Treatment and mortality outcomes in patients with other extrapulmonary cryptococcal disease compared with central nervous system disease

Abstract

BackgroundDetermining the extent of cryptococcal disease (CD) is key to therapeutic management. Treatment with fluconazole is only recommended for localised pulmonary disease. Induction therapy with amphotericin B (AmB) and flucytosine is recommended for disease at other sites, irrespective of central nervous system (CNS) involvement, but this is not often followed in patients without meningitis. In this study, we compared treatment and mortality between patients with CD of the CNS and other extrapulmonary (OE) sites.MethodsThis is a retrospective, single‐centre study of all hospitalised patients with nonpulmonary cryptococcal infection from 2002 to 2015 who underwent lumbar puncture. Demographics, predisposing factors, comorbidities, clinical presentation, laboratory values, antifungal treatment and mortality data were collected to evaluate 90‐day mortality and treatment differences between patients with OE and CNS CD. Survival analysis was performed using multivariable Cox regression analysis.ResultsOf 193 patients analysed, 143 (74%) had CNS CD and 50 (26%) had OE CD. Ninety‐day mortality was 23% and similar between the OE and CNS CD groups (22% vs 23%, p = .9). In the comorbidity‐adjusted multivariable Cox regression model, mortality risk was similar in the OE and CNS groups. Fewer patients with OE CD received induction therapy with AmB and flucytosine compared to those with CNS disease (28% vs 71.3%, p < .001).ConclusionPatients with OE CD had similar 90‐day mortality compared to those with CNS disease. Despite current guideline recommendations, patients with OE disease were less likely to receive appropriate induction therapy with AmB and flucytosine compared to patients with CNS disease.

Clinical and microbiologic outcomes of central nervous system cryptococcosis: Re‐examining the need for a 2‐week cerebrospinal fluid analysis

“…Factors associated with mortality were fungaemia, extra‐CNS involvement, requirement of ICU level of care and initial low CSF lymphocyte percentage—all measures that reflect the extent of involvement, clinical severity or degree of immunocompromise at presentation. One recent report found non‐CNS extrapulmonary involvement to have a similarly high 90‐day mortality rate as CNS cryptococcosis 21 . This is consistent with our cohort, where most patients had multifocal disseminated disease and nearly half were fungaemic on presentation.…”

“…One recent report found non-CNS extrapulmonary involvement to have a similarly high 90-day mortality rate as CNS cryptococcosis. 21 This is consistent with our cohort, where most patients had multifocal disseminated disease and nearly half were fungaemic on presentation. The initial serum and CSF CrAg were also numerically higher among patients who died, suggesting a higher burden of infection, although these markers did not reach statistical significance.…”

“…One in three patients with CNS cryptococcosis in our cohort died within 12 months after diagnosis-a rate that is consistent with prior reports in immunocompromised populations. 1,3,4,20,21 Factors associated with mortality were fungaemia, extra-CNS involvement, requirement of ICU level of care and initial low CSF lymphocyte percentage-all measures that reflect the extent of involvement, clinical severity or degree of immunocompromise at presentation. One recent report found non-CNS extrapulmonary involvement to have a similarly high 90-day mortality rate as CNS cryptococcosis.…”

Comprehensive Analysis and Risk Identification of Pulmonary Cryptococcosis in Non-HIV Patients

“…Extrapulmonary cryptococcosis, whether found in the CNS or other sites, is well known to be associated with a poor prognosis [ 14 , 15 ]. In our study, extrapulmonary involvement was an independently prognostic factor in predicting recurrence or death due to cryptococcosis (aOR 15.93 (95% CI 3.47–73.05), p < 0.001) and recurrence or death from any cause (aOR 3.63 (95% CI 1.11–11.91), p = 0.033) among the overall population.…”

“…Of our patients, 6.9% had extrapulmonary involvement, which was much lower than that seen in patients with HIV infection [ 25 , 26 ]. However, once the infection spreads away from the lungs, the prognosis becomes much worse [ 14 ]. Our data indicate that extrapulmonary involvement is an independently poor prognostic factor.…”