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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 -
International Journal of Antimicrobial... Feb 2024The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting...
BACKGROUND AND OBJECTIVE
The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting of ECMO support, invasive fungal infections are a severe cause of morbidity and mortality. This vulnerable population is at risk of suboptimal antifungal exposure due to an increased volume of distribution (Vd), drug sequestration and decreased clearance. Here, we aimed to summarize ex-vivo and clinical studies on the potential impact of ECMO on the pharmacokinetics (PK) of antifungal agents and dosing requirements.
METHODS
A systematic search of the literature within electronic databases PubMed and EMBASE was conducted from database inception to 30 April 2023. Inclusion criteria were as follows: critically ill patients receiving ECMO regardless of age and reporting at least one PK parameter.
RESULTS
Thirty-six studies met inclusion criteria, including seven ex-vivo experiments and 29 clinical studies evaluating three classes of antifungals: polyenes, triazoles and echinocandins. Based on the available ex-vivo PK data, we found a significant sequestration of highly lipophilic and protein-bound antifungals within the ECMO circuit such as voriconazole, posaconazole and micafungin but the PK of several antifungals remains to be addressed such as amphotericin B, isavuconazole and anidulafungin. Most clinical studies have shown increased Vd of some antifungals like fluconazole and micafungin, particularly in the pediatric population. Conflicting data exist about caspofungin exposure.
CONCLUSIONS
The available literature on the antifungal PK changes in ECMO setting is scarce. Whenever possible, therapeutic drug monitoring is highly advised to personalize antifungal therapy.
Topics: Humans; Antifungal Agents; Caspofungin; Critical Illness; Extracorporeal Membrane Oxygenation; Micafungin
PubMed: 38161046
DOI: 10.1016/j.ijantimicag.2023.107078 -
The Journal of Infection Nov 2023The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the...
The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25-33%) while Italy and Turkey had the highest C. parapsilosis proportions (24-26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.
PubMed: 37549695
DOI: 10.1016/j.jinf.2023.08.001 -
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 -
Applied Microbiology and Biotechnology Jan 2021Echinocandins are a clinically important class of non-ribosomal antifungal lipopeptides produced by filamentous fungi. Due to their complex structure, which is... (Review)
Review
Echinocandins are a clinically important class of non-ribosomal antifungal lipopeptides produced by filamentous fungi. Due to their complex structure, which is characterized by numerous hydroxylated non-proteinogenic amino acids, echinocandin antifungal agents are manufactured semisynthetically. The development of optimized echinocandin structures is therefore closely connected to their biosynthesis. Enormous efforts in industrial research and development including fermentation, classical mutagenesis, isotope labeling, and chemical synthesis eventually led to the development of the active ingredients caspofungin, micafungin, and anidulafungin, which are now used as first-line treatments against invasive mycosis. In the last years, echinocandin biosynthetic gene clusters have been identified, which allowed for the elucidation but also engineering of echinocandin biosynthesis on the molecular level. After a short description of the history of echinocandin research, this review provides an overview of the current knowledge of echinocandin biosynthesis with a special focus of the diverse structural elements, their biosynthetic background, and structure-activity relationships. KEY POINTS: • Complex and highly oxidized lipopeptides produced by fungi. • Crucial in the design of drugs: side chain, solubility, and hydrolytic stability. • Genetic methods for engineering biosynthesis have recently become available.
Topics: Antifungal Agents; Echinocandins; Fungi; Lipopeptides; Microbial Sensitivity Tests; Multigene Family
PubMed: 33270153
DOI: 10.1007/s00253-020-11022-y -
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 -
Contact in Context 2022Intra-lot and inter-lot variability in the spectra of micafungin was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR)....
Intra-lot and inter-lot variability in the spectra of micafungin was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Two vials of 6 vials sampled from Fresenius Kabi lot ACP106 appeared 7.9 and 14.0 standard deviations (SDs) from the center of the rest of the vials on the DQS FTNIR screening assay. Spectra of 48 vials from 7 lots in the library showed 2 outliers at 8.3 and 9.8 SDs from the center of the rest of the library, suggesting they represent different material.
PubMed: 35360460
DOI: 10.6084/m9.figshare.19071704 -
3 Biotech Jul 2023The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered... (Review)
Review
The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera , , and . There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.
PubMed: 37309405
DOI: 10.1007/s13205-023-03648-2 -
Journal of Fungi (Basel, Switzerland) Dec 2021In different regions worldwide, there exists an intra-and inter-regional variability in the rates of resistance to antifungal agents in , highlighting the importance of... (Review)
Review
In different regions worldwide, there exists an intra-and inter-regional variability in the rates of resistance to antifungal agents in , highlighting the importance of understanding the epidemiology and antifungal susceptibility profiles of in each region. However, in some regions, such as Ibero-America, limited data are available in this context. Therefore, in the present study, a systematic review was conducted to determine the antifungal resistance in in Ibero-America over the last five years. A literature search for articles published between January 2015 and December 2020 was conducted without language restrictions, using the PubMed, Embase, Cochrane Library, and LILACS databases. The search terms that were used were "" AND "antifungal resistance" AND "Country", and 22 publications were retrieved from different countries. The use of azoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, and miconazole) varied between 4.0% and 100%, and that of echinocandins (micafungin, caspofungin, and anidulafungin) between 1.1% and 10.0%. The limited information on this subject in the region of Ibero-America emphasizes the need to identify the pathogens at the species level and perform antifungal susceptibility tests that may lead to the appropriate use of these drugs and the optimal doses in order to avoid the development of antifungal resistance or multi-resistance.
PubMed: 35049954
DOI: 10.3390/jof8010014 -
Medical Mycology Sep 2022The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are... (Observational Study)
Observational Study
Distribution, trends, and antifungal susceptibility of Candida species causing candidemia in Japan, 2010-2019: A retrospective observational study based on national surveillance data.
The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from > 2000 hospitals for the 2010-2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P < 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P < 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance.
Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidemia; Drug Resistance, Fungal; Fluconazole; Humans; Japan; Micafungin; Microbial Sensitivity Tests; Voriconazole
PubMed: 36095139
DOI: 10.1093/mmy/myac071