Mortality In Cryptococcal Meningitis Research Articles

Analysis of the relationship between drug susceptibility of Cryptococcus neoformans isolates and mortality in HIV-negative cryptococcal meningitis

ObjectivesThe relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood. MethodsWe conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year. ResultsAll of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality. ConclusionMost Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.

Impact of prior cryptococcal antigen screening on in-hospital mortality in cryptococcal meningitis or fungaemia among HIV-seropositive individuals in South Africa: a cross-sectional observational study

ObjectivesWe investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital. MethodsWe compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/μL and laboratory-confirmed CM/fungaemia from 2017–2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre–COVID-19: before March 2020 vs. COVID-19: after March 2020). ResultsOverall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69–0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47–0.87]; p = 0.005) compared with before (OR, 0.95 [0.76–1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51–0.96]; p = 0.03). DiscussionPrevious CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier.

Early Antiretroviral Therapy Not Associated With Higher Cryptococcal Meningitis Mortality in People With Human Immunodeficiency Virus in High-Income Countries: An International Collaborative Cohort Study.

Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings. Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an RCT comparing the effects of early (within 14 days of CM) and late (14-56 days after CM) ART on all-cause mortality, adjusting for potential confounders. Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33-44) years; the median CD4+ T-cell count, 19/μL (10-56/μL); and median HIV viral load, 5.3 (4.9-5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval, .64-2.56) and 1.40 (.66-2.95), respectively. We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide.

Prevalence of neuroinfectious diseases and outcomes in Africa

Prevalence of neuroinfectious diseases and outcomes in Africa

Clinical Characteristics and Risk Factors for Mortality in Cryptococcal Meningitis: Evidence From a Cohort Study.

IntroductionDespite advances in the diagnosis and management, cryptococcal meningitis (CM) is still associated with high mortality due to insufficient knowledge about clinical characteristics and risk factors for poor outcomes. The aim of the present study is to provide additional evidence for regarding clinical characteristics, diagnosis, and factors associated with increased risk of mortality in CM patients.MethodsIn this cohort study, we included eligible patients consecutively admitted to West China Hospital between January 2009 and December 2018. The clinical characteristics and diagnosis method of cerebrospinal fluid culture and India ink stain were analyzed. Independent risk factors were identified by a multivariable logistic regression.ResultsA total of 186 CM patients were included in the analysis. After a 1-year follow-up, 63 patients had died. Headache is the most common presenting symptom (97.3%), followed by vomiting (72%), fever (71.5%), altered consciousness (45.7%), abnormal vision (32.8%), and seizure (15.1%). Older age, altered consciousness or seizures, lower white blood cell count or total protein in cerebrospinal fluid (CSF), and unidentified CSF cryptococcal antigen (CrAg) are all factors associated with increasing risk of death (P < 0.05). We also found a dose-dependent trend between the number of symptoms and risk of death (trend p < 0.001). Multivariate logistic regression revealed that age (P = 0.004, OR = 1.042, 95% CI 1.013–1.071), seizure (P = 0.025, OR = 3.105, 95% CI 1.152–8.369), altered consciousness (P < 0.001, OR=6.858, 95% CI 3.063–15.38), and unidentified CSF CrAg are the independent prognostic factors. In addition, we observed that diagnosis of 28.5% and 22.5% CM could not be established by a single testing of CSF India ink stain or culture, respectively. Use of multiple testing methods or combination of the two assays increases the detection rate.ConclusionOur data show that older age, seizures, altered consciousness, and an inability to detect CSF CrAg are the independent risk factors of death within 1 year in CM patients. Moreover, we recommend use of multiple testing methods with CSF culture and India ink stain. Combined testing with both assays should be considered for initial CM diagnosis.

The prevalence and mortality of cryptococcal meningitis in patients with autoimmune diseases: a systematic review and meta-analysis.

Growing evidence suggests that autoimmune diseases (AIDs) are risk factors for cryptococcal meningitis (CM). Therefore, understanding the epidemiological and clinical profile of CM in patients with AIDs is important. This meta-analysis assessed the prevalence, clinical profiles, and clinical outcomes of CM in AIDs.Studies on CM in patients with AIDs were searched for in PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure, and meta-analyses were performed using the statistical program of R.Nineteen studies with 36,631 patients with AIDs were analyzed. The overall pooled CM prevalence was 0.4% (95% confidence interval [CI], 0.3-0.6%), 90.7% of which occurred in female patients. Thirteen studies with 77 patients with AIDs diagnosed with CM were analyzed, and the mortality rate was 26.7% (95% CI, 9.5-47.2%). Of patients with systemic lupus erythematosus, 30.1% of CM cases were initially misdiagnosed (95% CI, 0-65.6%). The primary symptom of CM with AIDs was headache (99.4%; 95% CI, 92.1-100%), followed by fever (93.7%; 95% CI, 82.8-100%) and vomiting (37.2%; 95% CI, 13.2-61.2%).The prevalence of CM infections among patients with AIDs should not be underestimated despite non-specific clinical presentations as there were fatal outcomes. Our results suggest that more research is needed to understand the relationship between AIDs and CM, and clinical trials are necessary to improve treatment strategies.

Three-year mortality in cryptococcal meningitis: Hyperglycemia predict unfavorable outcome.

Existing evidence revealed grave prognosis for cryptococcal meningitis (CM), particularly its short-term mortality. However, its long-term survival and prognostic factors remained unknown. This study investigated 3-year mortality and analyzed its predictive factors in patients with CM. This retrospective cohort study with 83 cerebrospinal fluid culture-confirmed CM patients was conducted at China Medical University Hospital from 2003 to 2016. The 3-year mortality rate in patients with CM was 54% (45 deaths among 83 patients). Advanced age, human immunodeficiency virus (HIV) seronegative state, low Glasgow Coma Scale score on admission, decreased hemoglobin and hyperglycemia on diagnosis were associated with 3-year mortality. After multivariate adjustment in the Cox proportional hazard model, only severe hyperglycemia (serum glucose ≥200 mg/dL) on diagnosis could predict 3-year mortality.

Delays in lumbar puncture are independently associated with mortality in cryptococcal meningitis: a nationwide study

Background Cryptococcal meningitis (CM) is the most serious presentation of invasive cryptococcosis. Seen in patients with and without HIV infection, CM is associated with significant morbidity and mortality. Early lumbar puncture is a cornerstone of treatment in cryptococcal meningitis. We present findings from a nationwide analysis of patients admitted with CM in the United States between 2007 and 2016, with the aim of determining the impact of delays in lumbar puncture on inpatient outcomes. Methods The national inpatient sample (NIS) database was queried for all inpatient visits for cryptococcal meningitis between January 2007 and December 2016. Logistic regression models were used to determine risk factors for inpatient mortality, prolonged admissions, and delays in obtaining an initial lumbar puncture. Results The annual number of admissions for CM decreased during the study interval, from 3590 in 2007 to 2830 in 2016. Mortality did not change over this period (9.9%); however, length of stay and inpatient cost significantly increased. The proportion of patients with HIV declined from 70.7% to 54.0%. Delay in lumbar puncture beyond the first 24 h was independently associated with mortality (OR = 1.55, CI = 1.31–1.82, p-value <.001). Patients admitted on a weekend, those of African–American ethnicity, and those without a known history of HIV were more likely to have delays in obtaining an early LP. HIV patients had a lower risk of mortality (OR = 0.77, CI = 0.68–0.86, p-value <.001). Conclusion We found an independent association of delay in early lumbar puncture with worsened patient outcomes. Inpatient mortality for patients with CM continues to remain high, with an increasing proportion of patients without underlying HIV infection. There were significant deviations in management of CM from Infectious Diseases Society of America (IDSA) guidelines.

Impact of biological sex on cryptococcal meningitis mortality in Uganda and South Africa.

We examined the role of biological sex in cryptococcal meningitis mortality in a large cohort. Our findings reveal significant differences in inflammatory markers by biological sex. Women have significantly higher mortality due to cryptococcal meningitis that is attributable to anemia at baseline.

Cerebrospinal Fluid Lactate as a Prognostic Marker of Disease Severity and Mortality in Cryptococcal Meningitis.

Cerebrospinal fluid (CSF) lactate levels can be used to differentiate between bacterial and viral meningitis. We measured CSF lactate in individuals with cryptococcal meningitis to determine its clinical significance. We measured point-of-care CSF lactate at the bedside of 319 Ugandan adults living with human immunodeficiency virus at diagnosis of cryptococcal meningitis. We summarized demographic variables and clinical characteristics by CSF lactate tertiles. We evaluated the association of CSF lactate with clinical characteristics and survival. Individuals with high CSF lactate >5 mmol/L at cryptococcal diagnosis more likely presented with altered mental status (P < .0001), seizures (P = .0005), elevated intracranial opening pressure (P = .03), higher CSF white cells (P = .007), and lower CSF glucose (P = .0003) compared with those with mid-range (3.1 to 5 mmol/L) or low (≤3 mmol/L) CSF lactate levels. Two-week mortality was higher among individuals with high baseline CSF lactate >5 mmol/L (35%; 38 of 109) compared with individuals with mid-range (22%; 25 of 112) or low CSF lactate (9%; 9 of 97; P =<.0001). After multivariate adjustment, CSF lactate >5 mmol/L remained independently associated with excess mortality (adjusted hazard ratio = 3.41; 95% confidence interval, 1.55-7.51; P = .002). We found no correlation between baseline CSF lactate levels and blood capillary lactate levels. Baseline point-of-care CSF lactate levels are a prognostic marker of disease severity and mortality in cryptococcal meningitis. Individuals with an elevated baseline CSF lactate level are more likely to present with altered mental status, seizures, and elevated CSF opening pressure and are at a greater risk of death. Future studies are needed to determine targeted therapeutic management strategies in persons with high CSF lactate.

Cerebrospinal Fluid Early Fungicidal Activity as a Surrogate Endpoint for Cryptococcal Meningitis Survival in Clinical Trials.

In cryptococcal meningitis phase 2 clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The Food and Drug Administration allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18 weeks. We pooled individual-level CSF data from 3 sequential cryptococcal meningitis clinical trials conducted during 2010-2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony-forming units (CFUs) per mL CSF were analyzed by general linear regression versus day of culture over the first 10 days. Mortality through 18 weeks was 37% for EFA > = 0.60 (n = 170), 36% for 0.40-0.59 (n = 182), 39% for 0.30-0.39 (n = 112), 35% for 0.20-0.29 (n = 87), and 50% for those with EFA < 0.20 CFU/mL/day (n = 187). The hazard ratio for 18-week mortality, comparing those with EFA < 0.20 to those with EFA > = 0.20, was 1.60 (95% confidence interval, 1.25, 2.04; P = .002). The lowest EFA group had lower median CD4 T-cell counts (P < .01) and lower proportion of patients with CSF pleocytosis (P < .001). EFA is associated with all-cause mortality in cryptococcal meningitis. An EFA threshold of > = 0.20 log10 CFU/mL/day was associated with similar 18-week mortality (37%) compared to 50% mortality with EFA < 0.20. This EFA threshold may be considered a target for a surrogate endpoint. This builds upon existing studies to validate EFA as a surrogate endpoint.

Increased cryptococcal meningitis mortality among HIV negative, non-transplant patients: a single US center cohort study.

Cryptococcal meningitis (CM) is an opportunistic fungal infection associated with human immunodeficiency virus (HIV) and other forms of immunosuppression. We lack a clear understanding of CM associated mortality among HIV-negative, non-transplant patients in the United States (US). This article compares clinical features and outcomes across HIV status in patients with laboratory-confirmed CM.Methods:A retrospective cohort study was performed that included adult patients with laboratory-confirmed CM treated at an academic tertiary hospital between January 2000 and September 2018. Those with a history of organ transplant or non-meningeal infections were excluded. Data were gathered on demographics, HIV status, clinical presentation, cerebrospinal fluid (CSF) profiles, neurological outcomes, hospital course, and mortality.Results:A total of 70 patients with cryptococcal disease were identified. Our final sample included 36 CM patients, mean age was 48.8 ± 13.2 years; of this group, 66.7% (n = 24) had HIV. Median [interquartile range (IQR)] absolute CD4 count for the HIV group was 35 cells/μl (10–80 cells/μl). Non-HIV/non-transplant patients were significantly older (p < 0.001) and had higher rates of altered mental status (AMS) on presentation (58.3% versus 25%, p = 0.05). Non-HIV patients/non-transplant patients had significantly higher CSF white blood cell (WBC) count (p = 0.02), lower CSF glucose (p = 0.005), and higher CSF protein (p < 0.001) compared with HIV patients. There was no significant variation in temperature, blood pressure, WBC count, serum sodium, CSF opening pressure, length of stay, intensive care unit admission, or neurological outcomes. Overall, 90-day all-cause mortality was 19.4%: mortality rates were significantly higher in non-HIV/non-transplant patients at both 90 days (41.7% versus 8.3%, p = 0.017) and 1 year (41.7% versus 12.5%, p = 0.047).Conclusion:Compared with HIV-infected individuals, non-HIV/non-transplant CM patients have a higher CSF WBC count at the time of diagnosis, higher rates of AMS on presentation, and higher rates of 90-day and 1-year all-cause mortality. Further prospective research is needed to identify the hallmarks of CM in non-HIV/non-transplant patients to facilitate early identification and intervention.

Cytomegalovirus Viremia Associated With Increased Mortality in Cryptococcal Meningitis in Sub-Saharan Africa.

Cryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Cytomegalovirus (CMV) viremia may be associated with increased mortality in persons living with HIV who have tuberculosis. It is unknown whether concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections. We prospectively enrolled Ugandans living with HIV who had cryptococcal meningitis from 2010-2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival rates among those with and without CMV viremia. Of 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL, interquartile range [IQR] 259-2390). All samples tested were positive on immunoglobin G serology. The median CD4+ T cell count was 19 cells/µL (IQR 9-70) and did not differ by the presence of CMV viremia (P = .47). The 10-week mortality rates were 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (hazard ratio 2.19, 95% confidence interval [CI] 1.07-4.49; P = .03), which remained significant after a multivariate adjustment for known risk factors of mortality (adjusted hazard ratio 3.25, 95% CI 1.49-7.10; P = .003). Serum and cerebrospinal fluid cytokine levels were generally similar and cryptococcal antigen-specific immune stimulation responses did not differ between groups. Half of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with an over 2-fold higher mortality rate. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect an underlying immune dysfunction (ie, cause vs effect). NCT01075152.

Epidemiology and aetiologies of cryptococcal meningitis in Africa, 1950–2017: protocol for a systematic review

IntroductionCryptococcal meningitis is a neglected disease and an AIDS-defining illness, responsible for 15% of all AIDS-related deaths globally. In 2014, the estimated number of incident cryptococcal meningitis cases was 223...

Chapter 11 - Cryptococcal meningitis in AIDS

Cryptococcal meningitis remains a significant cause of morbidity and mortality amongst patients living with human immunodeficiency virus (HIV). The prevalence in the developed world has decreased as HIV is being diagnosed earlier, but is still significant, and the prevalence in resource-limited settings is exceedingly high. The presenting symptoms usually include a headache, fever, and, less often, cranial nerve abnormalities. Space-occupying lesions do occur, but are rare. Once diagnosed, patients should be treated with a combination of amphotericin and flucytosine, with step-down therapy to fluconazole for a minimum of a year, or until the CD4 count is above 100 cells/μL, whichever is longer. In the acute phase of treatment increased opening pressure is common, which should be managed aggressively with frequent lumbar punctures, or through neurosurgical interventions (lumbar drains, ventriculoperitoneal shunts) if those fail. Antiretrovirals should be delayed at least 2 weeks, but maybe as many as 10 weeks, after initiation of antifungal therapy in order to prevent clinical or subclinical immune reconstitution inflammatory syndrome (IRIS), which may lead to increased mortality. However, if IRIS does develop, there is no role for antiretroviral interruption, and the condition should be managed supportively by use of anti-inflammatories and aggressive management of elevated opening pressure, if present. Steroids should be administered for specific indications only (IRIS or cryptococcoma with cerebral edema and risk of herniation) as routine use of steroids increases mortality in cryptococcal meningitis.

Early Fungicidal Activity as a Candidate Surrogate Endpoint for All-Cause Mortality in Cryptococcal Meningitis: A Systematic Review of the Evidence.

BackgroundCryptococcal meningitis (CM) is a leading cause of HIV-associated mortality. In clinical trials evaluating treatments for CM, biomarkers of early fungicidal activity (EFA) in cerebrospinal fluid (CSF) have been proposed as candidate surrogate endpoints for all- cause mortality (ACM). However, there has been no systematic evaluation of the group-level or trial-level evidence for EFA as a candidate surrogate endpoint for ACM.MethodsWe conducted a systematic review of randomized trials in treatment of CM to evaluate available evidence for EFA measured as culture negativity at 2 weeks/10 weeks and slope of EFA as candidate surrogate endpoints for ACM. We performed sensitivity analysis on superiority trials and high quality trials as determined by Cochrane measures of trial bias.ResultsTwenty-seven trials including 2854 patients met inclusion criteria. Mean ACM was 15.8% at 2 weeks and 27.0% at 10 weeks with no overall significant difference between test and control groups. There was a statistically significant group-level correlation between average EFA and ACM at 10 weeks but not at 2 weeks. There was also no statistically significant group-level correlation between CFU culture negativity at 2weeks/10weeks or average EFA slope at 10 weeks. A statistically significant trial-level correlation was identified between EFA slope and ACM at 2 weeks, but is likely misleading, as there was no treatment effect on ACM.ConclusionsMortality remains high in short time periods in CM clinical trials. Using published data and Institute of Medicine criteria, evidence for use of EFA as a surrogate endpoint for ACM is insufficient and could provide misleading results from clinical trials. ACM should be used as a primary endpoint evaluating treatments for cryptococcal meningitis.

Flow Cytometry To Assess Cerebrospinal Fluid Fungal Burden in Cryptococcal Meningitis.

Fungal burden in the cerebrospinal fluid is an important determinant of mortality in cryptococcal meningitis, but its use in aiding clinical decision making is hampered by the time involved to perform quantitative cultures. Here, we demonstrate the potential of flow cytometry as a novel and rapid technique to address this issue.

Comparisons of clinical features and mortality of cryptococcal meningitis between patients with and without human immunodeficiency virus infection

Cryptococcosis is a systemic infection caused by Cryptococcus neoformans, and cryptococcal meningitis can occur in patients with late-stage human immunodeficiency virus (HIV) infection and other forms of immunosuppressive status. This study was designed to compare clinical features and laboratory findings of cryptococcal meningitis in HIV-positive and HIV-negative patients. From January 1, 2000 to December 31, 2009, all patients aged more than 18 years hospitalized at National Taiwan University Hospital with a diagnosis of cryptococcal meningitis were analyzed retrospectively. In total, 88 patients with cryptococcal meningitis were identified and 37 (42%) were HIV infected. Cryptococcal meningitis occurred in young (mean, 38 vs. 60; p<0.001) and male (97% vs. 63%, p<0.001) populations more frequently among HIV-positive group with higher Charlson comorbidity score (mean, 7 vs. 4; p<0.001), higher initial complaint of cough (36% vs. 16%; p=0.032), lower cerebrospinal fluid (CSF) white count (mean, 26 vs. 86; p=0.024), lower total protein of the CSF (mean, 88 vs. 149; p=0.012), higher percentage of serum latex agglutination cryptococcal antigen titer exceeding 1:512 (77% vs. 50%; p=0.026), more extraneural involvement (70% vs. 49%; p=0.046), more cryptococcemia (68% vs. 35%; p=0.003), and higher proportion of normal brain images (44% vs. 13%; p=0.003) than HIV-negative group. The all-cause mortality rates on Day 30 and Day 90 were 23.9% and 31.8%, respectively. The independent risk factors for Day 30 mortality were altered mental status, extraneural involvement, absence of lymphocyte predominance, and absence of leptomeningeal enhancement (odds ratio: 7.84, 9.71, 0.22, and 0.07, respectively; 95% confidence interval): 2.03-30.27, 2.01-46.94, 0.06-0.80, and 0.01-0.49, respectively). Those for Day 90 mortality were serum white count more than 11,000/μL, higher Charlson comorbidity score, and absence of normal brain images (odds ratio: 5.39, 1.40, and 0.09, respectively; 95% confidence interval: 1.22-23.72, 1.11-1.76, and 0.01-0.78, respectively). The clinical features of cryptococcal meningitis between HIV and non-HIV patients have some divergences, including age, sex, underlying diseases, CSF parameters, extraneural site involvement, fungemia, and so on. We also identified risk factors for mortality of this disease. However, the mortality of cryptococcal meningitis was not different in HIV-positive and HIV-negative patients in terms of Day 30 and Day 90 mortality.

Factors associated with mortality in cryptococcal meningitis

To investigate factors associated with mortality in non-AIDS patients with cryptococcal meningitis. We retrospectively reviewed 154 cases of non-HIV cryptococcal meningitis in a tertiary care hospital in China, from 1997 through 2007. The 1-year attributable mortality was 19.6% (28/143), and overall mortality was 28.7% (41/143). Advanced age (> or = 60 years), delay in diagnosis (> 4 months), hematologic malignancy, solid malignancy, altered mental status (coma, seizure, herniation), and CSF drainage or shunting were factors associated with increased death; factors associated with increased survival were amphotericin B based initial therapy and flucytosine containing therapy. In multivariate analysis, age > or = 60 years, the time from symptom onset to diagnosis > 4 months, coma, cerebral herniation, and non-amphotericin B based initial therapy were independently associated with increased overall mortality; factors independently associated with cause-specific mortality were time from symptom onset to diagnosis > 4 months, cerebral herniation and non-amphotericin B based initial therapy. A variety of factors were associated with mortality in non-AIDS cryptococcal meningitis. Amphotericin B based initial treatment was independently correlated to improved 1-year survival.