title: 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 cryptococcosis-attributable 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 best-practice protocol for cryptococcal management. Future investigations should consider highlighting the distinction between all-cause mortality and attributable mortality so as not to overestimate the true effect of cryptococcosis on patient death.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. emily_bratton@unc.edu
authors.forename: Emily W
authors.initials: EW
authors.lastname: Bratton
authors.forename: Nada
authors.initials: N
authors.lastname: El Husseini
authors.forename: Cody A
authors.initials: CA
authors.lastname: Chastain
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lee
authors.forename: Charles
authors.initials: C
authors.lastname: Poole
authors.forename: Til
authors.initials: T
authors.lastname: Stürmer
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Juliano
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003453:Cryptococcosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D004334:Drug Administration Schedule; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use; D005437:Flucytosine / Q000008:administration & dosage / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine