Cryptococcal Meningitis: A Retrospective Cohort of a Brazilian Reference Hospital in the Post-HAART Era of Universal Access

Hindawi Canadian Journal of Infectious Diseases and Medical Microbiology Volume 2018, Article ID 6512468, 5 pages https://doi.org/10.1155/2018/6512468 Research Article Cryptococcal Meningitis: A Retrospective Cohort of a Brazilian Reference Hospital in the Post-HAART Era of Universal Access Aline Z. de Azambuja, Gustavo Wissmann Neto, Guilherme Watte, Luciana Antoniolli, and Luciano Z. Goldani Section of Infectious Diseases, Hospital de Clı́nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil Correspondence should be addressed to Luciano Z. Goldani; Received 9 May 2018; Revised 1 July 2018; Accepted 12 July 2018; Published 1 August 2018 Academic Editor: Aim Hoepelman Copyright © 2018 Aline Z. de Azambuja et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome worldwide. However, limited data exist for HIV-infected patients in the post-HAART (highly active antiretroviral therapy) era in Brazil. The aim of this study was to describe the clinical characteristics and outcomes of cryptococcosis in a cohort of patients attending a teaching tertiary care hospital in southern Brazil after the introduction of HAART in Brazil. Patients and Methods. A retrospective study was conducted in tertiary care hospital in southern Brazil. Detailed data on risk factors, clinical manifestations, diagnosis methods, treatment, and prognosis of patients with meningeal cryptococcosis were evaluated from January 2009 to December 2016. Results. Seventy-nine cases of cryptococcal meningitis were identified. Most of the patients presented positive CSF (cerebrospinal fluid) cultures for Cryptococcus neoformans (96%). The prevalence of males and females with meningeal cryptococcosis was similar. The age of the patients ranged from 5 to 67 years. The median time of hospitalization was 28 days. The most common underlying disease was HIV (82%), followed by solid transplant (10%). Fever, nausea, vomiting, headache, and altered mental status were the most common clinical manifestations. Initial opening intracranial pressures varied from 30 to 130 cm H2O. CNS imaging abnormalities include hydrocephalus and hypodensities. Widened Virchow–Robin spaces were described in only 2 patients (2.5%). Induction treatment of the majority of the patients consisted of amphotericin B and flucytosine (67%) followed by amphotericin B and fluconazole (19%). Multivariate analysis of Cox regression identified headache at presentation, mechanical ventilation, CSF glucose <20 mg/dL, and CSF cryptococcal antigen ≥1 : 1000 for independent risk factors for death. All-cause 30-day and 60-day mortalities were 19% and 24%, respectively. Conclusions. Meningeal cryptococcosis mostly caused by C. neoformans continues to occur predominantly in HIV-infected adults despite HAART being widely distributed in Brazil. Cryptococcosis remains a significant opportunistic infection in solid organ transplant recipients. Despite adequate antifungal treatment and management of intracranial hypertension in a reference tertiary care hospital, mortality was high. Identification of risk factors and additional treatment modalities, especially for intracranial hypertension, are necessary to improve care for patients with cryptococcal meningitis. 1. Introduction Cryptococcal meningitis may be the presenting manifestation of AIDS. The most common sites of occurrence of this infection are the central nervous system and the lungs [1–3]. Inhalation of cryptococcal particles from contaminated soil into the lung is considered the usual route of human infection. This organism disseminates hematogenously, and it has a propensity to localize in the central nervous system, causing meningoencephalitis [2]. Although the incidence of cryptococcal meningitis has declined in the HIV patients who undergo antiretroviral therapy, cryptococcal disease remains a leading cause of mortality in the developing world [4, 5]. The clinical signs and symptoms of C. neoformans meningitis are indistinguishable from those of many other causes of meningitis, especially tubercular meningitis. An 2 Canadian Journal of Infectious Diseases and Medical Microbiology early diagnosis of the cryptococcal infection is therefore necessary for its appropriate management. A reduction in the rate of opportunistic infections and hospitalizations in adults infected with AIDS after HAART intervention is well documented in countries with universal access to antiretrovirals [6]. The present work is a retrospective study of patients with cryptococcal meningitis admitted to a Brazilian tertiary care hospital 23 years after the introduction of HAART in Brazil. 2. Materials and Methods This retrospective analysis of epidemiological and clinical data from patients with meningeal cryptococcosis was performed during the period of January 2009 to December 2016 in a tertiary care hospital in southern Brazil. Cryptococcal meningitis was confirmed by a positive CSF cryptococcal culture and/or cryptococcal antigen test. The medical records of all eligible patients were reviewed, and data regarding demographics, medical history, clinical and laboratory characteristics, treatment regimens, and clinical outcomes were collected. Patients were evaluated for risk factors and mortality. 2.1. Statistical Analysis. Data were analyzed using SPSS software, version 18 or superior. Results were expressed in mean and standard deviation or median and interquartile range for variables in numeric scale and number and percentage for variables in nominal scale. Qualitative variables were compared by the chi-square test, Fisher’s exact test, or McNemar test, when indicated. For determination of the factors associated with overall, 30- and 60-day mortalities, multivariate logistic regression models were constructed using a stepwise regression. A predictive modeling strategy was used in which variables were selected based on the association with mortality in univariate analysis (using a p value ≤ 0.20) and retained if they significantly improved model fit. The Cox regression model was used for determination of risk factors associated with overall mortality. A Poisson regression model with robust variance was employed for determination of risk factors associated with mortality at 30 and 60 days. The Kaplan–Meier survival method was adopted for survival analysis of cohort. The survival between groups (HIV and non-HIV) was compared by log-rank test. For statistical significance, a p value ≤ 0.05 was considered. 3. Results As shown in Table 1, seventy-nine cases of cryptococcal meningitis were identified. Most of the patients presented positive CSF cultures for Cryptococcus neoformans (96%). The prevalence of males and females (...truncated)