A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations

Barrett, Jane; Vardulaki, Katerina; Conlon, Christopher P.; Cooke, Jonathan; Daza-Ramirez, Pascual; Evans, E. G. V.; Hawkey, Peter M.; Herbrecht, Raoul; Marks, David I.; Moraleda, José M.; Park, Gilbert R.; Senn, Stephen; Viscoli, Claudio

doi:10.1016/s0149-2918(03)80125-x

Cited by 162 publications

(75 citation statements)

References 30 publications

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“…Since then, amphotericin B has been used in the clinic and is still regarded as a golden standard and a life-saving drug in the treatment of many severe fungal infections (1)(2)(3). However, the medical application of AmB is limited by its toxicity and poor solubility, necessitating hospitalization and parenteral administration (1).…”

Section: Introductionmentioning

confidence: 99%

Development of Amphotericin B-Loaded Cubosomes Through the SolEmuls Technology for Enhancing the Oral Bioavailability

et al. 2012

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Abstract. The oral administration of amphotericin B (AmB) has the major drawback of poor bioavailability. The aim of this work was to evaluate the potential of AmB-loaded cubosomes as an oral formulation with improved bioavailability. This manuscript firstly developed AmB-loaded cubosomes by using the SolEmuls technology. The encapsulation efficiency, the in vitro release, and stability studies in simulated gastrointestinal fluid were used to evaluate AmB-loaded cubosomes. The acute nephrotoxicity, bioavailability, and tissue distribution study of AmB-loaded cubosomes were assayed upon oral administration to rats. SAXS and cryo-TEM exhibited AmB-loaded cubosomes as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. The encapsulation efficiency and the results of in vitro release and stability studies in simulated gastrointestinal fluid further demonstrated that AmB was successfully encapsulated in cubosomes. AmB-loaded cubosomal formulation orally administrated in rats did not show nephrotoxicity and its relative bioavailability was approximately 285% as compared to Fungizone®. The AmB-loaded cubosomal formulation presented an effective potential approach for enhancing the oral bioavailability of AmB.

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Section: Introductionmentioning

confidence: 99%

Development of Amphotericin B-Loaded Cubosomes Through the SolEmuls Technology for Enhancing the Oral Bioavailability

et al. 2012

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“…The prognosis in neutropenic patients is especially poor, with a fatality rate of 56% to 100% (16,23,24,29,31). To date, the antifungal of choice has been amphotericin B at the highest tolerable doses (3,12,36). Because morbidity and mortality remain high, especially in immunocompromised patients, new and better treatments are needed to reduce death and disfigurements.…”

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confidence: 99%

Posaconazole as Salvage Therapy for Zygomycosis

Greenberg

Mullane

Burik

et al. 2006

Antimicrob Agents Chemother

509

307

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Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.Zygomycosis (also known as mucormycosis) is an infection caused by saprophytic fungi of the class Zygomycetes, which are primarily opportunists that invade immunocompromised hosts and produce angioinvasive disease (49). Transmission is mainly through inhalation of small airborne spores, by traumatic skin implantation, or by ingestion and translocation of the organism through the gut. Patients at highest risk for zygomycosis are those with (i) immunosuppression related to neutropenia, corticosteroid use, hematologic malignancies, and solid-organ transplants, (ii) diabetes mellitus, especially those with ketoacidosis, (iii) conditions of iron overload with associated desferoxamine use, and (iv) skin disruption by trauma or other serious conditions, such as burns or heatstroke. In recipients of a hematopoietic stem cell transplant (HSCT), infection often occurs during periods of graft-versus-host disease due to escalation of immunosuppressant regimens (1,4,12,21,25,27,36,41,44). Common sites of infection include pulmonary, rhinocerebral, or disseminated disease (36). The outcome of zygomycosis is closely related to the overall health of the patients and the control of their underlying diseases.Roden and associates analyzed 929 cases of zygomycosis reported since 1885 (38). Survival was reported in 65% of patients with no underlying condition, 56% with diabetes, and 34% with malignancy. Survival varied with infection site: localized skin, 90%; rhinocerebral, 38%; lung, 24...

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“…The NNT value of eight indicates that if eight patients are treated with voriconazole instead of CAB, one additional death will be averted within a 12-week timeframe. For comparison, a recent meta-analysis of the antifungal effectiveness and tolerability of amphotericin B formulations in the treatment of systemic fungal infections estimated that, overall, 31 patients need to be treated with lipid formulations of amphotericin B instead of CAB in order to prevent one death (10).…”

Section: Discussionmentioning

confidence: 99%

“…Although a meta-analysis of all lipid formulations in comparison with CAB for systemic fungal infections demonstrated a significantly reduced risk of all-cause mortality, no significant difference in treatment success rate between the lipid formulations and CAB was found (10). Itraconazole, an azole antifungal agent, has similar efficacy as CAB when administered orally (11), and guidelines recommend oral itraconazole as follow-up therapy after initial treatment with CAB (6).…”

mentioning

confidence: 99%

An Economic Evaluation of Voriconazole versus Amphotericin B for the Treatment of Invasive Aspergillosis in Canada

Rotstein

Laverdière

Marciniak

et al. 2004

Canadian Journal of Infectious Diseases and Medical Microbiolog

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BACKGROUND: Invasive aspergillosis (IA) is a serious fungal infection that affects immunocompromised patients. The Global Comparative Aspergillosis study demonstrated that voriconazole, a new broad-spectrum triazole, had better responses and improved survival compared with conventional amphotericin B deoxycholate (CAB) and other licensed antifungal therapy (OLAT) for the treatment of definite or probable aspergillosis.OBJECTIVES: To compare costs and outcomes of voriconazole and CAB for the treatment of definite or probable aspergillosis in Canada.METHODS: A cost-consequence decision tree model was designed to reflect the treatment pathways used in clinical practice when using voriconazole or CAB as primary therapy for IA. Therapy included initial treatment with either voriconazole or CAB and then switched to an OLAT in the event of an inadequate response, severe toxicity or intolerance. The principal data source used was the Global Comparative Aspergillosis study.RESULTS: The total cost of voriconazole when compared with CAB as initial therapy for IA was $38,319 versus $42,495 per patient, respectively, representing a 9.8% cost reduction for each patient treated with voriconazole. The higher mean cost in the CAB arm was primarily due to the high proportion of patients (73.7%) who were switched to an OLAT due to severe side effects or an inadequate response. Treating with voriconazole was a dominant strategy. The number of patients that had to be treated with voriconazole instead of CAB to save one additional life was eight.CONCLUSIONS: Voriconazole as primary treatment for IA increased the chances of successful treatment, improved survival and may represent a potential cost saving strategy in Canada.

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A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations

Cited by 162 publications

References 30 publications

Development of Amphotericin B-Loaded Cubosomes Through the SolEmuls Technology for Enhancing the Oral Bioavailability

Development of Amphotericin B-Loaded Cubosomes Through the SolEmuls Technology for Enhancing the Oral Bioavailability

Posaconazole as Salvage Therapy for Zygomycosis

An Economic Evaluation of Voriconazole versus Amphotericin B for the Treatment of Invasive Aspergillosis in Canada

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