scholarly journals Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update

2013 ◽  
Vol 14 (2) ◽  
pp. 76-86 ◽  
Author(s):  
The Southern African HIV Clinicians Society
Keyword(s):  
South Africa ◽  
Antiretroviral Therapy ◽  
Intracranial Pressure ◽  
Amphotericin B ◽  
Opportunistic Infection ◽  
Cryptococcal Meningitis ◽  
Laboratory Diagnosis ◽  
First Episode ◽  
Raised Intracranial Pressure ◽  
Amphotericin B Deoxycholate

Six years after the first Society guidelines were published, cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among HIV-infected adults in South Africa. Several important developments have spurred the  publication of updated guidelines to manage this common fungal opportunistic infection. Recommendations described here include: (1) screening and pre-emptive treatment; (2) laboratory diagnosis and monitoring; (3) management of a first episode of CM; (4) amphotericin B deoxycholate toxicity prevention, monitoring and management; (5) timing of antiretroviral therapy among patients with CM; (6) management of raised intracranial pressure; (7) management of relapse episodes of CM.

scholarly journals Prevalence and Hospital Management of Amphotericin B Deoxycholate-Related Toxicities during Treatment of HIV-Associated Cryptococcal Meningitis in South Africa

2016 ◽  
Vol 10 (7) ◽  
pp. e0004865 ◽  
Author(s):  
Susan Meiring ◽  
Melony Fortuin-de Smidt ◽  
Ranmini Kularatne ◽  
Halima Dawood ◽  
Nelesh P. Govender ◽  
...  
Keyword(s):  
South Africa ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Hospital Management ◽  
Amphotericin B Deoxycholate

scholarly journals Population Pharmacokinetic Model and Meta-analysis of Outcomes of Amphotericin B Deoxycholate Use in Adults with Cryptococcal Meningitis

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Katharine E. Stott ◽  
Justin Beardsley ◽  
Sarah Whalley ◽  
Freddie Mukasa Kibengo ◽  
Nguyen Thi Hoang Mai ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Rate Constant ◽  
Cryptococcal Meningitis ◽  
Drug Exposure ◽  
Meta Analysis ◽  
Central Compartment ◽  
Order Rate Constant ◽  
Peripheral Compartment ◽  
First Order ◽  
Amphotericin B Deoxycholate

ABSTRACT There is a limited understanding of the population pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAmB) for cryptococcal meningitis. A PK study was conducted in n = 42 patients receiving DAmB (1 mg/kg of body weight every 24 h [q24h]). A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of treatment of cryptococcal meningitis patients with DAmB monotherapy, and a meta-analysis was performed. The PK parameter means (standard deviations) were as follows: clearance, 0.03 (0.01) × weight + 0.67 (0.01) liters/h; volume, 0.82 (0.80) × weight + 1.76 (1.29) liters; first-order rate constant from central compartment to peripheral compartment, 5.36 (6.67) h−1; first-order rate constant from peripheral compartment to central compartment, 9.92 (12.27) h−1. The meta-analysis suggested that the DAmB dosage explained most of the heterogeneity in cerebrospinal fluid (CSF) sterility outcomes but not in mortality outcomes. Simulations of values corresponding to the area under concentration-time curve from h 144 to h 168 (AUC144–168) resulted in median (interquartile range) values of 5.83 mg · h/liter (4.66 to 8.55), 10.16 mg · h/liter (8.07 to 14.55), and 14.51 mg · h/liter (11.48 to 20.42) with dosages of 0.4, 0.7, and 1.0 mg/kg q24h, respectively. DAmB PK is described adequately by a linear model that incorporates weight with clearance and volume. Interpatient PK variability is modest and unlikely to be responsible for variability in clinical outcomes. There is discordance between the impact that drug exposure has on CSF sterility and its impact on mortality outcomes, which may be due to cerebral pathology not reflected in CSF fungal burden, in addition to clinical variables.

Cost-effectiveness and budget impact of flucytosine as induction therapy in the treatment of cryptococcal meningitis in HIV-infected adults in South Africa

2020 ◽  
Author(s):  
Jacqui Miot ◽  
Trudy Leong ◽  
Simbarashe Takuva ◽  
Andrew Parrish ◽  
Halima Dawood
Keyword(s):  
South Africa ◽  
Cost Effectiveness ◽  
Amphotericin B ◽  
Induction Therapy ◽  
Cryptococcal Meningitis ◽  
Budget Impact ◽  
Cost Effective ◽  
Standard Of Care ◽  
Sub Saharan Africa ◽  
Oral Regimen

Abstract Background Cryptococcal meningitis in HIV-infected patients in sub-Saharan Africa accounts for three-quarters of the global cases and 135 000 deaths per annum. Current treatment includes the use of fluconazole and amphotericin B. Recent evidence has shown that the synergistic use of flucytosine improves efficacy and reduces toxicity, however affordability and availability has hampered access to flucytosine in many countries. This study investigated the evidence and cost implications of introducing flucytosine as induction therapy for cryptococcal meningitis in HIV-infected adults in South Africa. Methods A decision analytic cost-effectiveness and budget impact model was developed based on survival estimates from the ACTA trial and local costs for flucytosine as induction therapy in HIV-infected adults with cryptococcal meningitis in a public sector setting in South Africa. The model considered four treatment arms: (a) standard of care; 2-week course of amphotericin B/fluconazole (2wk AmBd/Flu), (b) 2-week course of amphotericin B/flucytosine (2wk AmBd/5FC), (c) short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC) and (d) oral course; 2-week oral fluconazole/flucytosine (oral). A sensitivity analysis was conducted on key variables. Results The highest total treatment costs were in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, then the 1-week AmBd/5FC with the lowest cost in the standard of care arm. Compared to standard of care the 1-week flucytosine course is most cost-effective at USD31/QALY, followed by the oral 2-week course at USD155/QALY and the 2-week flucytosine course at USD568/QALY. The budget impact analysis shows that the 1-week course has the lowest incremental cost, followed by the oral course and then the 2-week flucytosine course compared to what is currently spent on standard of care. Sensitivity analyses suggest that the model is most sensitive to the price of flucytosine and hospital costs, particularly length of stay. Conclusions The addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective regardless of whether it is used as a 1-week, 2-week or oral regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Aline Z. de Azambuja ◽  
Gustavo Wissmann Neto ◽  
Guilherme Watte ◽  
Luciana Antoniolli ◽  
Luciano Z. Goldani
Keyword(s):  
Risk Factors ◽  
Intracranial Hypertension ◽  
Amphotericin B ◽  
Opportunistic Infection ◽  
Cryptococcal Meningitis ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Clinical Manifestations ◽  
Care Hospital ◽  
Southern Brazil

Objective.Cryptococcus neoformansis 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 forCryptococcus 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 byC. neoformanscontinues 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.

scholarly journals High Mortality in HIV-Associated Cryptococcal Meningitis Patients Treated With Amphotericin B–Based Therapy Under Routine Care Conditions in Africa

2018 ◽  
Vol 5 (11) ◽  
Author(s):  
Raju K K Patel ◽  
Tshepo Leeme ◽  
Caitlin Azzo ◽  
Nametso Tlhako ◽  
Katlego Tsholo ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Treatment Guidelines ◽  
Routine Care ◽  
Outcome Data ◽  
High Dose ◽  
Recommended Treatment ◽  
Amphotericin B Deoxycholate ◽  
Intravenous Amphotericin

Abstract Background Cryptococcal meningitis (CM) causes 10%–20% of HIV-related deaths in Africa. Due to limited access to liposomal amphotericin and flucytosine, most African treatment guidelines recommend amphotericin B deoxycholate (AmB-d) plus high-dose fluconazole; outcomes with this treatment regimen in routine care settings have not been well described. Methods Electronic national death registry data and computerized medical records were used to retrospectively collect demographic, laboratory, and 1-year outcome data from all patients with CM between 2012 and 2014 at Botswana’s main referral hospital, when recommended treatment for CM was AmB-d 1 mg/kg/d plus fluconazole 800 mg/d for 14 days. Cumulative survival was estimated at 2 weeks, 10 weeks, and 1 year. Results There were 283 episodes of CM among 236 individuals; 69% (163/236) were male, and the median age was 36 years. All patients were HIV-infected, with a median CD4 count of 39 cells/mm3. Two hundred fifteen person-years of follow-up data were captured for the 236 CM patients. Complete outcome data were available for 233 patients (99%) at 2 weeks, 224 patients (95%) at 10 weeks, and 219 patients (93%) at 1 year. Cumulative mortality was 26% (95% confidence interval [CI], 20%–32%) at 2 weeks, 50% (95% CI, 43%–57%) at 10 weeks, and 65% (95% CI, 58%–71%) at 1 year. Conclusions Mortality rates following HIV-associated CM treated with AmB-d and fluconazole in a routine health care setting in Botswana were very high. The findings highlight the inadequacies of current antifungal treatments for HIV-associated CM and underscore the difficulties of administering and monitoring intravenous amphotericin B deoxycholate therapy in resource-poor settings.

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