system" and "Treatment of Cryptococcus neoformans meningoencephalitis and disseminated infection in HIV seronegative patients".)
At present, there are no guidelines with interpretative clinical minimum inhibitory concentration (MIC) breakpoints to recognize antifungal susceptibility or resistance in C. gattii. Only C. neoformans has been included in the Clinical Laboratory Standard Institutes (CLSI) guidelines for testing of yeasts . Clinical breakpoints and epidemiologic cut-off values based on MIC distributions of wild-type strains of C. gattii are being studied [4-6]. Despite these limitations, MICs, most commonly determined by broth microdilution, have been reported for C. gattii and may provide help to clinicians in the management of C. gattii infection .
Many studies have documented low antifungal MICs against C. gattii and C. neoformans that have not increased over time [8-10]. However, in some regions, concern has arisen over whether C. gattii may be less susceptible than C. neoformans to some antifungal agents. A group in Brazil reported significantly higher geometric mean MICs for fluconazole, voriconazole, amphotericin B, and flucytosine against C. gattii compared with C. neoformans . In a study from Spain, fluconazole, voriconazole, and posaconazole MICs were significantly higher against C. gattii than against C. neoformans , whilst in Taiwan, C. gattii has been reported to be less susceptible to flucytosine and amphotericin B .
In vitro susceptibility to azoles appears to vary among C. gattii genotypes, with several studies showing that C. gattii genotype VGII has higher fluconazole MICs than other genotypes [5,14-18], including one study of 90 clinical and environmental isolates of C. gattii from the Pacific Northwest of North America . Although the clinical implications of higher fluconazole MICs have not been determined, there is major interest in this issue since C. gattii genotype VGII is the genotype associated with the ongoing outbreak of C. gattii infection in the Pacific Northwest of North America (table 1). (See "Microbiology and epidemiology of Cryptococcus neoformans infection".)
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- ANTIFUNGAL SUSCEPTIBILITIES
- Central nervous system disease
- - Meningoencephalitis
- Induction therapy
- Consolidation and maintenance therapy
- - Cerebral cryptococcomas
- Isolated pulmonary disease
- IRIS-like syndrome
- MONITORING DURING THERAPY
- ADVERSE EFFECTS
- Amphotericin B
- SUMMARY AND RECOMMENDATIONS