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Revista Chilena de Infectologia :... Dec 2011The echinocandins, caspofugin, micafungin, and anidulafungin, are lipopeptides that inhibit fungal growth by binding to β - (1.3) d glucan synthase. This enzyme is... (Review)
Review
The echinocandins, caspofugin, micafungin, and anidulafungin, are lipopeptides that inhibit fungal growth by binding to β - (1.3) d glucan synthase. This enzyme is responsible for the formation of the peptidoglycan cell wall, and it is essential in fungi such as Candida spp, but less important in the case of Aspergillus and Fusarium species. We review the history, pharmacology and clinical trials that have showed clinical efficacy similar to amphotericin B for the management of fungal infections such as candidemia, invasive candidiasis and aspergillosis, even in cases refractory to initial treatment. These drugs have less toxicity and discontinuation is uncommonly required. Despite similar spectrum and tolerability, there are several pharmacological differences. Only a few clinical trials compare the clinical efficacy between them and their clinical application cannot be generalized. However, the echinocandins have demonstrated clinical efficacy in patients with invasive candidiasis and in others forms of systemic mycoses.
Topics: Anidulafungin; Antifungal Agents; Aspergillus; Candida; Caspofungin; Clinical Trials as Topic; Echinocandins; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests
PubMed: 22286675
DOI: No ID Found -
Clinical Pharmacokinetics Mar 2018Micafungin is a selective inhibitor of the synthesis of fungal 1,3-β-D-glucan, an essential component of the fungal cell wall. It is available as a powder for infusion... (Review)
Review
Micafungin is a selective inhibitor of the synthesis of fungal 1,3-β-D-glucan, an essential component of the fungal cell wall. It is available as a powder for infusion only and is registered for the treatment of invasive and esophageal candidiasis in addition to prophylaxis of Candida infections in both adults and children. Average exposure after a single intravenous 100 mg dose in healthy adults is 133 mg h/L. Both exposure and maximum plasma concentration show linear dose proportional pharmacokinetics (PK) over a 0.15-8 mg/kg dose range. In healthy adults, the clearance (CL) is 10.4 mL/h/kg and volume of distribution is 0.2 L/kg; both are independent of the dose. Micafungin is metabolized by arylsulfatase, catechol-O-methyltransferase, and several cytochrome P450 (CYP) isoenzymes (3A4, 1A2, 2B6 and 2C), but no dose adjustments are necessary in patients with (severe) hepatic dysfunction. Exposure to micafungin is lower in hematology patients, and is even further lowered in critically ill patients (including burn patients) compared with healthy volunteers, which might have consequences for treatment efficacy. In children, an increased CL has been reported: 40-80 mL/h/kg in premature neonates and 20 mL/h/kg in children >4 months of age. Therefore, relatively higher doses of 4-10 mg/kg in premature neonates and 2-4 mg/kg in children with invasive candidiasis are used. However, these higher CLs may also be explained by the eightfold higher free fraction of unbound micafungin in premature neonates, meaning that an augmented dose might not be required.
Topics: Adult; Antifungal Agents; Candidiasis; Candidiasis, Invasive; Child; Critical Illness; Dose-Response Relationship, Drug; Esophagitis; Humans; Infant; Infant, Newborn; Micafungin
PubMed: 28791666
DOI: 10.1007/s40262-017-0578-5 -
Antimicrobial Agents and Chemotherapy Jun 2021Concentrations of anidulafungin and micafungin were determined in eight different tissues obtained during autopsy of four deceased individuals who had been treated with...
Concentrations of anidulafungin and micafungin were determined in eight different tissues obtained during autopsy of four deceased individuals who had been treated with anidulafungin and of seven who had received micafungin. The largest amounts were recovered from liver, with anidulafungin concentrations of 11.01 to 66.50 μg/g and micafungin levels of 0.36 to 5.53 μg/g (0.65 μg/g 30 days after the last administration). The lowest anidulafungin levels were measured in skeletal muscle, and the lowest micafungin concentrations were in kidneys.
Topics: Anidulafungin; Antifungal Agents; Echinocandins; Humans; Lipopeptides; Micafungin; Tissue Distribution
PubMed: 33875434
DOI: 10.1128/AAC.00169-21 -
Medical Mycology Journal 2011
Review
Topics: Antifungal Agents; Candidiasis; Catheters; Contraindications; Cross Infection; Disease Susceptibility; Echinocandins; Fluconazole; Humans; Immunocompromised Host; Immunosuppressive Agents; Lipopeptides; Micafungin; Risk Factors; Transplantation
PubMed: 21441708
DOI: 10.3314/jjmm.52.15 -
Antimicrobial Agents and Chemotherapy Jun 2020Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin...
Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01 to 0.66 μg/ml) and micafungin levels (<0.01 to 0.16 μg/ml) were lower than those in plasma concentrations (0.77 to 5.07 and 1.21 to 8.70 μg/ml, respectively) drawn simultaneously. In cerebral cortex, anidulafungin and micafungin levels were 0.21 to 2.34 and 0.18 to 2.88 μg/g, respectively. Thus, MIC values of several pathogenic strains exceed concentrations in CSF and in brain.
Topics: Adult; Anidulafungin; Antifungal Agents; Cerebral Cortex; Echinocandins; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests
PubMed: 32340985
DOI: 10.1128/AAC.00275-20 -
Viruses Feb 2023Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses...
Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses such as flavivirus, alphavirus, and coronavirus. In this study, we focused on micafungin and its derivatives and analyzed their antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The micafungin derivatives Mi-2 and Mi-5 showed higher antiviral activity than micafungin, with 50% maximal inhibitory concentration (IC) of 5.25 and 6.51 µM, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC) of >64 µM in VeroE6/TMPRSS2 cells. This high anti-SARS-CoV-2 activity was also conserved in human lung epithelial cell-derived Calu-3 cells. Micafungin, Mi-2, and Mi-5 were suggested to inhibit the intracellular virus replication process; additionally, these compounds were active against SARS-CoV-2 variants, including Delta (AY.122, hCoV-19/Japan/TY11-927/2021), Omicron (BA.1.18, hCoV-19/Japan/TY38-873/2021), a variant resistant to remdesivir (R10/E796G C799F), and a variant resistant to casirivimab/imdevimab antibody cocktail (E406W); thus, our results provide basic evidence for the potential use of micafungin derivatives for developing antiviral agents.
Topics: Humans; Antiviral Agents; COVID-19; Micafungin; RNA Replication; RNA, Viral; SARS-CoV-2
PubMed: 36851666
DOI: 10.3390/v15020452 -
The Pediatric Infectious Disease Journal Nov 2014Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants. (Comparative Study)
Comparative Study Review
BACKGROUND
Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants.
METHODS
Safety and efficacy outcomes of micafungin were compared between prematurely and non-prematurely born infants <2 years of age. Data were obtained from all completed phase I-III clinical trials with micafungin that had enrolled infants (<2 years of age) that were listed in the Astellas Clinical Study Database. Demographics, adverse events, hepatic function tests and treatment success data were extracted and validated by the Astellas biostatistical group for all micafungin-treated patients, <2 years of age, using the unique patient identifier.
RESULTS
One-hundred and sixteen patients included in 9 clinical trials, 48% premature [birth weight (BW) <2500 g and/or gestational age <37 weeks], 52% non-premature, received ≥ 1 dose of micafungin. Among premature patients, 14.5% were low BW (1500-2499 g), 36.4% very low BW (1000-1499 g) and 49.1% extremely low BW (<1000 g). Ninety patients (78%) completed the studies; 13 [11% (4 premature)] died. Significantly more non-premature than premature patients discontinued treatment (P = 0.003). Treatment-related adverse events were recorded in 23% of patients with no difference between groups. More extremely low BW (n = 4, 15%) and very low BW (n = 8, 40%) infants experienced treatment-related adverse events than low BW (n = 0) and there was no relation to micafungin dose or duration. For a subgroup of 30 patients with invasive candidiasis, treatment success was achieved in 73% in both premature and non-premature groups. Prophylaxis was successful in 4/5 non-premature hematopoietic stem cell transplant patients.
CONCLUSION
Micafungin has a safe profile in premature and non-premature infants with substantial efficacy.
Topics: Antifungal Agents; Clinical Trials as Topic; Echinocandins; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Micafungin; Mycoses; Term Birth
PubMed: 24892849
DOI: 10.1097/INF.0000000000000434 -
Cellular Physiology and Biochemistry :... 2016The antifungal drug Micafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. Side effects of Micafungin treatment...
BACKGROUND/AIMS
The antifungal drug Micafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. Side effects of Micafungin treatment include microangiopathic hemolytic anemia and thrombocytopenia with microvascular thrombosis. The development of thrombosis may be fostered by stimulation of eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, activated protein kinase C (PKC), casein kinase 1α or p38 kinase and activated caspases. The present study explored, whether Micafungin induces eryptosis.
METHODS
Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Hemolysis was quantified by measuring haemoglobin concentration in the supernatant.
RESULTS
A 48 hours exposure of human erythrocytes to Micafungin (10 - 25 µg/ml) significantly increased hemolysis and the percentage of annexin-V-binding cells, and significantly decreased forward scatter. Micafungin (25 µg/ml) did not significantly modify Fluo3-fluorescence, DCFDA fluorescence, or ceramide abundance. The effect of Micafungin on annexin-V-binding was not significantly modified by removal of extracellular Ca2+, by PKC inhibitor staurosporine (1 µM), p38 kinase inhibitor SB203580 (2 µM), casein kinase 1α inhibitor D4476 (10 µM) or pancaspase inhibitor zVAD (10 µM).
CONCLUSIONS
Micafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane.
Topics: Antifungal Agents; Benzamides; Calcium; Casein Kinase I; Cell Size; Ceramides; Echinocandins; Eryptosis; Erythrocyte Membrane; Erythrocytes; Flow Cytometry; Hemolysis; Humans; Imidazoles; Lipopeptides; Micafungin; Microscopy, Confocal; Phosphatidylserines; Protein Kinase C; Pyridines; Reactive Oxygen Species; Staurosporine; p38 Mitogen-Activated Protein Kinases
PubMed: 27394133
DOI: 10.1159/000445650 -
European Journal of Medical Research Apr 2011Working by a distinct cell wall-specific mechanism of action, the echinocandin class of antifungals has substantially expanded the range of available treatments for... (Review)
Review
Working by a distinct cell wall-specific mechanism of action, the echinocandin class of antifungals has substantially expanded the range of available treatments for invasive Candida infections. Anidulafungin, caspofungin and micafungin were investigated versus drugs from earlier antifungal classes in large clinical trials that demonstrated their excellent clinical and microbiological efficacy in the primary treatment of invasive candidiasis. Therefore, and supported by a number of favourable pharmacological characteristics, the echinocandins rapidly became established in guidelines and clinical practice as primary treatment options for moderately to severely ill patients with invasive candidiasis. This article reviews the relevant clinical evidence that forms the basis for the use of echinocandins in the management of invasive candidiasis, and discusses their current role in the context of recent guideline recommendations and treatment optimization strategies.
Topics: Anidulafungin; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Clinical Trials as Topic; Drug Interactions; Echinocandins; Guidelines as Topic; Humans; Lipopeptides; Micafungin
PubMed: 21486731
DOI: 10.1186/2047-783x-16-4-167