Clinical Management and Outcomes of Patients in the Duke Cryptococcosis Clinical Cohort, 1996–2009

Bratton, Emily Wenink

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March 22, 2019

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Bratton, Emily Wenink
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology

Abstract

Using this single-center cohort of cryptococcosis patients, we characterized temporal trends among HIV-infected, transplant recipients and a third heterogeneous group of HIV-negative, non-transplant patients, over a 14-year period (1996 - 2009). We executed a comparison of clinical management and predictors of poor outcomes with respect to these three groups. Adherence to recommended treatment algorithms was an important research question in our study. The 2010 IDSA Guidelines for treatment of these three groups was created to better inform clinicians, yet supportive evidence from cohort studies is still lacking, particularly in the HIV-negative, non-transplant group. All cryptococcosis patients diagnosed at Duke University Medical Center from 1996 - 2009 were included in our study (N=207). Although the total cases have remained steady (~15/year), there was a shift to a decreasing proportion of HIV-positive patients with a concomitant increase in HIV-negative cases, while transplant recipients remained steady. From the start of antifungal therapy overall mortality through one year was 25% (n=52). Cryptococcosis-attributable mortality through one year of follow-up was 15% (n=31); half of these deaths were among HIV-negative, non-transplant cases. Acute mortality was high, with 10% of severe disease patient deaths occurring during the first two weeks from the start of antifungal treatment. As recommended, most patients with severe disease received amphotericin B for initial antifungal treatment and the majority of non-severe patients received fluconazole. Receiving a non-recommended antifungal regimen was associated with a higher relative risk of persistent infection at four weeks (RR1.9, 95%CI 0.9 - 4.3). The rate of attributable mortality among those not receiving the recommended dose of initial therapy was higher relative to those receiving recommended dosing (HR 2.3, 95%CI 1.0 - 5.0). Among severe disease patients, flucytosine exposure was associated with a lower overall mortality rate (HR 0.4, 95%CI 0.2 - 0.9) and attributable mortality (HR 0.5, 95%CI 0.2 - 1.2). The future of cryptococcosis treatment and the development of new antifungal therapies should not only be informed by randomized trials, but also by key observational trends that help to identify problematic, real-world applications of drug regimens to diverse populations.

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