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Pathogens (Basel, Switzerland) Mar 2024(1) Background: Despite being considered a non-pathogenic yeast, recently, a growing occurrence of infections has been noted. There is little knowledge about the drug...
(1) Background: Despite being considered a non-pathogenic yeast, recently, a growing occurrence of infections has been noted. There is little knowledge about the drug susceptibility of this species. Therefore, the objective of this research was to expand it and determine the drug susceptibility profile of a local collection of clinical isolates of this species. (2) Methods: This study contained 55 clinical isolates identified as using the MALDI-TOF method. The susceptibility of was tested to 10 antifungals (amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole, micafungin, anidulafungin, caspofungin, and itraconazole) using MICRONAUT-AT tests and manogepix, a new drug, using the microdilution method according to EUCAST. (3) Results: Overall, most strains were classified as sensitive to amphotericin B and flucytosine (MIC ranges of ≤0.03-1 and ≤0.06-0.125, respectively) and also to echinocandins. However, five isolates expressed high MIC values for all of the tested azoles, indicating cross-resistance. The MIC range for manogepix was 0.001-0.125 mg/L, with an MIC of 0.03 mg/L and an MIC of 0.06 mg/L. (4) Conclusions: The occurrence of resistance to azoles may be a concerning problem and therefore should be investigated further. However, the new antifungal manogepix appears to be an interesting new therapeutic option for treating such infections.
PubMed: 38535591
DOI: 10.3390/pathogens13030248 -
Enfermedades Infecciosas Y... Dec 2023Biofilm formation causes virulence and resistance in Candida albicans. However, little is known about breakthrough candidemia isolates. We evaluated the antifungal...
Comparison of amphotericin B lipid complex, deoxycholate amphotericin B, fluconazole, and anidulafungin activity against Candida albicans biofilm isolated from breakthrough candidemia.
INTRODUCTION
Biofilm formation causes virulence and resistance in Candida albicans. However, little is known about breakthrough candidemia isolates. We evaluated the antifungal activity of fluconazole, anidulafungin, deoxycholate amphotericin B (dAMB), and amphotericin B lipid complex (ABLC) against biofilms of C. albicans isolated from patients with breakthrough candidemia.
METHODS
The present study used strains of C. albicans isolated from breakthrough and non-breakthrough candidemia patients (control group). The susceptibility of planktonic cells to amphotericin B, anidulafungin, and fluconazole was determined by broth microdilution. Antifungal activity in sessile cells was evaluated using the minimum biofilm eradication concentration (MBEC), metabolic activity was estimated by reducing MTT, and biomass was estimated using crystal violet retention.
RESULTS
The planktonic strains were susceptible to amphotericin B, anidulafungin, and fluconazole, with minimum inhibitory concentrations of 1, ≤0.03, and 2mg/L, respectively. However, fluconazole and anidulafungin did not exert an antifungal effect on biofilms. Additionally, dAMB and ABCL reduced the metabolic activity and biomass. However, eradication was only achieved using 16mg/L dAMB. C. albicans isolates of breakthrough candidemia exhibited strong biofilm production, and the in vitro activity of available therapeutic options was poor.
CONCLUSION
In the present study, only dAMB and ABCL exhibited antibiofilm effects against sessile breakthrough candidemia isolates.
Topics: Humans; Amphotericin B; Antifungal Agents; Anidulafungin; Fluconazole; Candida albicans; Candidemia; Candida; Biofilms; Deoxycholic Acid
PubMed: 36707288
DOI: 10.1016/j.eimce.2022.07.009 -
Antimicrobial Agents and Chemotherapy Feb 2024Invasive candidiasis is a major hospital-acquired infection. Usually, echinocandins are considered first-line treatment. However, resistant phenotypes have emerged....
Invasive candidiasis is a major hospital-acquired infection. Usually, echinocandins are considered first-line treatment. However, resistant phenotypes have emerged. Ibrexafungerp (IBX) is a new antifungal substance with potent anti- activity. We challenged IBX with a library of 192 pheno-/genotypically echinocandin-resistant isolates, focusing on the substance susceptibility, its activity on certain hotspot (HS) mutated strains, and applying WTULs (wild-type upper limits). Therefore, a 9-year-old strain and patient data collection provided by the German National Reference Center for Invasive Fungal Infections were analyzed. Species identification was confirmed through ITS-sequencing. Molecular susceptibility testing was performed by sequencing HS of the gene. Anidulafungin (AND) and IBX EUCAST-broth-microdilution was conducted. The four most common echinocandin-resistance mediating mutations were found in [112/192 isolates; F659-(43×) and S663-(48×)] and [63/192 isolates; F641-(15×) and S645-(39×)]. Mutations at the HS-start sequence were associated with higher IBX MIC-values (F659 and F641 (MIC 50/90 mg/L: >4/>4 and 2/4 mg/L) in comparison to AND (F659 and F641 (MIC 50/90: 1/4 and 0.25/1 mg/L). MIC-values in HS-center mutations were almost equal [MIC50/90 in S663: 2/4 (AND and IBX); in S645: 0.5/1 (AND) and 0.25/1 (IBX) mg/L]. In total, 61 vs 78 of 192 echinocandin-resistant isolates may be classified as IBX wild type by applying WTULs, whereas the most prominent effect was seen in [48% (30/63) vs 70% (44/63)]. IBX shows activity against echinocandin-resistant and thus is an addition to the antifungal armory. However, our data suggest that this effect is more pronounced in and strains harboring mutations, affecting the HS-center.
Topics: Humans; Child; Echinocandins; Antifungal Agents; Candida; Glycosides; Candida albicans; Candida glabrata; Microbial Sensitivity Tests; Drug Resistance, Fungal; Triterpenes
PubMed: 38206004
DOI: 10.1128/aac.01324-23 -
Current Medical Mycology Sep 2023Onychomycosis caused by dematiaceous fungi is rarely reported and the identification is also quite tricky due to poor sporulation. Recent emergence of dematiaceous fungi...
BACKGROUND AND PURPOSE
Onychomycosis caused by dematiaceous fungi is rarely reported and the identification is also quite tricky due to poor sporulation. Recent emergence of dematiaceous fungi as a major cause of onychomycosis is a matter of concern in the field of mycology. Therefore, this study aimed to understand the dematiaceous fungi as a possible cause of onychomycosis, especially among agricultural workers. In addition, the evaluation of the antifungal susceptibility patterns led to the idea of an accurate drug that will help to treat and prevent antifungal resistance.
MATERIALS AND METHODS
The standard procedure was followed for direct microscopic examination and fungi isolation. Furthermore, antifungal susceptibility testing was conducted in accordance with the Clinical and Laboratory Standards Institute M-38-A2 protocol.
RESULTS
Both potassium hydroxide and fungal positivity were found in 275 out of 356 suspected cases, 52%, 4.3%, 28.7%, and 14.9% of which were non-dermatophytic molds (NDMs), yeast, dermatophytes, and sterile hyphae, respectively. Among NDMs (52%, n=143), 45.5% (n=65) were hyaline hyphomycetes and 54.5% (n=78) were dematiaceous hyphomycetes. Among dematiaceous fungi, spp. and spp. were the commonly isolated ones. Additionally, azoles, amphotericin-B, and anidulafungin showed excellent antifungal activity against tested isolates.
CONCLUSION
Dematiaceous fungi are now becoming a potential cause of onychomycosis. A more detailed study is needed on the identification of these emerging isolates and the mode of action of antifungal drugs for a better treatment strategy.
PubMed: 38361959
DOI: 10.22034/cmm.2023.345077.1428 -
Antibiotics (Basel, Switzerland) Aug 2023Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive...
Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive in comparison with the relatively low rates of bacterial coinfection. Although patients who are critically ill with COVID-19 may be at an increased risk for pulmonary aspergillosis, antifungal use in these populations remained underreported, particularly in later phases of the pandemic. This single-center, population-level cohort analysis compares the monthly use rates of mold-active antifungal drugs in the medical intensive care unit during April 2019-March 2020 (baseline) with those during April 2020-November 2022. The antifungal drugs included in the analysis were liposomal amphotericin B, anidulafungin, isavuconazonium, posaconazole, and voriconazole. We found that during 2020-2022, the usage of antifungal drugs was not significantly different from baseline for all included agents except isavuconazonium, which was used significantly more ( = 0.009). There were no changes in diagnostic modalities between the two time periods. The reported prevalence of and mortality from COVID-19-associated pulmonary aspergillosis (CAPA) may have resulted in higher rates of prescribing antifungal drugs for critically ill patients with COVID-19. Antimicrobial stewardship programs should develop and apply tools to facilitate more effective and appropriate antifungal use.
PubMed: 37760649
DOI: 10.3390/antibiotics12091352 -
Microbiology Spectrum Sep 2023Members of the species complex are able to cause superficial and life-threatening systemic infections with low susceptibility to azoles and echinocandins. We tested 130...
Members of the species complex are able to cause superficial and life-threatening systemic infections with low susceptibility to azoles and echinocandins. We tested 130 bloodstream complex isolates collected from eight Latin American medical centers over 18 years (period 1 = 2000-2008 and period 2 = 2009-2018) to investigate trends in species distribution and antifungal resistance. The isolates were identified by rDNA ITS region sequencing, and antifungal susceptibility tests were performed against fluconazole, voriconazole, anidulafungin, and amphotericin B using the CLSI microbroth method. (s.s.; = 116) was the most prevalent species, followed by ( = 12) and ( = 2). Based on rDNA ITS identification, three clades within were characterized (clade 1 = 94; clade 2 = 19; and clade 3 = 3). In the second period of study, we found a substantial increment in the isolation of (3.4% versus 13.8%; = 0.06) and clade 2 s.s. exhibiting lower susceptibility to one or more triazoles. IMPORTANCE Yeast-invasive infections play a relevant role in human health, and there is a concern with the emergence of non- pathogens causing disease worldwide. There is a lack of studies addressing the prevalence and antifungal susceptibility of different species within the complex that cause invasive infections. We evaluated 130 episodes of species complex candidemia documented in eight medical centers over 18 years. We detected the emergence of less common species within the complex causing candidemia and described a new clade of with limited susceptibility to triazoles. These results support the relevance of continued global surveillance efforts to early detect, characterize, and report emergent fungal pathogens exhibiting limited susceptibility to antifungals.
PubMed: 37698428
DOI: 10.1128/spectrum.05115-22 -
Journal of Fungi (Basel, Switzerland) May 2024The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison...
The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical isolates (including 400 , 200 , 200 , 150 and 50 ) and 150 isolates (100 and 50 ) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common species. exhibited higher resistance rates (about 8.67-40.67% in different antifungals) than the other four species. Through the sequencing of genes, we searched for mutations in echinocandin-resistant isolates and found that all displayed alterations in S654P. The determined MEC (minimal effective concentration) values against and for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common and species. Rezafungin showed higher susceptibility rates against . Rezafungin indicates its potent activity for potential clinical application.
PubMed: 38921383
DOI: 10.3390/jof10060397 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Oct 2023To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive isolates from 2017 to 2021 in East China....
To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive isolates from 2017 to 2021 in East China. Using a retrospective analysis, the East China Invasive Fungal Infection Group (ECIFIG) collected clinically isolated from 32 hospitals in East China between January 2017 and December 2021. The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital. The minimum inhibitory concentrations (MICs) of the strains against fluconazole (FLU), voriconazole (VOR), itraconazole (ITR), Posaconazole (POS), isavuconazole (ISA), anidulafungin (ANI), caspofungin (CAS), micafungin (MICA) and 5-fluorocytosine (FCT) were tested by the ThermoFisher CMC1JHY colorimetric microdilution method. The MIC of amphotericin B (AMB) was tested by the broth microdilution method. The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values (ECV) published by the Clinical and Laboratory Standards Institute (CLSI) M27 Ed3 and M57 Ed4 documents. Data analysis was conducted using the Kruskal-Wallis test and paired -test. In total, 305 isolates were collected. There were 38.0% (116/305) strains isolated from blood, 11.5% (35/305) ascites, 8.9% (27/305) catheter and 8.9% (27/305) drainage fluid. The resistance rate of to FLU was 32.5%, to VOR was 28.5%, and the cross-resistance rate to FLU and VOR was 28.5%. The wild-type proportions for ITR and POS were 79.3% and 29.2% respectively. There was no significant difference in resistance rates, MIC, and MIC of FLU and VOR, or in the wild-type rates of ITR and POS over five years. More than 95.0% of the isolates were susceptible to echinocandins. However, one strain was identified as being multi-drug resistant. In azole antifungals, voriconazole, itraconazole, posaconazole, and isavuconazole have similar GM MIC values. The GM MIC of fluconazole is significantly higher than that of itraconazole (=9.95, <0.05), posaconazole (=9.99, <0.05), and voriconazole (=10.01, <0.05), Meanwhile, among echinocandins, the GM MIC of ANI was comparable to that of CAS (=1.17, >0.05), both of which were significantly higher than MICA (=11.56, <0.05; =4.15, <0.05). The clinical isolates of in East China from 2017 to 2021 were relatively susceptible to echinocandins. However, there was consistently high resistance to fluconazole and voriconazole. More intensive efforts should be made on the monitoring of drug resistance in .
Topics: Humans; Antifungal Agents; Fluconazole; Candida tropicalis; Voriconazole; Itraconazole; Retrospective Studies; Candida; China; Echinocandins; Microbial Sensitivity Tests
PubMed: 37859369
DOI: 10.3760/cma.j.cn112150-20221011-00984 -
Cureus Jul 2023We present a case of a 57-year-old male patient with a history of prolonged intensive care unit (ICU) stay for coronavirus disease 2019 (COVID-19) who developed fungal...
We present a case of a 57-year-old male patient with a history of prolonged intensive care unit (ICU) stay for coronavirus disease 2019 (COVID-19) who developed fungal spondylodiscitis, a rare complication. The patient initially presented complaining of respiratory symptoms and was subsequently treated with tocilizumab, remdesivir, enoxaparin, and dexamethasone. Following ICU discharge, he experienced recurrent infections, including extended-spectrum beta-lactamase urinary tract infection. Two months later, he developed back pain; magnetic resonance imaging (MRI) revealed inflammatory spondylodiscitis. Despite empirical antibiotic therapy, his condition did not improve, and a bone biopsy confirmed infection. Antifungal treatment with fluconazole and anidulafungin resulted in a significant clinical improvement. The patient achieved complete recovery after six months of therapy. This case highlights the rare occurrence of fungal spondylodiscitis in COVID-19 patients with a history of ICU stay and emphasizes the importance of early recognition and appropriate management to mitigate potential complications.
PubMed: 37602130
DOI: 10.7759/cureus.42079 -
The Biochemical Journal Jul 2023Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its...
Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification of drug-targets/candidates or to repurpose existing drugs against known targets through drug repurposing. Repurposing of drugs has gained traction recently where orphan drugs are exploited for new indications. In the current study, we have combined drug repurposing with polypharmacological targeting approach to modulate structure-function of multiple proteins in M. tb. Based on previously established essentiality of genes in M. tb, four proteins implicated in acceleration of protein folding (PpiB), chaperone assisted protein folding (MoxR1), microbial replication (RipA) and host immune modulation (S-adenosyl dependent methyltransferase, sMTase) were selected. Genetic diversity analyses in target proteins showed accumulation of mutations outside respective substrate/drug binding sites. Using a composite receptor-template based screening method followed by molecular dynamics simulations, we have identified potential candidates from FDA approved drugs database; Anidulafungin (anti-fungal), Azilsartan (anti-hypertensive) and Degarelix (anti-cancer). Isothermal titration calorimetric analyses showed that the drugs can bind with high affinity to target proteins and interfere with known protein-protein interaction of MoxR1 and RipA. Cell based inhibitory assays of these drugs against M. tb (H37Ra) culture indicates their potential to interfere with pathogen growth and replication. Topographic assessment of drug-treated bacteria showed induction of morphological aberrations in M. tb. The approved candidates may also serve as scaffolds for optimization to future anti-mycobacterial agents which can target MDR strains of M. tb.
Topics: Drug Repositioning; Mycobacterium tuberculosis; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Anidulafungin; Bacterial Proteins; Protein Structure, Tertiary; Molecular Dynamics Simulation
PubMed: 37306466
DOI: 10.1042/BCJ20230143