scholarly journals Randomized Comparison of Amphotericin B Deoxycholate Dissolved in Dextrose or Intralipid for the Treatment of AIDS-Associated Cryptococcal Meningitis

1996 ◽  
Vol 23 (3) ◽  
pp. 556-562 ◽  
Author(s):  
V. Joly ◽  
P. Aubry ◽  
A. Ndayiragide ◽  
I. Carriere ◽  
E. Kawa ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
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.

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.

scholarly journals Ambulatory induction phase treatment of cryptococcal meningitis in HIV integrated primary care clinics, Yangon, Myanmar

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Clare E. Warrell ◽  
Catriona Macrae ◽  
Alistair R. D. McLean ◽  
Edmund Wilkins ◽  
Elizabeth A. Ashley ◽  
...  
Keyword(s):  
Primary Care ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Integrated Primary Care ◽  
Induction Treatment ◽  
Induction Phase ◽  
Retrospective Case ◽  
Primary Care Clinics ◽  
Amphotericin B Deoxycholate ◽  
One Year

Abstract Background Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. Method This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7–1.0 mg/kg) and oral fluconazole (800 mg orally/day). Results Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. Conclusion Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.

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.

HIV-Associated Cryptococcal Meningitis Patients Treated with Amphotericin B Deoxycholate Plus Flucytosine under Routine Care Conditions in a Referral Center in São Paulo, Brazil

2020 ◽  
Vol 186 (1) ◽  
pp. 93-102
Author(s):  
José E. Vidal ◽  
Camila de Albuquerque Moraes ◽  
Renata Elisie Barbalho de Siqueira ◽  
Nathalya Fernanda Brito Miranda ◽  
Rosa Marcusso ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Routine Care ◽  
Sao Paulo ◽  
São Paulo ◽  
Referral Center ◽  
Amphotericin B Deoxycholate

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 Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis

2015 ◽  
Vol 59 (12) ◽  
pp. 7224-7231 ◽  
Author(s):  
Tihana Bicanic ◽  
Christian Bottomley ◽  
Angela Loyse ◽  
Annemarie E. Brouwer ◽  
Conrad Muzoora ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Induction Treatment ◽  
Standardized Protocol ◽  
Short Course ◽  
Amphotericin B Deoxycholate ◽  
Intravenous Saline ◽  
Electrolyte Replacement ◽  
Grade Iii ◽  
Electrolyte Abnormalities

ABSTRACTAmphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3;P= 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11;P= 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.

scholarly journals Efficacy of an Abbreviated Induction Regimen of Amphotericin B Deoxycholate for Cryptococcal Meningoencephalitis: 3 Days of Therapy Is Equivalent to 14 Days

mBio ◽  
2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Joanne Livermore ◽  
Susan J. Howard ◽  
Andrew D. Sharp ◽  
Joanne Goodwin ◽  
Lea Gregson ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Induction Therapy ◽  
Cryptococcal Meningitis ◽  
Standard Of Care ◽  
Experimental Period ◽  
Antifungal Effect ◽  
Cryptococcal Meningoencephalitis ◽  
Drug Of Choice ◽  
Days Of Therapy ◽  
Amphotericin B Deoxycholate

ABSTRACT Cryptococcal meningoencephalitis is an urgent global health problem. Induction regimens using 14 days of amphotericin B deoxycholate (dAmB) are considered the standard of care but may not be suitable for resource-poor settings. We investigated the efficacy of conventional and abbreviated regimens of dAmB for cryptococcal meningoencephalitis in both murine and rabbit models of cryptococcal meningoencephalitis. We examined the extent to which immunological effectors contribute to the antifungal effect. We bridged the results to humans as a first critical step to define regimens suitable for further study in clinical trials. There were significant differences in the murine plasma-versus-cerebrum dAmB concentration-time profiles. dAmB was detectable in the cerebrum throughout the experimental period, even following the administration of only three doses of 3 mg/kg. dAmB induced a fungistatic effect in the cerebrum with a 2- to 3-log10 CFU/g reduction compared with controls. The effect of 3 days of therapy was the same as that of daily therapy for 14 days. There was no evidence of increased numbers of CD3+ CD4+ or CD3+ CD8+ cells in treated mice to account for the persistent antifungal effect of an abbreviated regimen. The administration of dAmB at 1 mg/kg/day for 3 days was the same as daily therapy in rabbits. The bridging studies suggested that a human regimen of 0.7 mg/kg/day for 3 days resulted in nearly maximal antifungal activity in both the cerebrum and cerebrospinal fluid. An abbreviated regimen (3 days of therapy) of dAmB appears to be just as effective as conventional induction therapy for cryptococcal meningoencephalitis. IMPORTANCE Cryptococcal meningitis is a significant and neglected infection that is associated with excessive morbidity and mortality. In well-resourced health care settings, induction therapy with at least 2 weeks of amphotericin B deoxycholate (dAmB) is advocated. Multiple clinical studies suggest that dAmB is the drug of choice for cryptococcal meningitis. In many parts of the world where the burden of cryptococcal meningitis is highest, it is infeasible to administer dAmB for prolonged periods. This paper provides the experimental basis for the efficacy of abbreviated regimens of dAmB for cryptococcal meningitis. The concept was explored in two well-validated laboratory animal models of cryptococcal meningitis, and the results were bridged to humans by using a range of mathematical modeling techniques. A 3-day regimen is as effective as the standard 14-day course. An abbreviated regimen is significantly more feasible and may enable better antifungal therapy to be administered to many patients with this frequently lethal disease.

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