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Mycopathologia Oct 2023The difficulties in the identification of C. auris and the delays in the implementation of infection control precautions contribute to outbreaks. This study analyzed 10...
BACKGROUND
The difficulties in the identification of C. auris and the delays in the implementation of infection control precautions contribute to outbreaks. This study analyzed 10 patients with COVID-19 and C. auris candidemia, their characteristic and clinical features and phylogenetic features, and the antifungal susceptibilities of the isolates.
METHOD
C. auris were detected in the COVID-19 ICU of a university hospital between January and August 2021. Identification to species level was performed using MALDI-TOF MS. Antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. The isolates were whole genome sequenced to assess genetic relatedness and a phylogenetic tree was drawn including various C. auris clades.
RESULTS
The mean growth time in blood cultures was 38.8 h. C. auris candidemia developed on the average 27th day of ICU admission. All were susceptible to anidulafungin and micafungin, while they were resistant to fluconazole and amphotericin B. Only three isolates were found to be resistant to caspofungin. All patients died. With the WGS method, all isolates were found in a close resemblance to each other in terms of total nucleotide similarity (with a minimum of 96% pairwise alignment). Our isolates showed the closest similarity to South Asian clade (Clade I).
CONCLUSIONS
This study is the first to evaluate the phylogenetic characteristics of C. auris using WGS and to determine antifungal susceptibilities in Türkiye on COVID-19 patients. The mortality rate was very high in patients who have both COVID-19 and C. auris candidemia.
PubMed: 37542203
DOI: 10.1007/s11046-023-00782-6 -
Medical Mycology Jul 2023Several institutions reported a rise not only in fungemia incidence but also in the number of cases caused by Candida auris or fluconazole-resistant C. parapsilosis...
Yeasts from blood cultures in the wake of the COVID-19 pandemic in a tertiary care hospital: Shift in species epidemiology, steady low antifungal resistance and full in vitro ibrexafungerp activity.
Several institutions reported a rise not only in fungemia incidence but also in the number of cases caused by Candida auris or fluconazole-resistant C. parapsilosis during the COVID-19 pandemic. Since the pandemic broke out in early 2020, we studied its impact on fungemia incidence, species epidemiology, potential patient-to-patient transmission, and antifungal resistance in 166 incident yeast isolates collected from January 2020 to December 2022. Isolates were molecularly identified, and their antifungal susceptibilities to amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp were studied following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method, and genotyped. The fungemia incidence (episodes per 1000 admissions) tended to decrease over time (2020 = 1.60, 2021 = 1.36, 2022 = 1.16); P > .05). Species distribution was C. albicans (50.6%, n = 84), C. parapsilosis (18.7%, n = 31), C. glabrata (12.0%, n = 20), C. tropicalis (11.4%, n = 19), C. krusei (3.0%, n = 5), other Candida spp. (1.2%, n = 2), and non-Candida yeasts (3.0%, n = 5). The highest and lowest proportions of C. albicans and C. parapsilosis were detected in 2020. The proportion of isolates between 2020 and 2022 decreased in C. albicans (60.3% vs. 36.7%) and increased in C. parapsilosis (10.3% vs. 28.6%; P < .05) and C. tropicalis (8.8% vs. 16.3%; P > .05). Only three C. albicans intra-ward clusters involving two patients each were detected, and the percentages of patients involved in intra-ward clusters reached 9.8% and 8.0% in 2020 and 2021, respectively, suggesting that clonal spreading was not uncontrolled. Fluconazole resistance (5%) exhibited a decreasing trend (P > .05) over time (2020 = 7.6%; 2021 = 4.2%; and 2022 = 2.1%). Ibrexafungerp showed high in vitro activity.
Topics: Animals; Antifungal Agents; Fluconazole; Pandemics; Fungemia; Blood Culture; Tertiary Care Centers; COVID-19; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Microbial Sensitivity Tests; Drug Resistance, Fungal
PubMed: 37460168
DOI: 10.1093/mmy/myad072 -
Infection and Drug Resistance 2023Candidemia and antifungal resistance are major healthcare challenges. The aim of this study is to describe the frequency of candidemia cases, distribution of spp., and...
PURPOSE
Candidemia and antifungal resistance are major healthcare challenges. The aim of this study is to describe the frequency of candidemia cases, distribution of spp., and the associated risk factors for mortality in an academic institution in Saudi Arabia over an 18-month period. We also evaluated the susceptibility patterns of blood isolates.
METHODS
Candidemia cases were collected from King Fahad Hospital of the University over the period between July 1st, 2020 through December 31st, 2021. They were prospectively reviewed for the preceding risk factors and antifungal (AF) susceptibility, testing results to fluconazole (FL), voriconazole (VO), itraconazole (IT), posaconazole (PO), caspofungin (CASP), anidulafungin (AND), micafungin (MYC), flucytosine (FLC) and amphotericin B (AMPB) using a broth microdilution kit (Sensititre™ YeastOne).
RESULTS
A total of 48 candidemia isolates were included that were isolated from 43 patients. The median age of cases was 62 ± 23.3 years (60.4% males and 83% ICU patients). Independent risk factors for mortality at 30 days in candidemia patients were age, COVID-19 co-infection, and use of tocilizumab. The most commonly isolated species were and (22.9% each) followed by (18.75%). AF resistance for ≥1 antifungal was detected in 39.3% of 33 cases tested, with no cross-resistance identified. Resistance rates for each AF were as follows: FL (18%), VO (6%), IT (6%), PO (9%) and AMPB (3%). No resistance was seen for echinocandins apart from one strain showing an intermediate result for CASP.
CONCLUSION
The study showed an overall high rate of non-, with the predominance of and , representing a therapeutic challenge. AF resistance rate was high which emphasizes the importance of continuing surveillance and providing accurate and reliable tools in the laboratories for rapid speciation and susceptibility testing.
PubMed: 37457797
DOI: 10.2147/IDR.S411865 -
Mycoses Oct 2023Scedosporiosis/lomentosporiosis is a globally emerging and crucial fungal infection. However, clinical data on Scedosporium/Lomentospora infections in Taiwan are scarce.
BACKGROUND
Scedosporiosis/lomentosporiosis is a globally emerging and crucial fungal infection. However, clinical data on Scedosporium/Lomentospora infections in Taiwan are scarce.
OBJECTIVES
This study aimed to explore the clinical characteristics of Scedosporium/Lomentospora-infected patients and evaluate the susceptibility of these isolates to antifungal agents.
METHODS
The clinical features of Scedosporium/Lomentospora-infected patients at a tertiary teaching hospital in Northern Taiwan between 2014 and 2021 were retrospectively reviewed; isolates from these patients were identified to species level for antifungal susceptibility testing.
RESULTS
Among 44 patients, 27 (61.4%) had scedosporiosis/lomentosporiosis, whereas 17 (38.6%) were colonised with Scedosporium/Lomentospora species. Scedosporium apiospermum was the main coloniser; scedosporiosis was primarily caused by S. boydii. Trauma history, steroid and immunosuppressant use were the most common risk factors for developing these infections. Among 27 patients with scedosporiosis/lomentosporiosis, one was lost to follow-up and seven (7/26, 26.9%) died. Most patients with S. apiospermum infection have a history of trauma, leading to cutaneous, bone and ocular infections. Pulmonary, sinus and disseminated infections and mortality were frequently reported in patients with S. boydii infection. Voriconazole's minimum inhibitory concentration was low for S. boydii, S. apiospermum and S. aurantiacum. Caspofungin, micafungin and anidulafungin were active against S. boydii and S. apiospermum. A potentially novel Scedosporium species was identified in this study, with distinct clinical manifestations and antifungal susceptibility.
CONCLUSIONS
At our centre, S. boydii is the main causative species of scedosporiosis; voriconazole could be the first-line treatment in Taiwan. Our study supports the importance of speciation, rather than only categorising these isolates into S. apiospermum species complex.
Topics: Humans; Antifungal Agents; Voriconazole; Scedosporium; Retrospective Studies; Taiwan; Ascomycota
PubMed: 37449538
DOI: 10.1111/myc.13632 -
Frontiers in Cellular and Infection... 2023The aim of this study is to identify the pathogen causing ocular infection in a Chinese patient and to describe its morphological characteristics.
OBJECTIVE
The aim of this study is to identify the pathogen causing ocular infection in a Chinese patient and to describe its morphological characteristics.
METHODS
Samples from the patient's intraoperative pus were collected for microscopic examination and culture. Morphology and drug sensitivities of the isolated fungus were analyzed. Ribosomal DNA (rDNA) sequencing was performed and blasted in GenBank.
RESULTS
A strain of fungi was repeatedly isolated from pus samples in different types of medium. No conidia were shown when the isolate cultured on normal PDA medium, whereas pseudoseptate thick-walled conidia were shown when cultured on medium containing leaf leachate. The results of BLAST and phylogenetic trees based on internal transcribed spacer, beta-tubulin, translation elongation factor 1-alpha, and RNA polymerase II gene demonstrated that the isolated fungus was . Minimum inhibitory concentration results of this organism were as follows: anidulafungin, 0.06 μg/ml; amphotericin B, 0.12 μg/ml; micafungin, 0.06 μg/ml; caspofungin, 0.5 μg/ml; 5-fluorocytosine, >64 μg/ml; posaconazole, 2 μg/ml; voriconazole, 0.25 μg/ml; itraconazole, 0.5 μg/ml; fluconazole, 64 μg/ml.
CONCLUSION
The case was infected with and led to eye suppurative endophthalmitis and blindness. Combined applications of morphological and molecular biology techniques facilitate accurate diagnosis of fungal infections.
Topics: Humans; Phylogeny; Ascomycota; Amphotericin B; Eye Infections
PubMed: 37448776
DOI: 10.3389/fcimb.2023.1160831 -
Microbial Genomics Jul 2023Invasive candida infections are significant infections that may occur in vulnerable patients with high rates of mortality or morbidity. Drug-resistance rates also appear...
Invasive candida infections are significant infections that may occur in vulnerable patients with high rates of mortality or morbidity. Drug-resistance rates also appear to be on the rise which further complicate treatment options and outcomes. The aims of this study were to describe the prevalence, molecular epidemiology, and genetic features of bloodstream isolates in a hospital setting. The resistance mechanisms towards the two most commonly administered antifungals, fluconazole and anidulafungin, were determined. Blood culture isolates between 1 January 2018 and 30 June 2021 positive for spp. were included. Susceptibility testing was performed using Etest. Whole-genome-sequencing was performed using Illumina NovaSeq with bioinformatics analysis performed. A total of 203 isolates were sequenced: 56 . 53 . , 44 . 36 . complex (consisting of and ), six . five . , and three . . A single cluster of azole-resistant and four clusters of isolates were observed, suggesting possible transmission occurring over several years. We found 11.3%, and 52.7 % of and , respectively, clustered with other isolates, suggesting exogenous sources may play a significant role of transmission, particularly for . The clusters spanned over several years suggesting the possibility of environmental reservoirs contributing to the spread. Limited clonality was seen for . Several sequence types appeared to be dominant for however the SNP differences varied widely, indicating absence of sustained transmission.
Topics: Humans; Tertiary Care Centers; Drug Resistance, Fungal; Antifungal Agents; Candidemia; Candida; Genomics
PubMed: 37440287
DOI: 10.1099/mgen.0.001047 -
Medical Mycology Jul 2023In vitro interactions between tacrolimus, a calcineurin inhibitor, and fluconazole, itraconazole, caspofungin, or anidulafungin were evaluated against Candida auris, C....
In vitro interactions between tacrolimus, a calcineurin inhibitor, and fluconazole, itraconazole, caspofungin, or anidulafungin were evaluated against Candida auris, C. albicans, C. parapsilosis, and C. glabrata (each five strains). Tacrolimus-itraconazole, tacrolimus-caspofungin, and tacrolimus-fluconazole combinations resulted in synergistic interactions against 95%, 90%, and 60% of Candida isolates, respectively. However, tacrolimus-anidulafungin resulted in only a 35% synergistic effect. A combination of tacrolimus and itraconazole was most potent with synergy against 100% of C. auris, C. parapsilosis, and C. glabrata isolates. Of note, no antagonistic interaction was found.
Topics: Animals; Antifungal Agents; Candida; Tacrolimus; Fluconazole; Candida auris; Caspofungin; Anidulafungin; Itraconazole; Echinocandins; Candida glabrata; Candida parapsilosis; Microbial Sensitivity Tests
PubMed: 37437917
DOI: 10.1093/mmy/myad069 -
Journal of Fungi (Basel, Switzerland) Jun 2023is an emerging fungal pathogen responsible for hospital outbreaks of invasive candidiasis associated with high mortality. The treatment of these mycoses is a clinical...
is an emerging fungal pathogen responsible for hospital outbreaks of invasive candidiasis associated with high mortality. The treatment of these mycoses is a clinical challenge due to the high resistance levels of this species to current antifungal drugs, and alternative therapeutic strategies are needed. In this study, we evaluated the in vitro and in vivo activities of combinations of citral with anidulafungin, amphotericin B or fluconazole against 19 isolates. The antifungal effect of citral was in most cases similar to the effect of the antifungal drugs in monotherapy. The best combination results were obtained with anidulafungin, with synergistic and additive interactions against 7 and 11 of the 19 isolates, respectively. The combination of 0.06 μg/mL anidulafungin and 64 μg/mL citral showed the best results, with a survival rate of 63.2% in infected with UPV 17-279. The combination of fluconazole with citral reduced the MIC of fluconazole from > 64 to 1-4 μg/mL against 12 isolates, and a combination of 2 μg/mL fluconazole and 64 μg/mL citral was also effective in reducing mortality in . Amphotericin B combined with citral, although effective in vitro, did not improve the activity of each compound in vivo.
PubMed: 37367584
DOI: 10.3390/jof9060648 -
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 -
Bioprocess and Biosystems Engineering Jul 2023Echinocandin B (ECB) is the key precursor compound of the antifungal drug Anidulafungin. The effects of the five precursor amino acids on ECB biosynthesis were firstly...
Echinocandin B (ECB) is the key precursor compound of the antifungal drug Anidulafungin. The effects of the five precursor amino acids on ECB biosynthesis were firstly investigated. It showed that although L-threonine was a main compound of the hexapeptide scaffold of ECB, exogenous addition of L-threonine had no significant effect on the increase of ECB fermentation titer. Meanwhile, the ECB fermentation titer with methyl oleate showed two times higher than that of the other carbon sources. Transcription level analysis of the key genes for ECB biosynthesis indicated that the gene an655543 related to L-threonine biosynthesis showed higher value during the fermentation process, therefore, the exogenous addition of L-threonine had no obvious affection. Furthermore, it indicated that the transcription level of gene ecdA might be the main restriction factor for the ECB biosynthesis. The study provided the research foundation for the modification of the ECB producing strains in the following work.
Topics: Fermentation; Echinocandins; Antifungal Agents
PubMed: 37253987
DOI: 10.1007/s00449-023-02883-4