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Critical Reviews in Analytical Chemistry 2021Micafungin is characterized as one of the most active available drugs for candidemia treatment; however, their use is also associated in prophylaxis protocols in cases... (Review)
Review
Micafungin is characterized as one of the most active available drugs for candidemia treatment; however, their use is also associated in prophylaxis protocols in cases of invasive fungal infections. The use of this drug is widely appreciated in the medical field due to be the most active echinocandin available for invasive fungal infections. In order to provide important parameters related to the chemical, physical, biological and therapeutic characteristics, this review article gathers important research results that demonstrate the biological potential of this drug, as well as to present analytical methods that can be used to determine the antifungal potential and a monitoring of administered dosages. Important studies about the methods most commonly used in biological activity evaluation and determination/quantification by analytical methods are provided in this review article. With the data provided, the scientific community will have the possibility to choose the analytical methods and biological that can be employed in clinical and scientific research to provide greater safety and reliability of the results to be found.
Topics: Antifungal Agents; Aspergillus fumigatus; Candida; Candidiasis; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Echinocandins; Electrophoresis, Capillary; Humans; Micafungin; Solubility; Tandem Mass Spectrometry; Treatment Outcome
PubMed: 32064916
DOI: 10.1080/10408347.2020.1726726 -
The Journal of Pharmacy and Pharmacology Jan 2022Echinocandins are widely used for the treatment of invasive fungal diseases. While they bind strongly to plasma proteins, our knowledge of this process is not sufficient... (Comparative Study)
Comparative Study
OBJECTIVES
Echinocandins are widely used for the treatment of invasive fungal diseases. While they bind strongly to plasma proteins, our knowledge of this process is not sufficient to permit their pharmacokinetics and pharmacodynamics targets to be discussed. In this study, we characterized the binding of two echinocandins, caspofungin and micafungin, to plasma proteins, human serum albumin (HSA) and human α 1-acid glycoprotein (AAG).
METHODS
The binding parameters, number of binding sites (n) and association constant (K) for caspofungin and micafungin to HSA and AAG were determined by equilibrium dialysis. The binding site on HSA for these echinocandins was identified by conducting inhibition experiments.
KEY FINDINGS
Caspofungin was found to bind strongly to a single site on HSA (n = 1.26, K = 0.45 × 106 M-1) and AAG (n = 0.99, K = 0.29 × 106 M-1). Micafungin was found to bind more strongly to HSA (n = 1.35, K = 1.44 × 106 M-1) and AAG (n = 1.32, K = 1.16 × 106 M-1). The binding site for these drugs on HSA appears to be within subdomain IA.
CONCLUSIONS
Free fraction of caspofungin and micafungin in patients may not be substantially affected due to the contribution of AAG to the overall protein binding and the binding to subdomain IA on HSA, which is different from the major drug-binding sites within subdomains IB, IIA and IIIA.
Topics: Antifungal Agents; Binding Sites; Blood Proteins; Caspofungin; Echinocandins; Humans; In Vitro Techniques; Invasive Fungal Infections; Micafungin; Microbial Sensitivity Tests; Orosomucoid; Protein Binding; Serum Albumin, Human
PubMed: 34791369
DOI: 10.1093/jpp/rgab157 -
Antimicrobial Agents and Chemotherapy Mar 2021Limited data are available on the most appropriate dosing, efficacy, and safety of micafungin in neonates and young infants with invasive candidiasis (IC). This study...
Limited data are available on the most appropriate dosing, efficacy, and safety of micafungin in neonates and young infants with invasive candidiasis (IC). This study evaluated plasma levels, efficacy, and safety of micafungin at a dose of 8 mg/kg daily for a mean of 13.3 days (±5.2 days) in 35 neonates and young infants with IC. Micafungin plasma concentrations were 5.70 mg/liter preadministration and 17.23, 15.59, and 10.27 mg/liter after 1, 2, and 8 h, respectively. The resolution of the infection was achieved in 86.7% of patients treated for ≥14 days. In 20.0% of patients, we observed a transient hypertransaminasemia. Micafungin at a dose of 8 mg/kg daily is effective and well tolerated in neonates and young infants with IC. (This study has been registered at ClinicalTrials.gov under identifier NCT03421002 and in the EU Clinical Trials Register under number 2014-003087-20.).
Topics: Antifungal Agents; Candidiasis, Invasive; Echinocandins; Humans; Infant; Infant, Newborn; Lipopeptides; Micafungin
PubMed: 33558294
DOI: 10.1128/AAC.02494-20 -
Mycoses Nov 2022Rezafungin, a new echinocandin with an extended half-life, exhibits potent activity against Candida spp. Aside from the MIC, specific interactions between antifungal and...
Rezafungin, a new echinocandin with an extended half-life, exhibits potent activity against Candida spp. Aside from the MIC, specific interactions between antifungal and isolate, including the duration of anti-infective activity, may impact dose interval choices and infection outcome. We evaluated rezafungin and micafungin post-antifungal effect (PAFE) against C. albicans, C. parapsilosis and C. glabrata. Six Candida spp. isolates were tested, including two of each species, C. albicans, C. parapsilosis and C. glabrata. Antifungal susceptibility testing was performed using the CLSI reference broth microdilution method. Antifungal concentrations of 1x, 4x and 16x the baseline MIC were used for PAFE determinations. Colony counts were performed at T0 (pre-exposure), after the 1-h drug exposure, after the cell wash (T1), and at T2, T4, T8, T12, T24 and T48 h. Rezafungin PAFE results were equivalent to micafungin PAFE values for one C. albicans (>14.9 h) and both C. glabrata (>40 h) isolates for all concentrations tested. The rezafungin and micafungin PAFEs could not be determined against one C. albicans isolate. Prolonged PAFE results were also noted for rezafungin (range, 18.4 to >40 h) against both C. parapsilosis isolates at all concentrations, while no micafungin PAFE or a short PAFE (range, 1.8 to 7.4 h) was observed against these organisms, except at 16x bMIC. Rezafungin showed sustained growth inhibition following drug removal and displayed equivalent or longer PAFE values than micafungin against all tested Candida spp.
Topics: Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Echinocandins; Humans; Micafungin; Microbial Sensitivity Tests
PubMed: 35778886
DOI: 10.1111/myc.13490 -
Medizinische Klinik, Intensivmedizin... Sep 2023Invasive fungal infections caused by Candida or Aspergillus are associated with a high mortality. Knowledge about the risk factors, diagnosis and treatment management... (Review)
Review
BACKGROUND
Invasive fungal infections caused by Candida or Aspergillus are associated with a high mortality. Knowledge about the risk factors, diagnosis and treatment management is crucial for improving the survival of those affected.
OBJECTIVE
To give a practical overview about risk factors and treatment management of Candida and Aspergillus infections as well as providing an outlook on new antifungal agents.
MATERIAL AND METHODS
Summary of the relevant literature and recommendations on candidemia and invasive candidiasis as well as invasive and chronic pulmonary aspergillosis.
RESULTS
The first line treatment of candidemia and invasive candidiasis are echinocandins including caspofungin, anidulafungin and micafungin. Regular blood cultures have to be taken to determine the duration of treatment. After the first negative control blood culture treatment should be continued for another 14 days. The first line treatment of invasive pulmonary aspergillosis is azoles including voriconazole and isavuconazole. The duration of treatment depends on disease severity and is recommended for 6-12 weeks. The duration of treatment for chronic pulmonary aspergillosis is 6-12 months. Therapeutic drug monitoring is recommended for voriconazole and for posaconazole. New antifungal agents including olorofim, fosmanogepix, opelconazole, rezafungin or ibrexafungerp will broaden the therapeutic spectrum in the foreseeable future.
CONCLUSION
Knowledge about risk factors and the correct treatment management is crucial for the survival of patients with invasive fungal infections.
Topics: Humans; Antifungal Agents; Candida; Voriconazole; Candidemia; Aspergillus; Invasive Fungal Infections; Pulmonary Aspergillosis; Candidiasis, Invasive
PubMed: 37644243
DOI: 10.1007/s00063-023-01051-6 -
Microbial Biotechnology Jan 2024Invasive fungal infections have increased remarkably, which have become unprecedented concern to human health. However, the effectiveness of current antifungal drugs is... (Review)
Review
Invasive fungal infections have increased remarkably, which have become unprecedented concern to human health. However, the effectiveness of current antifungal drugs is limited due to drug resistance and toxic side-effects. It is urgently required to establish the effective biosynthetic strategy for developing novel and safe antifungal molecules economically. Echinocandins become a promising option as a mainstay family of antifungals, due to specifically targeting the fungal specific cell wall. To date, three kinds of echinocandins for caspofungin, anidulafungin, and micafungin, which derived from pneumocandin B , echinocandin B, and FR901379, are commercially available in clinic and have shown potential in managing invasive fungal infections in a cost-effective manner. However, current echinocandins-derived precursors all are produced by environmental fungal isolates with long fermentation cycle and low yields, which challenge the production efficacy of these precursors in industry. Therefore, understanding their biosynthetic machinery is of great importance for improving antifungal titres and creating new echinocandins-derived products. With the development of genome-wide sequencing and establishment of gene-editing technology, there are a growing number of reports on echinocandins-derived products and their biosynthetic gene clusters. This review briefly summarizes the discovery and development history of echinocandins, compares their structural characteristics and biosynthetic processes, and sums up existed strategies for improving their production. Moreover, the genomic analysis of related biosynthetic gene clusters of echinocandins is discussed, highlighting the similarities and differences among the clusters. Last, the biosynthetic processes of echinocandins are compared, focusing on the activation and attachment of side-chains and the formation of the hexapeptide core. This review aims to provide insights into the development and production of new echinocandin drugs by modifying the structure of echinocandin-derived precursors and/or optimizing the fermentation processes; and achieve a new microbial chassis for efficient production of echinocandins in heterologous hosts.
Topics: Humans; Antifungal Agents; Echinocandins; Fermentation; Invasive Fungal Infections; Microbial Sensitivity Tests; Lipopeptides
PubMed: 37885073
DOI: 10.1111/1751-7915.14359 -
Mycopathologia Jun 2023Aspergillus species are important causes of invasive fungal disease, particularly among those with an impaired immune system. Increasing reports have revealed a rising...
BACKGROUND
Aspergillus species are important causes of invasive fungal disease, particularly among those with an impaired immune system. Increasing reports have revealed a rising incidence of antifungal drug resistance among Aspergillus spp., particularly among cryptic species. Understanding local antifungal susceptibility patterns is paramount to delivering optimal clinical care.
METHODS
Aspergillus spp. recovered from clinical specimens between 2000 and 2021 from Pathology Queensland were collected. Aspergillus spp. were identified routinely morphologically, and where there was ambiguity or a lack of sporulation, by sequencing of the internal transcribed spacer (ITS) region. All Aspergillus spp. that underwent antifungal susceptibility testing according to the CLSI M38-A3 method and were recorded and included in the study. Amphotericin B, voriconazole, posaconazole, isavuconazole, micafungin, caspofungin, and anidulafungin were tested. Pathology Queensland services all public healthcare facilities in Queensland, Australia.
RESULTS
236 Aspergillus spp. were identified from clinical specimens during the study period. The most frequent species identified were Aspergillus section Fumigati (n = 119), Aspergillus section Flavi (n = 35), Aspergillus terreus (n = 32) and Aspergillus niger (n = 29). Overall, MIC values for voriconazole, posaconazole, itraconazole, and isavuconazole were 0.25/1, 0.25/0.5, 0.25/0.5, and 0.5/2 mg/L respectively. Echinocandins demonstrated low MIC values overall with micafungin and anidulafungin both having an MIC of 0.015/0.03 mg/L. A total of 15 cryptic species were identified; high triazole MIC values were observed with a voriconazole MIC of 2/8 mg/L. From 2017 to 2021 we observed an increase in incidence of isolates with high voriconazole MIC values. There was no difference in voriconazole MIC values between Aspergillus spp. acquired in North Queensland when compared to Southeast Queensland, Australia.
CONCLUSION
Increasing reports of antifungal resistance among Aspergillus spp. is concerning and warrants further investigation both locally and worldwide. Active surveillance of both the emergence of different Aspergillus spp. and changes in antifungal susceptibility patterns over time is crucial to informing clinicians and treatment guidelines.
Topics: Humans; Antifungal Agents; Voriconazole; Anidulafungin; Micafungin; Queensland; Aspergillus; Mycoses; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 37067664
DOI: 10.1007/s11046-023-00713-5 -
Mycopathologia Aug 2020Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. However, there are few studies comparing anidulafungin and micafungin in terms of...
BACKGROUND
Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. However, there are few studies comparing anidulafungin and micafungin in terms of efficacy and safety. The objective of this study was to evaluate the clinical efficacy and safety between anidulafungin and micafungin treatment for adult patients with candidemia.
METHODS
This retrospective cohort study performed on adult candidemia patients diagnosed from January 2006 through December 2018 at a tertiary medical center. The study subjects included adult patients ≥ 19 years with candidemia who were only treated with anidulafungin or micafungin for ≥ 3 days. Clinical characteristics were collected and analyzed. Hepatotoxicity was assessed according to the Common Terminology Criteria for Adverse Events Version 5.0.
RESULTS
A total of 98 patients with candidemia were treated with anidulafungin (n = 52, 53.1%) or micafungin (n = 46, 46.9%). There were no significant differences in age, sex, source of candidemia, and comorbidities between the anidulafungin and micafungin groups. Although there were more patients with abnormal baseline liver function test (LFT) in the anidulafungin group, the rate of clinical response (51.9% vs. 46.7%), mycological response (76.9% vs. 67.4%), and mortality (30-day mortality 26.9% vs. 21.7% and 90-day mortality 78.8% vs. 73.9%) was similar between the anidulafungin and micafungin groups. Also, there was no significant difference in terms of hepatotoxicity, even among the patients with abnormal baseline LFT between the two groups.
CONCLUSIONS
Our results suggest that clinical efficacy and safety may be similar between anidulafungin and micafungin treatment for adult patients with candidemia.
Topics: Aged; Anidulafungin; Antifungal Agents; Candidemia; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Retrospective Studies
PubMed: 32705415
DOI: 10.1007/s11046-020-00471-8 -
Journal of Infection in Developing... Jun 2021An echinocandin, such as micafungin, is recommended as first-line treatment for invasive Candida infections in immunocompromised patients. This multicenter,... (Observational Study)
Observational Study
INTRODUCTION
An echinocandin, such as micafungin, is recommended as first-line treatment for invasive Candida infections in immunocompromised patients. This multicenter, observational, prospective, non- interventional study evaluated the real-world use of micafungin in clinical practice in Slovenia and Romania, as this remains unexplored.
METHODOLOGY
The primary endpoint was evaluation of micafungin use, including rationale for prescription, treatment duration, and daily dose. Secondary endpoints included recordings of patient baseline characteristics and evaluations of efficacy and safety. Across 11 centers in two countries, 118 patients (18 children [< 16 years] and 100 adults [≥ 16 years]) received micafungin for the first time according to their clinic's standard practice.
RESULTS
Micafungin was prescribed for treatment in 57.6% of patients and for prophylaxis in 40.7% of patients. The median (range) treatment duration was 9.0 (0 - 54) days and 13.0 (2 - 6)] days, respectively. The median dose of micafungin was higher than recommended for children receiving prophylaxis or treatment for invasive candidiasis and for adults receiving prophylaxis. Fever was the most commonly observed clinical sign at baseline (16 children [88.9%] and 31 adults [31%]) and hematologic malignancy was the most frequent primary diagnosis at admission (11 children [61.1%] and 40 adults [40%]). Candida species were the most commonly identified causal agents of invasive fungal infections (2 children [11.1%] and 48 adults [48%]).
CONCLUSIONS
The efficacy and safety profiles of micafungin use in Slovenia and Romania based on clinician's own experiences in local clinical practice were consistent with those reported in other real-world studies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Candidiasis; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Infant; Infant, Newborn; Male; Micafungin; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Romania; Slovenia; Young Adult
PubMed: 34242200
DOI: 10.3855/jidc.12755 -
The Journal of Veterinary Medical... Jul 2022In this study, we isolated eight strains of Candida albicans from the blowhole air cultures of eight dolphins (one Pacific white-sided dolphin and seven bottlenose...
In this study, we isolated eight strains of Candida albicans from the blowhole air cultures of eight dolphins (one Pacific white-sided dolphin and seven bottlenose dolphins) housed at the Enoshima Aquarium. The minimum inhibitory concentrations of antifungals for these isolates were determined by conducting E-test and broth microdilution assays using the CLSI M27-A3 protocol antifungal susceptibility testing method. Only one of the eight dolphins from which Candida had been isolated had been treated with amphotericin B (AMB), and four had been treated with itraconazole (ITZ). All isolates were identified as Candida albicans, and all were resistant to both ITZ and voriconazole, though the isolates exhibited susceptibility to AMB and micafungin. Based on our findings, we suspect that the frequency of occurrence of azole-resistant Candida species is increasing in captive dolphins as well as in their aquarium environments.
Topics: Animals; Antifungal Agents; Candida; Candida albicans; Dolphins; Drug Resistance, Fungal; Itraconazole; Microbial Sensitivity Tests; Voriconazole
PubMed: 35598982
DOI: 10.1292/jvms.22-0007