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Molecular epidemiology and antimicrobial resistance of vaginal Candida glabrata isolates in Namibia.Medical Mycology Jan 2024Candida glabrata is the most common non-albicans Candida species that causes vulvovaginal candidiasis (VVC). Given the intrinsically low susceptibility of C. glabrata to...
Candida glabrata is the most common non-albicans Candida species that causes vulvovaginal candidiasis (VVC). Given the intrinsically low susceptibility of C. glabrata to azole drugs, investigations into C. glabrata prevalence, fungal susceptibility profile, and molecular epidemiology are necessary to optimise the treatment of VVC. This molecular epidemiological study was conducted to determine antifungal drug profile, single nucleotide polymorphisms (SNPs) associated with phenotypic antifungal resistance and epidemic diversity of C. glabrata isolates from women with VVC in Namibia. Candida glabrata isolates were identified using phenotypic and molecular methods. Antifungal susceptibility of strains was determined for fluconazole, itraconazole, amphotericin B, and anidulafungin. Whole genome sequencing was used to determine SNPs in antifungal resistance genes and sequence type (ST) allocation. Among C. glabrata isolates, all (20/20; 100%) exhibited phenotypic resistance to the azole class antifungal drug, (fluconazole), and phenotypic susceptibility to the polyene class (amphotericin B), and the echinocandins (anidulafungin). Non-synonymous SNPs were identified in antifungal resistance genes of all fluconazole-resistant C. glabrata isolates including ERG6 (15%), ERG7 (15%), CgCDR1 (25%), CgPDR1 (60%), SNQ2 (10%), FKS1 (5.0%), FKS2 (5.0%), CgFPS1 (5.0%), and MSH2 (15%). ST15 (n = 8/20, 40%) was predominant. This study provides important insight into phenotypic and genotypic antifungal resistance across C. glabrata isolates from women with VVC in Namibia. In this study, azole resistance is determined by an extensive range of SNPs, while the observed polyene and echinocandin resistance-associated SNPs despite phenotypic susceptibility require further investigation.
Topics: Female; Humans; Antifungal Agents; Candida glabrata; Candidiasis, Vulvovaginal; Fluconazole; Amphotericin B; Anti-Bacterial Agents; Anidulafungin; Molecular Epidemiology; Namibia; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Echinocandins; Azoles; Polyenes; Drug Resistance, Fungal
PubMed: 38308518
DOI: 10.1093/mmy/myae009 -
Mycoses Mar 2024Fluconazole-resistant Candida parapsilosis is a matter of concern.
Fluconazole-resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole-resistance profiles associated with the Y132F ERG11p substitution.
BACKGROUND
Fluconazole-resistant Candida parapsilosis is a matter of concern.
OBJECTIVES
To describe fluconazole-resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole-resistance profile associated with ERG11p substitutions.
PATIENTS/METHODS
We selected fluconazole-resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility.
RESULTS
Of the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city-specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild-type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild-type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole-resistance patterns found were: voriconazole-resistant (74.1%) or voriconazole-intermediate (25.2%), posaconazole-resistant (10%) and isavuconazole non-wild-type (47.5%). Fluconazole-resistant and voriconazole non-wild-type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non-wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L.
CONCLUSIONS
We detected a recent clonal spread of fluconazole-resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city-specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non-susceptible to voriconazole and rarely posaconazole-resistant.
Topics: Humans; Azoles; Fluconazole; Candida parapsilosis; Cities; Voriconazole; Amphotericin B; Anidulafungin; Micafungin; Italy; Hospitals; Genotype; Triazoles; Nitriles; Triterpenes; Glycosides; Pyridines
PubMed: 38438313
DOI: 10.1111/myc.13706 -
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 -
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 -
Medical Mycology May 2024Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these... (Comparative Study)
Comparative Study
Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited, and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor, and outcome. In addition, a candidemia group, including patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to the reference method. A total of 85 patients with fungemia episodes were included: 25 with NCY fungemia and 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole, and amphotericin B were ≤ 2 µg/ml, and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs, and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters, and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species was the problem, particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.
Topics: Humans; Retrospective Studies; Tertiary Care Centers; Antifungal Agents; Male; Female; Middle Aged; Microbial Sensitivity Tests; Aged; Candida; Fungemia; Adult; Candidemia; Yeasts; Aged, 80 and over; Fluconazole; Young Adult
PubMed: 38627248
DOI: 10.1093/mmy/myae037 -
The Medical Letter on Drugs and... Jun 2024
Topics: Humans; Antifungal Agents; Candidiasis, Invasive; Echinocandins
PubMed: 38905526
DOI: 10.58347/tml.2024.1705d -
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 -
Biomaterials Science Feb 2024Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal...
Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC = 3.5 μM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 μM, better than fluconazole (17.2% at 1 μM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.
Topics: Humans; Animals; Mice; Antifungal Agents; Fluconazole; alpha-Fetoproteins; Peptides; Fungi
PubMed: 38193333
DOI: 10.1039/d3bm01845h -
Mycoses Apr 2024Candidaemia is a life-threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing...
BACKGROUND
Candidaemia is a life-threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing with the epidemiologic characteristics of biofilm-related properties is limited.
OBJECTIVE
This study evaluated the clinical characteristics of candidaemia, to assess the biofilm-forming properties of isolates, and to identify the risk factors of mortality.
PATIENTS AND METHODS
A total of 149 candidaemia episodes from the University of Debrecen, Clinical Centre, between January 2020 and December 2023 were investigated retrospectively. The susceptibility of Candida isolates to fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin was evaluated and compared to the susceptibility of 1-day-old biofilms. Multivariate logistic regression analysis was applied to identify the independent predictors of 30-day mortality rate.
RESULTS
The most common Candida species was Candida albicans (41%), followed by C. parapsilosis (20%), C. glabrata (14%), C. tropicalis (13%), rare Candida species (7%), and C. krusei (5%). Sixty-six percent of Candida isolates were biofilm formers and 44% had high metabolic activity. The 30-day mortality rate was 52%, which was higher in ICUs (65%). The logistic regression analysis revealed several factors significantly influencing mortality including ICU admission (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.17-8.04, p = 0.025), fluconazole treatment (OR 4.12, 95% CI 1.62-11.42, p = .004), and pneumonia (OR 0.261, 95% CI 0.1-0.67, p = .006).
CONCLUSIONS
This comprehensive analysis supports the better characterisation of candidaemia in healthcare settings, which ultimately may reduce mortality among patients.
Topics: Humans; Candidemia; Biofilms; Retrospective Studies; Female; Male; Hungary; Antifungal Agents; Candida; Middle Aged; Aged; Microbial Sensitivity Tests; Adult; Risk Factors; Intensive Care Units; Aged, 80 and over; Fluconazole
PubMed: 38650397
DOI: 10.1111/myc.13727