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

Bicanic, Tihana; Bottomley, Christian; Loyse, Angela; Brouwer, Annemarie E.; Muzoora, Conrad; Taseera, Kabanda; Jackson, Arthur; Phulusa, Jacob; Hosseinipour, Mina C.; Horst, Charles van der; Limmathurotsakul, Direk; White, Nicholas J.; Wilson, Douglas P.; Wood, Robin; Meintjes, Graeme; Harrison, Thomas S.; Jarvis, Joseph N

doi:10.1128/aac.01698-15

Cited by 106 publications

(109 citation statements)

References 41 publications

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“…Despite its long history of use as one of the most potent antifungals, acquired resistance to amphotericin B is not common . Nevertheless, the conventional formulation (amphotericin B deoxycholate [d‐AmB]) is associated with several adverse events, including infusion‐related toxicity (eg chills, fever, nausea and vomiting) as well as nephrotoxicity, which can result in death …”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of amphotericin B lipid‐based formulations—A systematic review and meta‐analysis

Steimbach

Tonin

Virtuoso

et al. 2016

Mycoses

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Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta-analyses were performed. Twenty-three RCTs were identified (n=2677 participants) for meta-analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta-analysis showed that conventional amphotericin B presents the same efficacy profile as lipid-based formulations, although the latter were associated with a safer profile.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of amphotericin B lipid‐based formulations—A systematic review and meta‐analysis

Steimbach

Tonin

Virtuoso

et al. 2016

Mycoses

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“…7 However, these drugs have severe side Nevertheless, in rare cases, this chronic granulomatous process can lead to formation of a mass (cryptococcoma) that has a tumoral appearance. 9 Metabolites released by Cryptococcus can inhibit the migration and function of leukocytes and promote survival and localized replication of the pathogen, thus facilitating chronic granulomatous inflammation and cryptococcoma formation.…”

Section: Case Reportmentioning

confidence: 99%

Cryptococcoma mimicking a brain tumor in an immunocompetent patient: case report of an extremely rare presentation

et al. 2017

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CONTEXT: Central nervous system (CNS) infectious diseases have high prevalence in developing countries and their proper diagnosis and treatment are very important for public health planning. Cryptococcus neoformans is a fungus that may cause several CNS manifestations, especially in immunocompromised patients. Cryptococcal meningitis is the most common type of involvement. Mass-effect lesions are uncommon: they are described as cryptococcomas and their prevalence is even lower among immunocompetent patients. The aim here was to report an extremely rare case of cryptococcoma causing a mass effect and mimicking a brain tumor in an immunocompetent patient. The literature on CNS cryptococcal infections was reviewed with emphasis on cryptococcomas. Clinical, surgical and radiological data on a female patient with this rare presentation of cryptococcoma mimicking a brain tumor are described. CASE REPORT: A 54-year-old female patient presented to the emergency department with a rapid-onset progressive history of confusion and completely dependency for basic activities. Neuroimaging showed a left occipital lesion and neurosurgical treatment was proposed. From histopathological evaluation, a diagnosis of cryptococcoma was established. She received clinical support with antifungals, but despite optimal clinical treatment, her condition evolved to death. CONCLUSIONS: Cryptococcal infections have several forms of presentation and, in immunocompetent patients, their manifestation may be even more different. Cryptococcoma is an extremely rare presentation in which proper surgical and clinical treatment should be instituted as quickly as possible, but even so, there is a high mortality rate.

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“…Amphotericin B requires intravenous administration and close laboratory monitoring and is associated with phlebitis, secondary infections, anemia, and renal impairment. 6 Flucytosine is currently unavailable, although the molecule is used widely as a constituent of emtricitabine, and generic manufacture is possible at low cost. 7 Most countries therefore rely on generic or donated fluconazole induction monotherapy; however, the rate of fungal clearance with fluconazole is slower than that with amphotericin B, even at an elevated dosage, and mortality associated with this treatment is 50 to 60% at 10 weeks and is higher than 70% at 1 year even in study cohorts.…”

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confidence: 99%

Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa

et al. 2018

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BACKGROUNDCryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODSWe randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTSA total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P = 0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen.

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

Cited by 106 publications

References 41 publications

Efficacy and safety of amphotericin B lipid‐based formulations—A systematic review and meta‐analysis

Efficacy and safety of amphotericin B lipid‐based formulations—A systematic review and meta‐analysis

Cryptococcoma mimicking a brain tumor in an immunocompetent patient: case report of an extremely rare presentation

Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa

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