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IDCases 2019A 37-year-old African American male with a past medical history significant for end stage renal disease on hemodialysis via a femoral arteriovenous graft, systemic lupus...
A 37-year-old African American male with a past medical history significant for end stage renal disease on hemodialysis via a femoral arteriovenous graft, systemic lupus erythematous, with a recent hospitalization for cavitary Candida pneumonia treated with micafungin, presented with a fever of 102° F for 3 days and worsening left groin pain. He also complained of chills, nausea, and malaise. On physical examination, the patient was hemodynamically stable with swelling and tenderness at the site of the graft. He was started on vancomycin, piperacillin/tazobactam and micafungin. Computed tomography scan and duplex scan of the left lower extremity showed diffuse swelling and attenuation of the graft material consistent with thrombosis of the graft. Excision of the graft and thrombectomy was performed and the graft thrombus was sent for culture. Examination of the sample showed fungal hyphae (Figure). Micafungin was switched to voriconazole; however, the patient did not show any improvement of his groin pain. On day 5 of hospitalization, culture showed , and hence amphotericin B was added resulting in subsequent clinical improvement. We are presenting an unusual site of infection which responded to combination therapy, a case which has not been reported.
PubMed: 30847281
DOI: 10.1016/j.idcr.2019.e00511 -
Annals of the New York Academy of... Sep 2015Fungal infections due to Candida and Aspergillus species cause extensive morbidity and mortality, especially among immunosuppressed patients, and antifungal therapy is... (Review)
Review
Fungal infections due to Candida and Aspergillus species cause extensive morbidity and mortality, especially among immunosuppressed patients, and antifungal therapy is critical to patient management. Yet only a few drug classes are available to treat invasive fungal diseases, and this problem is compounded by the emergence of antifungal resistance. Echinocandin drugs are the preferred choice to treat candidiasis. They are the first cell wall-active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer. Therapeutic failures occur rarely among common Candida species, with the exception of Candida glabrata, which is frequently multidrug resistant. Echinocandin resistance in susceptible species is always acquired during therapy. The mechanism of resistance involves amino acid changes in hot-spot regions of Fks subunits of glucan synthase, which decrease the sensitivity of the enzyme to drug. Cellular stress response pathways lead to drug adaptation, which promotes the formation of resistant fks strains. Clinical factors promoting echinocandin resistance include empiric therapy, prophylaxis, gastrointestinal reservoirs, and intra-abdominal infections. A better understanding of the echinocandin-resistance mechanism, along with cellular and clinical factors promoting resistance, will facilitate more effective strategies to overcome and prevent echinocandin resistance.
Topics: Antifungal Agents; Candida albicans; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Echinocandins; Glucosyltransferases; Humans; Species Specificity; beta-Glucans
PubMed: 26190298
DOI: 10.1111/nyas.12831 -
Journal of Applied Microbiology Dec 2016Increase in invasive fungal infections over the past few years especially in immunocompromised patients prompted the search for new antifungal agents with improved... (Review)
Review
Increase in invasive fungal infections over the past few years especially in immunocompromised patients prompted the search for new antifungal agents with improved efficacy. Current antifungal armoury includes very few effective drugs like Amphotericin B; new generation azoles, including voriconazole and posaconazole; echinocandins like caspofungin and micafungin to name a few. Azole class of antifungals which target the fungal cell membrane are the first choice of treatment for many years because of their effectiveness. As the fungal cell membrane is predominantly made up of sterols, glycerophospholipids and sphingolipids, the role of lipids in pathogenesis and target identification for improved therapeutics were largely pursued by researchers during the last few years. Present review focuses on cell membrane as an antifungal target with emphasis on membrane biogenesis, structure and function of cell membrane, cell membrane inhibitors, screening assays, recent advances and future prospects.
Topics: Antifungal Agents; Azoles; Cell Membrane; Fungi; Humans; Mycoses
PubMed: 27667746
DOI: 10.1111/jam.13301 -
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 -
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 -
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 -
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 -
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 -
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 -
Indian Journal of Medical Microbiology 2018The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting.... (Review)
Review
The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting. However, apart from bacterial infections rising in hospitals, the incidences of fungal infections are growing with the development of resistance to conventional antifungal agents. Newer antifungal agents such as echinocandins (ECs) have been extensively studied over the past decade and are recognised as a superior treatment compared with prior antifungals as a first line of therapy in tertiary institutions. Caspofungin (CAS), micafungin (MICA) and anidulafungin (ANID) are the three most widely used EC antifungal agents. The treatment of biofilm-associated fungal infections affecting patients in tertiary health-care facilities has been identified as a challenge, particularly in Indian Intensive Care Unit (ICU) settings. With the rising number of critically ill patients requiring invasive devices such as central venous catheters for treatment, especially in ICUs, these devices serve as a potential source of nosocomial infections. Candida spp. colonisation is a major precursor of these infections and further complicates and prolongs treatment procedures, adding to increasing costs both for hospitals and the patient. Analysing studies involving the use of these agents can help in making critical decisions for antifungal therapy in the event of a fungal infection in the ICU. In addition, the development of resistance to antifungal agents is a crucial factor for assessing the appropriate antifungals that can be used for treatment. This review provides an overview of ANID in biofilms, along with CAS and MICA, in terms of clinical efficacy, resistance development and potency, primarily against Candida spp.
Topics: Anidulafungin; Antifungal Agents; Biofilms; Candida; Candidiasis; Caspofungin; Critical Illness; Cross Infection; Drug Resistance, Fungal; Echinocandins; Humans; Intensive Care Units; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Tertiary Healthcare
PubMed: 29735833
DOI: 10.4103/ijmm.IJMM_17_400