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Journal of Fungi (Basel, Switzerland) Jan 2024is a recently emerged human fungal pathogen that has posed a significant threat to public health. Since its first identification in 2009, this fungus has caused...
is a recently emerged human fungal pathogen that has posed a significant threat to public health. Since its first identification in 2009, this fungus has caused nosocomial infections in over 47 countries across all inhabited continents. As of May 2023, the whole-genome sequences of over 4000 strains have been reported and a diversity of mutations, including in genes known to be associated with drug resistance in other human fungal pathogens, have been described. Among them, 387 strains contained antifungal-susceptibility information for which different methods might be used depending on the drugs and/or investigators. In most reports on so far, the number of strains analyzed was very small, from one to a few dozen, and the statistical significance of the relationships between these genetic variants and their antifungal susceptibilities could not be assessed. In this study, we conducted genome-wide association studies on individual clades based on previously published isolates to investigate the statistical association between genomic variants and susceptibility differences to nine antifungal drugs belonging to four major drug categories: 5-fluorocytosine, amphotericin B, fluconazole, voriconazole, itraconazole, posaconazole, anidulafungin, caspofungin, and micafungin. Due to the small sample sizes for Clades II, V, and VI, this study only assessed Clades I, III, and IV. Our analyses revealed 15 single nucleotide polymorphisms (SNPs) in Clade I (10 in coding and 5 in noncoding regions), 24 SNPs in Clade III (11 in coding and 13 in noncoding regions), and 13 SNPs in clade IV (10 in coding and 3 in noncoding regions) as statistically significantly associated with susceptibility differences to one or more of the nine antifungal drugs. While four SNPs in genes encoding lanosterol 14-α-demethylase ) and the catalytic subunit of 1,3-beta-D-glucan synthase () were shared between clades, including the experimentally confirmed Ser639Phe/Pro missense substitutions in for echinocandin resistance, most of the identified SNPs were clade specific, consistent with their recent independent origins. Interestingly, the majority of the antifungal resistance-associated SNPs were novel, and in genes and intergenic regions that have never been reported before as associated with antifungal resistance. While targeted study is needed to confirm the role of each novel SNP, the diverse mechanisms of drug resistance in revealed here indicate both challenges for infection control and opportunities for the development of novel antifungal drugs against this and other human fungal pathogens.
PubMed: 38276031
DOI: 10.3390/jof10010086 -
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 -
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 -
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 -
Epidemiology and Infection Aug 2023Antifungal susceptibility of species is decreasing. Successful treatment for antifungal-resistant candida infection is challenging and associated with significant... (Observational Study)
Observational Study
Antifungal susceptibility of species is decreasing. Successful treatment for antifungal-resistant candida infection is challenging and associated with significant mortality. We performed a prospective observational study to identify the species and antifungal susceptibilities of invasive isolates of species over a 5-year period at a university hospital in southern Thailand. Between 2017 and 2021, the species distribution was 39.1% , 24.8% , 20.3% complex, 10.5% , and 5.2% miscellaneous spp. Notable observations include elevated minimal inhibitory concentration (MIC) and decrease susceptibility of and to echinocandin and all tested triazoles. A shift of MIC value in the COVID-19 era was seen in and with azoles and echinocandins. Azole resistance increased among isolates, and echinocandin resistance also increased among and isolates. Novel alterations in 1 HS1 and HS2 were detected in both isolates of anidulafungin-resistant As species have become more resistant to azoles and less susceptible to echinocandin development, the need arose to observe the emergence of resistance to both antifungal classes in candida clinical isolates, for a more effective infection control in the hospital.
Topics: Humans; Candida; Fluconazole; Echinocandins; Antifungal Agents; COVID-19; Candidiasis, Invasive; Hospitals, University; Azoles; Disease Outbreaks
PubMed: 37622338
DOI: 10.1017/S0950268823001346 -
European Journal of Clinical... May 2024This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary...
PURPOSE
This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary mycoses.
METHODS
MIC values for antifungal agents were determined against Candida krusei (now Pichia kudriavzevii) ATCC 6258, Candida albicans ATCC 90028, and 18 clinical isolates using the broth microdilution method in RPMI medium, following EUCAST recommendations. MIC assays included testing with and without Curosurf® surfactant at 1 mg/mL for C. krusei ATCC 6258 and all C. krusei isolates. Subsequent Time-kill studies in Sabouraud broth involved testing both C. albicans ATCC 90028 and C. krusei ATCC 6258 strains at concentrations equal their respective MIC values, with and without surfactant, using all four antifungals. CFU/mL were assessed at multiple time points up to 24 h. TKCs with different surfactant concentrations for C. krusei ATCC 6258 and mini-TKCs at various concentrations relative to the MIC of C. krusei isolates and the reference strain were conducted with micafungin, anidulafungin, and caspofungin.
RESULTS
MIC results showed that 1 µg/mL surfactant reduced killing of micafungin and anidulafungin against C. krusei, while caspofungin was unaffected. Amphotericin B's MIC decreased by half. TKCs demonstrated significant effects of surfactant on micafungin and anidulafungin against C. krusei, with complete abolition of anidulafungin's activity against C. albicans.
CONCLUSION
This in-vitro study highlights the concentration-dependent inhibitory effect of surfactant on antifungal activity against C. krusei and, to some extent, C. albicans, necessitating further clinical validation for invasive lung mycoses treatment.
Topics: Antifungal Agents; Microbial Sensitivity Tests; Humans; Pulmonary Surfactants; Candida albicans; Candida; Micafungin; Candidiasis; Amphotericin B; Echinocandins; Caspofungin
PubMed: 38483681
DOI: 10.1007/s10096-024-04799-7 -
Journal of Clinical Laboratory Analysis Oct 2023Viral pneumonia such as COVID-19-associated aspergillosis could increase susceptibility to fungal super-infections in critically ill patients. (Review)
Review
BACKGROUND
Viral pneumonia such as COVID-19-associated aspergillosis could increase susceptibility to fungal super-infections in critically ill patients.
METHODS
Here we report a pediatric case of Aspergillus quadrilineatus cerebral infection in a recently diagnosed COVID-19-positive patient underlying acute lymphocytic leukemia. Morphological, molecular methods, and sequencing were used to identify this emerging species.
RESULTS
Histopathological examination showed a granulomatous necrotic area containing dichotomously branching septate hyphae indicating a presumptive Aspergillus structure. The species-level identity of isolate growing on brain biopsy culture was confirmed by PCR sequencing of the β-tubulin gene as A. quadrilineatus. Using the CLSI M38-A3 broth microdilution methodology, the in vitro antifungal susceptibility testing demonstrated 0.032 μg/mL MIC for posaconazole, caspofungin, and anidulafungin and 8 μg/mL against amphotericin B. A combination of intravenous liposomal amphotericin B and caspofungin therapy for 8 days did not improve the patient's condition. The patient gradually continued to deteriorate and expired.
CONCLUSIONS
This is the first COVID-19-associated cerebral aspergillosis due to A. quadrilineatus in a pediatric patient with acute lymphocytic leukemia. However, comprehensive screening studies are highly recommended to evaluate its frequency and antifungal susceptibility profiles. Before being recommended as first-line therapy in high-risk patients, more antifungal susceptibility data are needed.
Topics: Humans; Child; Antifungal Agents; Caspofungin; COVID-19; Aspergillus; Aspergillosis; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Central Nervous System; Microbial Sensitivity Tests
PubMed: 37798858
DOI: 10.1002/jcla.24971