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Journal of Enzyme Inhibition and... Dec 2022With increasing number of immunocompromised patients as well as drug resistance in fungi, the risk of fatal fungal infections in humans increases as well. The action of... (Review)
Review
With increasing number of immunocompromised patients as well as drug resistance in fungi, the risk of fatal fungal infections in humans increases as well. The action of echinocandins is based on the inhibition of β-(1,3)-d-glucan synthesis that builds the fungal cell wall. Caspofungin, micafungin, anidulafungin and rezafungin are semi-synthetic cyclic lipopeptides. Their specific chemical structure possess a potential to obtain novel derivatives with better pharmacological properties resulting in more effective treatment, especially in infections caused by and species. In this review we summarise information about echinocandins with closer look on their chemical structure, mechanism of action, drug resistance and usage in clinical practice. We also introduce actual trends in modification of this antifungals as well as new methods of their administration, and additional use in viral and bacterial infections.
Topics: Antifungal Agents; Aspergillus; Candida; Cell Wall; Drug Design; Echinocandins; Glucans; Microbial Sensitivity Tests; Molecular Structure
PubMed: 35296203
DOI: 10.1080/14756366.2022.2050224 -
Virulence Dec 2022Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and... (Review)
Review
Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and antifungal susceptibility pattern is necessary to control and treat candidiasis. We aimed to systematically analyse the susceptibility profiles of species published in the last ten years (December 2011 to December 2021) from mainland China. The studies were collected from PubMed, Google Scholar, and Science Direct search engines. Out of 89 included studies, a total of 44,716 isolates were collected, mainly comprising (49.36%), (21.89%), (13.92%), and (11.37%). The lowest susceptibility was detected for azole group; fluconazole susceptibilities against , and were 93.25%, 91.6%, 79.4%, 77.95%, 76%, 50%, and 0% respectively. Amphotericin B and anidulafungin were the most susceptible drugs for all species. Resistance to azole was mainly linked with mutations in , and genes. Mutation in and in and causing resistance to echinocandins was stated in two studies. Gaps in the studies' characteristics were detected, such as 79.77%, 47.19 %, 26.97%, 7.86%, and 4.49% studies did not mention the mortality rates, age, gender, breakpoint reference guidelines, and fungal identification method, respectively. The current study demonstrates the overall antifungal susceptibility pattern of species, gaps in surveillance studies and risk-reduction strategies that could be supportive in candidiasis therapy and for the researchers in their future studies.
Topics: Humans; Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidiasis; Echinocandins; Fluconazole; Microbial Sensitivity Tests
PubMed: 36120738
DOI: 10.1080/21505594.2022.2123325 -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2019Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and... (Review)
Review
BACKGROUND
Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation.
MATERIAL AND METHODS
Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library.
RESULTS
Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides.
CONCLUSIONS
Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.
Topics: Administration, Intravenous; Administration, Oral; Administration, Topical; Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candidiasis, Oral; Caspofungin; Clotrimazole; Databases, Factual; Drug Interactions; Echinocandins; Fluconazole; Humans; Miconazole; Nitriles; Nystatin; Pyridines; Triazoles
PubMed: 30818309
DOI: 10.4317/medoral.22978 -
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 -
The Journal of Antimicrobial... May 2022Increased fluconazole and echinocandin resistance in Candida glabrata requires prompt detection in routine settings. A phenotypic test based on the EUCAST E.DEF 7.3.2...
BACKGROUND
Increased fluconazole and echinocandin resistance in Candida glabrata requires prompt detection in routine settings. A phenotypic test based on the EUCAST E.DEF 7.3.2 protocol was developed for the detection of fluconazole- and anidulafungin-resistant isolates utilizing the colorimetric dye XTT.
METHODS
Thirty-one clinical C. glabrata isolates, 11 anidulafungin resistant and 14 fluconazole resistant, were tested. After optimization studies, 0.5-2.5 × 105 cfu/mL of each isolate in RPMI 1640 + 2% d-glucose medium containing 100 mg/L XTT + 0.78 μΜ menadione and 0.06 mg/L anidulafungin (S breakpoint) or 16 mg/L fluconazole (I breakpoint) in 96-well flat-bottom microtitration plates were incubated at 37°C for 18 h; we also included drug-free wells. XTT absorbance was measured at 450 nm every 15 min. Differences between the drug-free and the drug-treated wells were assessed using Student's t-test at different timepoints. ROC curves were used in order to identify the best timepoint and cut-off.
RESULTS
The XTT absorbance differences between fluconazole-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible increased exposure isolates (0.08 ± 0.05 versus 0.25 ± 0.06, respectively, P = 0.005) at 7.5 h, with a difference of <0.157 corresponding to 100% sensitivity and 94% specificity for detection of resistance. The XTT absorbance differences between anidulafungin-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible isolates (0.08 ± 0.07 versus 0.200 ± 0.03, respectively, P < 0.001) at 5 h, with a difference of <0.145 corresponding to 91% sensitivity and 100% specificity, irrespective of underlying mutations.
CONCLUSIONS
A simple, cheap and fast phenotypic test was developed for detection of fluconazole- and anidulafungin-resistant C. glabrata isolates.
Topics: Anidulafungin; Antifungal Agents; Candida glabrata; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; Microbial Sensitivity Tests
PubMed: 35323941
DOI: 10.1093/jac/dkac075 -
Frontiers in Pharmacology 2022We aimed to estimate the risk of drug-induced liver injury (DILI) from various antifungal treatments with azoles and echinocandins causing in real-world practice. We...
We aimed to estimate the risk of drug-induced liver injury (DILI) from various antifungal treatments with azoles and echinocandins causing in real-world practice. We performed disproportionality and Bayesian analyses based on data from the first quarter in 2004 to the third quarter in 2021 in the Food and Drug Administration Adverse Event Reporting System to characterize the signal differences of antifungal drugs-related DILI. We also compared the onset time and mortality differences of different antifungal agents. A total of 2943 antifungal drugs-related DILI were identified. Affected patients tended to be aged >45 years (51.38%), with more males than females (49.03% vs. 38.09%). Antifungal drug-induced liver injury is most commonly reported with voriconazole (32.45%), fluconazole (19.37%), and itraconazole (14.51%). Almost all antifungal drugs were shown to be associated with DILI under disproportionality and Bayesian analyses. The intraclass analysis of correlation between different antifungal agents and DILI showed the following ranking: caspofungin (ROR = 6.12; 95%CI: 5.36-6.98) > anidulafungin (5.15; 3.69-7.18) > itraconazole (5.06; 4.58-5.60) > voriconazole (4.58; 4.29-4.90) > micafungin (4.53; 3.89-5.27) > posaconazole (3.99; 3.47-4.59) > fluconazole (3.19; 2.93-3.47) > ketoconazole (2.28; 1.96-2.64). The onset time of DILI was significantly different among different antifungal drugs ( < 0.0001), and anidulafungin result in the highest mortality rate (50.00%), while ketoconazole has the lowest mortality rate (9.60%). Based on the Food and Drug Administration Adverse Event Reporting System database, antifungal drugs are significantly associated with DILI, and itraconazole and voriconazole had the greatest risk of liver injury. Due to indication bias, more clinical studies are needed to confirm the safety of echinocandins.
PubMed: 35571077
DOI: 10.3389/fphar.2022.891336 -
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 -
BMC Medicine Oct 2022The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious...
BACKGROUND
The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment.
METHODS
The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis.
RESULTS
Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1.
CONCLUSIONS
The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.
Topics: Animals; Mice; Anidulafungin; Antifungal Agents; Antiviral Agents; Bunyaviridae Infections; Clathrin; Receptor, Interferon alpha-beta; SARS-CoV-2; Viral Proteins; Virus Diseases
PubMed: 36266654
DOI: 10.1186/s12916-022-02558-z