Estimated burden of serious human fungal diseases in Turkey

Seyedmousavi, Seyedmojtaba/0000-0002-6194-7447; Denning, David/0000-0001-5626-2251; Hedayati, Mohammad T./0000-0001-6415-4648; Ilkit, Macit/0000-0002-1174-4182WOS: 000453770400004PubMed: 30107069The current number of fungal infections occurring each year in Turkey is unknown. We estimated the burden of serious human fungal diseases based on the population at risk, existing epidemiological data from 1920 to 2017 and modelling previously described by the LIFE program (). Among the population of Turkey (80.8 million in 2017), approximately 1 785 811 (2.21%) people are estimated to suffer from a serious fungal infection each year. the model used predicts high prevalences of allergic fungal rhinosinusitis episodes (312 994 cases) (392/100 000), of severe asthma with fungal sensitisation (42 989 cases) (53.20 cases/100 000 adults per year), of allergic bronchopulmonary aspergillosis (32 594 cases) (40.33/100 000), of fungal keratitis (26 671 cases) (33/100 000) and of chronic pulmonary aspergillosis (5890 cases) (7.29/100 000). the estimated annual incidence for invasive aspergillosis is lower (3911 cases) (4.84/100 000 annually). Among about 22.5 million women aged 15-50 years, recurrent vulvovaginal candidiasis is estimated to occur in 1 350 371 (3342/100 000) females. the burden of three superficial fungal infections was also estimated: tinea pedis (1.79 million), tinea capitis (43 900) and onychomycosis (1.73 million). Given that the modelling estimates reported in the current study might be substantially under- or overestimated, formal epidemiological and comprehensive surveillance studies are required to validate or modify these estimates

Time-Kill Kinetics and In Vitro Antifungal Susceptibility of Non-fumigatus Aspergillus Species Isolated from Patients with Ocular Mycoses

Aspergillus species can cause ocular morbidity and blindness, and thus, appropriate antifungal therapy is needed. We investigated the in vitro activity of itraconazole, voriconazole, posaconazole, caspofungin, anidulafungin, and amphotericin B against 14 Aspergillus isolates obtained from patients with ocular mycoses, using the CLSI reference broth microdilution methodology. In addition, time-kill assays were performed, exposing each isolate separately to 1-, 4-, and 16-fold concentrations above the minimum inhibitory concentration (MIC) of each antifungal agent. A sigmoid maximum-effect (Emax) model was used to fit the time-kill curve data. The drug effect was further evaluated by measuring an increase/decrease in the killing rate of the tested isolates. The MICs of amphotericin B, itraconazole, voriconazole, and posaconazole were 0.5–1.0, 1.0, 0.5–1.0, and 0.25 µg/ml for A. brasiliensis, A. niger, and A. tubingensis isolates, respectively, and 2.0–4.0, 0.5, 1.0 for A. flavus, and 0.12–0.25 µg/ml for A. nomius isolates, respectively. A. calidoustus had the highest MIC range for the azoles (4.0–16.0 µg/ml) among all isolates tested. The minimum effective concentrations of caspofungin and anidulafungin were ≤0.03–0.5 µg/ml and ≤0.03 µg/ml for all isolates, respectively. Posaconazole demonstrated maximal killing rates (Emax = 0.63 h−1, r2 = 0.71) against 14 ocular Aspergillus isolates, followed by amphotericin B (Emax = 0.39 h−1, r2 = 0.87), voriconazole (Emax = 0.35 h−1, r2 = 0.098), and itraconazole (Emax = 0.01 h−1, r2 = 0.98). Overall, the antifungal susceptibility of the non-fumigatusAspergillus isolates tested was species and antifungal agent dependent. Analysis of the kinetic growth assays, along with consideration of the killing rates, revealed that posaconazole was the most effective antifungal against all of the isolates

Species Distinction in the Trichophyton rubrum Complex

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Aspergillus fumigatus and aspergillosis: From basics to clinics

The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A. fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A. fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A. fumigatus. This review paper comprehensively discusses the current clinical challenges caused by A. fumigatus and provides insights on how to address them.AA, RGR, and DSP were supported by NIH AI 109025. MH was supported by NIH UL1TR001442. AC was supported by the Fundação para a Ciência e a Tecnologia (FCT) (CEECIND/03628/2017 and PTDC/MED GEN/28778/2017). Additional support was provided by FCT (UIDB/50026/2020 and UIDP/50026/2020), the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023), the European Union's Horizon 2020 Research and Innovation programme under grant agreement no. 847507, and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HP17/52190003. DJA was supported by CF Trust Strategic Research Centre TrIFIC (SRC015), Wellcome Trust Collaborative Award 219551/Z/19/Z and the NIHR Centre for Antimicrobial Optimisation.S

Candidemia among iranian patients with severe COVID-19 admitted to ICUs

As a novel risk factor, COVID-19 has led to an increase in the incidence of candidemia and an elevated mortality rate. Despite being of clinical importance, there is a lack of data regarding COVID-19-associated candidemia (CAC) among Iranian patients. Therefore, in this retrospective study, we assessed CAC epidemiology in the intensive care units (ICUs) of two COVID-19 centers in Mashhad, Iran, from early November 2020 to late January 2021. Yeast isolates from patients� blood were identified by 21-plex polymerase chain reaction (PCR) and sequencing, then subjected to antifungal susceptibility testing according to the CLSI M27-A3 protocol. Among 1988 patients with COVID-19 admitted to ICUs, seven had fungemia (7/1988; 0.03), among whom six had CAC. The mortality of the limited CAC cases was high and greatly exceeded that of patients with COVID-19 but without candidemia (100 (6/6) vs. 22.7 (452/1988)). In total, nine yeast isolates were collected from patients with fungemia: five Candida albicans, three C. glabrata, and one Rhodotorula mucilaginosa. Half of the patients infected with C. albicans (2/4) were refractory to both azoles and echinocandins. The high mortality of patients with CAC, despite antifungal therapy, reflects the severity of the disease in these patients and underscores the importance of rapid diagnosis and timely initiation of antifungal treatment. © 2021 by the authors

A High Rate of Recurrent Vulvovaginal Candidiasis and Therapeutic Failure of Azole Derivatives Among Iranian Women

Recurrent vulvovaginal candidiasis (RVVC) is one of the most prevalent fungal infections in humans, especially in developing countries; however, it is underestimated and regarded as an easy-to-treat condition. RVVC may be caused by dysbiosis of the microbiome and other host-, pathogen-, and antifungal drug-related factors. Although multiple studies on host-related factors affecting the outcome have been conducted, such studies on Candida-derived factors and their association with RVVC are lacking. Thus, fluconazole-tolerant (FLZT) isolates may cause fluconazole therapeutic failure (FTF), but this concept has not been assessed in the context of Candida-associated vaginitis. Iran is among the countries with the highest burden of RVVC; however, comprehensive studies detailing the clinical and microbiological features of this complication are scarce. Therefore, we conducted a 1-year prospective study with the aim to determine the RVVC burden among women referred to a gynecology hospital in Tehran, the association of the previous exposure to clotrimazole and fluconazole with the emergence of FLZT and fluconazole-resistant (FLZR) Candida isolates, and the relevance of these phenotypes to FTF. The results indicated that about 53 of the patients (43/81) experienced RVVC. Candida albicans and C. glabrata constituted approximately 90 of the yeast isolates (72 patients). Except for one FLZT C. tropicalis isolate, FLZR and FLZT phenotypes were detected exclusively in patients with RVVC; among them, 27.9 (12/43) harbored FLZR strains. C. albicans constituted 81.2 of FLZR (13/16) and 100 of the FLZT (13/13) isolates, respectively, and both phenotypes were likely responsible for FTF, which was also observed among patients with RVVC infected with fluconazole-susceptible isolates. Thus, FTF could be due to host-, drug-, and pathogen-related characteristics. Our study indicates that FLZT and FLZR isolates may arise following the exposure to over-the-counter (OTC) topical azole (clotrimazole) and that both phenotypes can cause FTF. Therefore, the widespread use of OTC azoles can influence fluconazole therapeutic success, highlighting the necessity of controlling the use of weak topical antifungals among Iranian women. © Copyright © 2021 Arastehfar, Kargar, Mohammadi, Roudbary, Ghods, Haghighi, Daneshnia, Tavakoli, Jafarzadeh, Hedayati, Wang, Fang, Carvalho, Ilkit, Perlin and Lass-Flörl