Fungal Burden, Early Fungicidal Activity, and Outcome in Cryptococcal Meningitis in Antiretroviral-Naive or Antiretroviral-Experienced Patients Treated with Amphotericin B or Fluconazole

Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa.
Clinical Infectious Diseases (Impact Factor: 8.89). 08/2007; 45(1):76-80. DOI: 10.1086/518607
Source: PubMed


In a prospective observational study of 54 patients with human immunodeficiency virus-associated cryptococcal meningitis, the early fungicidal activity of amphotericin B (1 mg/kg/day) was significantly greater than that of fluconazole (400 mg/day). Compared with antiretroviral therapy-naive patients, patients developing cryptococcal meningitis while already receiving antiretroviral therapy had lower baseline fungal burdens and a longer median duration of survival, but there were no differences observed in fungal clearance, cerebrospinal fluid proinflammatory cytokines, or 10-week mortality.

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    • "Although the disease affects mainly the immunosuppressed host either in HIV-infected or non-HIV-infected (largely iatrogenic immunosuppression for organ transplant or chronic inflammatory conditions) patients, it can also occur in the immunocompetent host, particularly in China and Australia (Chen et al., 2013; Zhu et al., 2010). As a general rule, the ART-naïve HIV patient has a high fungal burden with a paucity of inflammation, whilst non-HIV patients and HIV patients presenting post-ART have lower fungal burdens with more CSF inflammation (Bicanic et al., 2007; Bratton et al., 2013). Immunopathology can also vary over time within the same host following restoration of immune function. "
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    ABSTRACT: Cryptococcosis has evolved into a major invasive fungal disease over the last century. Its primary epidemiology has been focused on three major outbreaks of disease that reflects both changing environmental exposures and growth of host risk factors. The molecular understandings of yeast pathobiology have been bolstered by identification of the yeast’s dynamic genomic structures and functions. It is during these new insights into epidemiology and pathobiology that we have also improved our diagnosis of this infection with a new point-of-care, simple, cheap test which utilizes a lateral flow assay for antigen detection. With methods for effective identification of Cryptococcus in the host, the principles for management of this deadly infection include both use of old drugs and new insights into treatment strategies to improve outcome. In this review there are a series of recent insights, opinions, and facts which attempt to summarize our present knowledge base for this deadly fungal central nervous system infection with a particular emphasis on its diagnosis and management.
    Fungal Genetics and Biology 10/2014; 301. DOI:10.1016/j.fgb.2014.10.003 · 2.59 Impact Factor
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    • "This extended time to diagnosis possibly accounts for the higher mortality at 90 days, but we suspect the differences in one-year mortality are due to the NHNT patients’ other underlying diseases. Considering the 71 immunocompromised NHNT patients and excluding the 39 individuals with no identifiable immunodeficiency, we found that 90-day mortality was 35% (25/71), which approximated research settings in sub-Saharan Africa (24–37%) [17], [18]. These findings were also consistent with recent retrospective data from a smaller U.S. cohort that found 37% mortality among NHNT patients whose mean duration of symptoms was longer than the comparator groups of HIV-positive patients and OTRs [19]. "
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    ABSTRACT: Cryptococcosis 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. We 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. We 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. Predictors 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.
    PLoS ONE 03/2013; 8(3):e60431. DOI:10.1371/journal.pone.0060431 · 3.23 Impact Factor
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    • "The in-hospital mortality rates for cryptococcal meningitis also remain high despite recent improvements in access to high-dose intravenous fluconazole and cryptococcal antigen testing [8,9,21]. Although patients were diagnosed and initiated on fluconazole within 24 hours of presentation to our hospital, the mortality rate remained close to 70%, comparable with rates reported by others in sub-Saharan Africa [2,10,11]. "
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    ABSTRACT: Cryptococcal meningitis is a leading cause of death among HIV-infected individuals in sub-Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre-emptive treatment. In this study, we describe the impact of screening HIV-positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital. All adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV-positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in-hospital mortality were recorded. Of 333 HIV-infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in-hospital deaths. Despite screening of all HIV-positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high-dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in-hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre-emptive treatment for high-risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed.
    Journal of the International AIDS Society 10/2011; 14(1):48. DOI:10.1186/1758-2652-14-48 · 5.09 Impact Factor
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