Amphotericin B in the Era of New Antifungals: Where Will It Stand?
Abstract
:1. Introduction
2. Amphotericin B Past and Present
2.1. Mechanism of Action
2.2. Pharmacokinetic Parameters
2.3. Safety and Interactions
2.4. Liposomal Amphotericin B Efficacy and Place in Current Recommendations
3. Unmet Needs in the Diagnosis and Management of Fungal Infections
3.1. Early Diagnosis
3.2. Regimen Spectra and Properties
3.3. Increasing Resistance, Emergent Pathogens, and Breakthrough Infections
3.4. Respiratory Patient Populations
3.5. Critically Ill Patients
4. New Antifungals in the Era of Unmet Needs
4.1. Rezafungin
4.2. Fosmanogepix
4.3. Olorofilm
4.4. Ibrexafungerp
4.5. Oteseconazole
4.6. Encochleated Amphotericin B
5. Amphotericin B Future Perspectives
AmphotericinB | Rezafungin | Fosmanogepix | Olorofim | Ibrexafungerp | Oteseconazole | |
---|---|---|---|---|---|---|
Candida albicans | ||||||
Candida glabrata | ||||||
Candida parapsilosis | ||||||
Candida tropicalis | ||||||
Candida krusei | ||||||
Candida lusitaniae | ||||||
Aspergillus fumigatus | ||||||
Cryptococcus neoformans | ||||||
Mucorales | ||||||
Fusarium spp. | ||||||
Scedosporium spp. | ||||||
Blastomyces dermatitidis | ||||||
Coccidioides immitis | ||||||
Histoplasma capsulatum | ||||||
No data | Moderate activity | |||||
No/Minor activity | Strong activity |
5.1. Spectrum and Timely Initiation
5.2. Increasing Resistance, Emergent Pathogens, and Breakthrough Infections
5.3. Respiratory Patient Populations
5.4. Critically Ill Patients
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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Recommending Body | Invasive Mycoses | L-AmB |
---|---|---|
Adult Patients | ||
ESCMID/ECMM/ERS, 2017 [51] | Empiric therapy | B I |
Invasive pulmonary aspergillosis | B II | |
Refractory invasive aspergillosis | B II | |
ESCMID, 2012 [52] | Candidemia and invasive candidiasis | B I |
ECMM, 2019 [50] | Mucormycosis | A II |
Mucormycosis with CNS involvement | A III | |
ECIL-6, 2017 [53] | Invasive aspergillosis | B I |
Candidemia (overall population) | A I | |
Mucormycosis | B II | |
IDSA, 2016 [54,55] | Candidemia in non-neutropenic patients as an alternative therapy | Strong recommendation, high quality of evidence |
Candidemia in neutropenic patients as an alternative therapy | Strong recommendation, moderate quality of evidence | |
Invasive aspergillosis as an alternative therapy | Strong recommendation, moderate quality of evidence | |
Paediatric Patients | ||
ESCMID/ECMM, 2019 [56] | Invasive aspergillosis | B II |
ESCMID, 2012 [57] | Invasive candidiasis in infants | B II |
ESCMID/ECMM, 2014 [50] | Mucormycosis | A II |
ECIL-8, 2020 [58] | Empiric therapy | A I |
Invasive aspergillosis | B II | |
Invasive candidiasis | A II | |
Mucormycosis | A II |
AmB | 5FC | FLU | ITR | VOR | POS | ISA | CAS | MICA | ANI | |
---|---|---|---|---|---|---|---|---|---|---|
Candida albicans | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ |
Candida glabrata | ++ | ++ | + | + | ++ | ++ | ++ | + | + | + |
Candida parapsilosis | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ |
Candida tropicalis | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ |
Candida krusei | ++ | + | - | + | ++ | ++ | ++ | ++ | ++ | ++ |
Candida lusitaniae | - | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ | ++ |
Aspergillus fumigatus | ++ | - | - | + | ++ | ++ | ++ | + | + | + |
Cryptococcus neoformans | ++ | ++ | ++ | ++ | ++ | ++ | ++ | - | - | - |
Mucorales | ++ | - | - | - | - | ++ | ++ | - | - | - |
Fusarium spp. | + | - | - | + | ++ | ++ | ++ | - | - | - |
Scedosporium spp. | + | - | - | + | + | + | + | - | - | - |
Blastomyces dermatitidis | ++ | - | + | ++ | ++ | ++ | ++ | - | - | - |
Coccidioides immitis | ++ | - | ++ | ++ | ++ | ++ | ++ | - | - | - |
Histoplasma capsulatum | ++ | - | + | ++ | ++ | ++ | ++ | - | - | - |
Mechanism of Action | Route of Administration | Spectrum (See Table 4) | Adverse Effects | |
---|---|---|---|---|
Amphotericin B | Binds to ergosterol, disrupting fungal cell membrane integrity | IV | Broad spectrum, including Aspergillus, Candida, and other molds | Nephrotoxicity, infusion-related reactions, electrolyte imbalances |
Rezafungin | Inhibits fungal protein synthesis | IV | Broad spectrum, including Candida and Aspergillus | Gastrointestinal disturbances, hepatotoxicity, QT prolongation |
Fosmanogepix | Inhibits glucan synthesis, disrupting fungal cell wall | IV | Broad spectrum, including Candida and Aspergillus | Gastrointestinal disturbances, increased liver enzymes, QT prolongation |
Olorofim | Inhibits fungal ergosterol synthesis | Oral and IV | Broad spectrum, including Aspergillus and some molds | Gastrointestinal disturbances, hepatotoxicity, QT prolongation |
Ibrexafungerp (formerly SCY-078) | Inhibits fungal beta-glucan synthesis | Oral and IV | Broad spectrum, including Candida and some molds | Gastrointestinal disturbances, hepatotoxicity, QT prolongation |
Oteseconazole | Inhibits fungal ergosterol synthesis | Oral | Broad spectrum, including Candida and Aspergillus | Gastrointestinal disturbances, hepatotoxicity, QT prolongation |
Encochleated Amphotericin B | Binds to ergosterol, disrupting fungal cell membrane integrity | IV | Broad spectrum, including Aspergillus, Candida, and other molds | Nephrotoxicity, infusion-related reactions, electrolyte imbalances |
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Akinosoglou, K.; Rigopoulos, E.A.; Papageorgiou, D.; Schinas, G.; Polyzou, E.; Dimopoulou, E.; Gogos, C.; Dimopoulos, G. Amphotericin B in the Era of New Antifungals: Where Will It Stand? J. Fungi 2024, 10, 278. https://doi.org/10.3390/jof10040278
Akinosoglou K, Rigopoulos EA, Papageorgiou D, Schinas G, Polyzou E, Dimopoulou E, Gogos C, Dimopoulos G. Amphotericin B in the Era of New Antifungals: Where Will It Stand? Journal of Fungi. 2024; 10(4):278. https://doi.org/10.3390/jof10040278
Chicago/Turabian StyleAkinosoglou, Karolina, Emmanouil Angelos Rigopoulos, Despoina Papageorgiou, Georgios Schinas, Eleni Polyzou, Effrosyni Dimopoulou, Charalambos Gogos, and George Dimopoulos. 2024. "Amphotericin B in the Era of New Antifungals: Where Will It Stand?" Journal of Fungi 10, no. 4: 278. https://doi.org/10.3390/jof10040278