Short course amphotericin B with high dose fluconazole for HIV-associated cryptococcal meningitis

2012 ◽  
Vol 64 (1) ◽  
pp. 76-81 ◽  
Author(s):  
Conrad K. Muzoora ◽  
Taseera Kabanda ◽  
Giuseppina Ortu ◽  
John Ssentamu ◽  
Pasco Hearn ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
High Dose ◽  
Short Course

scholarly journals HIV-associated Cryptococcal Meningitis: a Review of Novel Short-Course and Oral Therapies

2020 ◽  
Vol 12 (4) ◽  
pp. 422-437
Author(s):  
Letumile R. Moeng ◽  
James Milburn ◽  
Joseph N. Jarvis ◽  
David S. Lawrence
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Liposomal Amphotericin ◽  
Phase Iii ◽  
Induction Treatment ◽  
High Dose ◽  
Ongoing Research ◽  
Short Course ◽  
Incidence And Mortality ◽  
The Impact

Abstract Purpose of review HIV-associated cryptococcal meningitis remains a significant public health problem in parts of Africa and Asia and a major cause of AIDS-related mortality, accounting for 15% of all AIDS-related deaths worldwide. Cryptococcal meningitis is uniformly fatal if untreated, and access to antifungal therapy in regions with the highest burden is often limited. Outcomes with fluconazole monotherapy are poor, and induction treatment with amphotericin B and high-dose fluconazole for 2 weeks is associated with significant drug-related toxicities and prolonged hospital admissions. This review focuses on the potential of novel short-course and oral combination therapies for cryptococcal meningitis. Recent findings Recent clinical trials have shown that shorter courses of amphotericin, if paired with oral flucytosine, rather than fluconazole, can achieve non-inferior mortality outcomes. In addition, an oral combination of fluconazole and flucytosine is a potential alternative. Liposomal amphotericin B may further simplify treatment; it is associated with fewer drug-related toxicities, and a recent phase II randomised controlled trial demonstrated that a single, high dose of liposomal amphotericin is non-inferior to 14 standard daily doses at clearing Cryptococcus from cerebrospinal fluid. This has been taken forward to an ongoing phase III, clinical endpoint study. Summary The incidence and mortality associated with cryptococcal meningitis is still unacceptably high. There is evidence supporting the use of short-course amphotericin B and oral combination antifungal treatment regimens for cryptococcal meningitis (CM). Ongoing research into short-course, high-dose treatment with liposomal amphotericin may also help reduce the impact of this devastating disease.

scholarly journals A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole, with short-course amphotericin B, for cryptococcal meningitis

AIDS ◽  
2012 ◽  
Vol 26 (11) ◽  
pp. 1363-1370 ◽  
Author(s):  
Arthur T. Jackson ◽  
Jesse C. Nussbaum ◽  
Jacob Phulusa ◽  
Dan Namarika ◽  
Maria Chikasema ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Amphotericin B ◽  
Phase Ii ◽  
Cryptococcal Meningitis ◽  
Controlled Trial ◽  
High Dose ◽  
Randomized Controlled ◽  
Short Course

scholarly journals Short-Course Induction Treatment with Intrathecal Amphotericin B Lipid Emulsion for HIV Infected Patients with Cryptococcal Meningitis

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Gerardo Alvarez-Uria ◽  
Manoranjan Midde ◽  
Raghavakalyan Pakam ◽  
Pradeep Sukumar Yalla ◽  
Praveen Kumar Naik ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Risk Reduction ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Lipid Emulsion ◽  
Absolute Risk ◽  
White Blood Cells ◽  
Sub Saharan Africa ◽  
Induction Treatment ◽  
Short Course

Cryptococcal meningitis (CM) is a common cause of death among HIV infected patients in developing countries, especially in sub-Saharan Africa. In this observational HIV cohort study in a resource-limited setting in India, we compared the standard two-week intravenous amphotericin B deoxycholate (AmBd) (Regimen I) with one week of intravenous AmBd along with daily therapeutic lumbar punctures and intrathecal AmB lipid emulsion (Regimen II) during the intensive phase of CM treatment. 78 patients received Regimen I and 45 patients received Regimen II. After adjustment for baseline characteristics (gender, age, altered mental status or seizures at presentation, CD4 cell count, white blood cells, cerebrospinal fluid white cells, and haemoglobin), the use of Regimen II was associated with a significant relative risk reduction in mortality (adjusted hazard ratio 0.4, 95% confidence interval, 0.22–0.76) and 26.7% absolute risk reduction (95% confidence interval, 9.9–43.5) at 12 weeks. The use of Regimen II resulted in lower costs of drugs and hospital admission days. Since the study is observational in nature, we should be cautious about our results. However, the good tolerability of intrathecal administration of AmB lipid emulsion and the clinically important mortality reduction observed with the short-course induction treatment warrant further research, ideally through a randomized clinical trial.

scholarly journals Amphotericin B for cryptococcal meningitis in HIV positive patients: Low dose versus high dose

2007 ◽  
Vol 11 (3) ◽  
pp. 112-116 ◽  
Author(s):  
S. Rajeshwari ◽  
Prabha M.R. Adhikari* ◽  
John T. Ramapuram* ◽  
Satish Rao* ◽  
M.R.S.M. Pai ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Low Dose ◽  
Hiv Positive ◽  
High Dose

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 Comparative Effectiveness of Induction Therapy for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: A Network Meta-Analysis

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Jeffrey I. Campbell ◽  
Steve Kanters ◽  
John E. Bennett ◽  
Kristian Thorlund ◽  
Alexander C. Tsai ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amphotericin B ◽  
Induction Therapy ◽  
Cryptococcal Meningitis ◽  
Comparative Effectiveness ◽  
Treatment Guidelines ◽  
Meta Analysis ◽  
High Dose ◽  
Mortality Benefit ◽  
Immunodeficiency Virus

Abstract Background.  Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin-fluconazole. Methods.  We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine +triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results.  In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not ide.jpegy a benefit for combination therapy in restricted analyses in either resource-rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions.  Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virus-associated cryptococcal meningitis.

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