Approaches to Antifungal Therapies and Their Effectiveness among Patients with Cryptococcosis

Abstract

The goal of this study was to determine the degree to which the persistence of cryptococcosis, overall 1-year mortality, and 1-year mortality due to cryptococcosis were influenced by initial antifungal treatment regimen in a cohort of adults with cryptococcosis treated at a tertiary care medical center. Risk factors, underlying conditions, treatment, and mortality information were obtained for 204 adults with cryptococcosis from Duke University Medical Center (DUMC) from 1996 to 2009. Adjusted risk ratios (RR) for persistence and hazard ratios (HR) for mortality were estimated for each exposure. The all-cause mortality rate among patients with nonsevere disease (20%) was similar to that in the group with disease (26%). However, the rate of cryptococcosisattributable mortality with nonsevere disease (5%) was much lower than with severe disease (20%). Flucytosine exposure was associated with a lower overall mortality rate (HR, 0.4; 95% confidence interval [CI], 0.2 to 0.9) and attributable mortality rate (HR, 0.5; 95% CI, 0.2 to 1.2). Receiving a nonrecommended antifungal regimen was associated with a higher relative risk of persistent infection at 4 weeks (RR, 1.9; 95% CI, 0.9 to 4.3), and the rate of attributable mortality among those not receiving the recommended dose of initial therapy was higher than that of those receiving recommended dosing (HR, 2.3; 95% CI, 1.0 to 5.0). Thus, the 2010 Infectious Diseases Society of America (IDSA) guidelines are supported by this retrospective review as a bestpractice protocol for cryptococcal management. Future investigations should consider highlighting the distinction between allcause mortality and attributable mortality so as not to overestimate the true effect of cryptococcosis on patient death.

Cryptococcosis

“…133,134 This combination represents the most potent fungicidal regimen, with faster CSF sterilization and fewer relapses, and is associated with lower attributable mortality. 133–139 Because the interruption of induction therapy is associated with poorer outcome, in resource-available areas the liposomal product has become the preferred polyene. Unfortunately, there are still no comparative studies with 5-FC combined with lipid formulations of amphotericin B as opposed to AmBd.…”

Refractory and/or Relapsing Cryptococcosis Associated with Acquired Immune Deficiency Syndrome: Clinical Features, Genotype, and Virulence Factors of Cryptococcus spp. Isolates

“…The combination of flucytosine with amphotericin B improves the prognosis of patients with cryptococcosis and failure to use flucytosine may contribute to the persistence of infection and to the higher lethality observed. 29 The causes of the persistence and relapse of cryptococcosis were investigated among the underlying diseases and also in the respective fungal isolates. Factors leading to an unfavorable outcome were observed in both patient groups such as alcoholism, late beginning of antifungal treatment, problems in using amphotericin B because of its toxicity, poor adherence to treatment, and the previous or concomitant use of corticosteroids.…”

Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches

“…The outcomes are even worse for aspergillosis despite the use of voriconazole (Herbrecht et al 2002). In resource-rich regions with access to amphotericin B and 5-flucytosine, the 1-year mortality owing to cryptococcosis is approximately 25% (Bratton et al 2013), whereas in resource-limited regions where fluconazole is the only available therapy the mortality is much higher (Sloan et al 2009). As pointed out in an excellent essay on the state of the art for the diagnosis and treatment of fungal disease, the poor outcomes for invasive fungal infections are most likely owing to relatively poor diagnostic methods as well as the need for more effective therapy (Brown et al 2012).…”