Predictors of Mortality and Differences in Clinical Features among Patients with Cryptococcosis According to Immune Status

Abstract

IntroductionCryptococcosis is an invasive fungal infection causing substantial morbidity and mortality. Prognostic factors are largely derived from trials conducted prior to the modern era of antifungal and potent combination antiretroviral therapies, immunosuppression, and transplantation. Data describing the clinical features and predictors of mortality in a modern cohort are needed.MethodsWe conducted a retrospective cohort study of patients at our institution diagnosed with cryptococcosis from 1996 through 2010. Data included demographics, clinical features, diagnostics, treatment, and outcomes.ResultsWe identified 302 individuals: 108 (36%) human immunodeficiency virus (HIV)-positive, 84 (28%) organ transplant recipients (OTRs), and 110 (36%) non-HIV, non-transplant (NHNT) patients including 39 with no identifiable immunodeficiency. Mean age was 49 years, 203 (67%) were male and 170 (56%) were white. All-cause mortality at 90 days was 21%. In multivariable logistic regression analyses, cryptococcemia (OR 5.09, 95% CI 2.54–10.22) and baseline opening pressure >25 cmH2O (OR 2.93, 95% CI 1.25–6.88) were associated with increased odds of mortality; HIV-positive patients (OR 0.46, 95% CI 0.19–1.16) and OTRs (OR 0.46, 95% CI 0.21–1.05) had lower odds of death compared to NHNT patients.ConclusionsPredictors of mortality from cryptococcosis in the modern period include cryptococcemia, high intracranial pressure, and NHNT status while drug(s) used for induction and historical prognostic factors including organ failure syndromes and hematologic malignancy were not associated with mortality.

Plain and contrast‑enhanced chest computed tomography scan findings of pulmonary cryptococcosis in immunocompetent patients

“…Depending on the host immune status, the infection may remain dormant in the lung or may undergo hematogenous spread to any organ system, including the central nervous system (CNS), bones and skin (7,9). However, pulmonary cryptococcosis does not present specific clinical manifestations and radiological findings.…”

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

“…Both bloodstream infection and the presence of pseudocysts and cryptococcal granulomas have been related to treatment failure and to patient death. 8,25,26 A high number of Cryptococcus spp. cells in the CSF, which represents infection with high fungal load was also associated with a poor prognosis.…”

“…Risk factors for a poor prognosis of cryptococcosis, usually defined as death within up to 90 days, include altered mental state, wasting syndrome, bloodstream infection or of another site outside the central nervous system (CNS), and cerebrospinal fluid (CSF) with elevated opening pressure, low leucocyte count, a large number of yeast cells, and high titers of cryptococcal antigens. 7,8 The risk factors for cryptococcosis refractory to treatment and/or relapsing have been less precisely determined, but include infection at sites outside the CNS, a low number of leucocytes in the CSF, and the use of corticosteroids during and after antifungal therapy. 6 In addition to the clinical conditions of the patients, certain characteristics of Cryptococcus spp.…”

Cryptococcosis in Anti-Interferon-Gamma Autoantibody-Positive Patients: a Different Clinical Manifestation from HIV-Infected Patients

“…The clinical characteristics of cryptococcosis among HIV-infected and non-HIV-infected patients have been compared (7)(8)(9). Central nervous system (CNS) involvement, especially meningitis, occurs more frequently in HIV-positive patients, whereas pulmonary involvement is more frequently observed in HIV-negative patients.…”