Predictors for Prolonged Hospital Stay Solely to Complete Intravenous Antifungal Treatment in Patients with Candidemia: Results from the ECMM Candida III Multinational European Observational Cohort Study.

BACKGROUND: To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). METHODS: Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. FINDINGS: Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 - 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 - 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 - 0.45; p < 0.03). INTERPRETATION: Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis.

Species distribution and epidemiological characteristics of superficial fungal infections in Southeastern Serbia.

BACKGROUND: Superficial fungal infections (SFI), one of the most prevalent diseases in the world, are infections of keratin-rich structures of human body mostly caused by dermatophytes and yeasts. OBJECTIVES: The goal of this study was to determine the possible changes in the epidemiology of SFI on the territory of Southeastern Serbia and to investigate epidemiological characteristics and the influence of SFI on the patient's quality of life. METHODS: From 2012 to the end of 2017, samples of 1643 patients (568 males and 1075 females, mean age 40.32 ± 22.44 years) with suspected SFI from Southeastern Serbia were examined using the standard mycological methods. The questionnaires were used to investigate epidemiological characteristics. RESULTS: Superficial fungal infections were diagnosed in 20.5% (n = 336) of patients. In the group of dermatophytes, the most prevalent was Microsporum canis (63.9%, n = 76) followed by Trichophyton mentagrophytes (21.8%, n = 26). Non-albicans Candida species were dominant aetiological agents of superficial candidosis (62.3%). BMI ≥25 kg/m2 (P = 0.019) was determined as an independent risk factor for SFI. There was a statistically significant difference in the EQVAS score between the groups of patients and the control group (P < 0.001). CONCLUSIONS: Results of conducted study indicate that SFI prevalence has not changed in the previous period. However, increase of Candida-SFI prevalence, especially Candida onychomycosis, was established.

ECMM CandiReg-A ready to use platform for outbreaks and epidemiological studies.

BACKGROUND: Recent outbreaks of Candida auris further exemplify that invasive Candida infections are a substantial threat to patients and healthcare systems. Even short treatment delays are associated with higher mortality rates. Epidemiological shifts towards more resistant Candida spp. require careful surveillance. OBJECTIVES: Triggered by the emergence of C auris and by increasing antifungal resistance rates the European Confederation of Medical Mycology developed an international Candida Registry (FungiScope™ CandiReg) to allow contemporary multinational surveillance. METHODS: CandiReg serves as platform for international cooperation to enhance research regarding invasive Candida infections. CandiReg uses the General Data Protection Regulation compliant data platform ClinicalSurveys.net that holds the electronic case report forms (eCRF). Data entry is supported via an interactive macro created by the software that can be accessed via any Internet browser. RESULTS: CandiReg provides an eCRF for invasive Candida infections that can be used for a variety of studies from cohort studies on attributable mortality to evaluations of guideline adherence, offering to the investigators of the 28 ECMM member countries the opportunity to document their cases of invasive Candida infection. CandiReg allows the monitoring of epidemiology of invasive Candida infections, including monitoring of multinational outbreaks. Here, we describe the structure and management of the CandiReg platform. CONCLUSION: CandiReg supports the collection of clinical information and isolates to improve the knowledge on epidemiology and eventually to improve management of invasive Candida infections. CandiReg promotes international collaboration, improving the availability and quality of evidence on invasive Candida infection and contributes to improved patient management.

Laboratory-Based Investigation of Denture Sonication Method in Patients with Candida-Associated Denture Stomatitis.

PURPOSE: Denture stomatitis (DS) is a disease characterized by inflammation and erythema of the oral mucosa areas covered by the denture. Multifactorial etiological factors contribute to DS, but it seems that Candida plays the key role. The aim of the study was to evaluate the denture sonication method to: (i) increase the possibility of diagnosing patients with Candida-associated DS; (ii) detect and identify the mixed Candida spp., and (iii) determine the Candida colony forming units (CFU) and its possible relationship with DS severity, based on Newton's classification. MATERIALS AND METHODS: The cross-sectional study conducted at the Clinic for Dental Prosthetics, Belgrade (Serbia) from June 2013 to December 2014 enrolled edentulous patients with dentures (n = 250). Patients without DS (n = 20) were the control group (CG). The patients' data were collected, and patients with DS (study group/SG) were selected and divided into SG Candida+ and SG Candida-. Based on severity of DS, the SG patients were classified in 3 groups (Newton's classification). Four sampling methods were applied to detect patients with Candida-associated DS: mucosa swab, denture swab, oral rinse, and denture sonication method. The sensitivity and specificity of denture sonication method were shown using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: In 97 (38.8%), out of 250 clinically examined patients, DS was diagnosed. In 82 (84.5%), out of 97 mycologically examined patients, Candida-associated DS was detected when denture sonication method was applied. Additionally, using the denture sonication method we observed: (i) the largest number of Candida positive patients compared to other sampling methods (p < 0.0001); (ii) the highest number of Candida CFU/ml (105 ), and (iii) the possibility to detect mixed Candida cultures. The largest number of patients with Candida-associated DS showed type II (60%) DS, followed by type I (21%), and type III (19%) DS. CONCLUSION: The denture sonication method is easy, accurate, and sensitive, and increases the possibility of diagnosing patients with Candida-associated DS. Additionally, yeast quantification, mixed Candida spp., and non-albicans Candida were detectable when cultivation on Candida CHROMagar was performed. It was not possible using conventional methods, such as swab or oral rinse.

Candida bloodstream infections in Serbia: First multicentre report of a national prospective observational survey in intensive care units.

Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective 12-months (2014-2015) hospital- and laboratory-based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among nine centres (265 beds; 10 820 patient admissions), four neonatal/paediatric (NICU/PICUs) and five adult centres (ICUs) participated, representing 89 beds and 3446 patient admissions, 166 beds and 7347 patient admissions respectively. The NRMML received 43 isolates, 17 from NICU/PICUs and 26 from adult ICUs. C. albicans dominated highly in NICU/PICUs (~71%), whereas C. albicans and C. parapsilosis were equally distributed within adults (46%, each), both accounting for ~90% of received isolates. The resistance to itraconazole and flucytosine were 25% and 2.4% respectively. In addition, the 2 C. albicans were azole cross-resistant (4.6%). The overall incidence of CandidaBSI was ~3.97 cases/1000 patient admissions (4.93 in NICU/PICU and 3.53 in adult ICU). The 30-day mortality was ~37%, most associated with C. tropicalis and C. glabrataBSI. Data from this national survey may contribute to improving the Balkan and Mediterranean region epidemiology of CandidaBSI within ICUs.

Improving outcome of fungal diseases - Guiding experts and patients towards excellence.

Invasive fungal infections are on the rise and during recent years understanding the epidemiology of fungal infections improved. Over 1 billion people are affected and 25 million patients are at imminent risk of severe organ damage or death due to fungal infection. The European Confederation of Medical Mycology (ECMM), founded in 1993, is the roof organisation of 23 National Medical Mycology Societies in Europe. ECMM fights fungal infections at various levels, by creating and distributing scientific knowledge and promoting scientific exchange. In response to the increasing prevalence and management complexity of invasive fungal infections, ECMM recently launched three additional initiatives (https://www.ecmm.info/). (i) ECMM together with other European infectious diseases societies created a comprehensive set of European guidelines for the diagnostic and therapeutic management of invasive fungal infections. (ii) ECMM founded the ECMM Academy awarding fellow status (FECMM) to outstanding researchers who advanced medical mycology. The academy aims at strengthening networking activities between these researchers. (iii) Centres throughout the world can apply for ECMM Excellence Center Status. Following such application on site auditing of up to three levels of mycological work (clinical, microbiological, epidemiological/clinical trials) evaluates the excellence of a centre along predefined criteria. All three initiatives share a common ambition; they aim at improving outcome of fungal diseases through guiding experts and patients towards excellence. Acknowledging fungal infections as a global problem, all three initiatives explicitly reach out beyond European borders.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition.

BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.

The prevalence of Candida onychomycosis in Southeastern Serbia from 2011 to 2015.

Despite the increasing of onychomycosis caused by Candida spp., in referent literature, there is still data insufficiency about this nail infection. The objectives of this retrospective study were to determine epidemiological characteristics of Candida onychomycosis, the antifungal susceptibility of isolated species in vitro, and to compare the results of antifungal susceptibility testing with conducted treatment in period from 2011 to the end of March 2015. Out of 761 patients who were underwent clinical and mycological examinations, 137 had Candida species isolated from nails. The dominant species was Candida albicans (C. albicans) (36.59%) followed by C. parapsilosis (23.78%), C. krusei (9.76%), and C. guilliermondii (6.71%). Antifungal susceptibility in vitro testing showed good susceptibility to antimycotics, except C. krusei, which was resistance to fluconazole (FCZ) and isolates of C. tropicalis and C. glabrata which were dose dependent to itraconazole (ITZ) and fluconazole. Evaluation of medical histories determined that combined therapy, which included pulsed systemic regimen of ITZ with topical application of clotrimazole, had better clinical outcomes regarding the proscribed only topical application of clotrimazole. Multidisciplinary approach of dermatologists and mycologists is required in solving the problem of onychomycosis, which is the dominant nail disease.

Presence, species distribution, and density of Malassezia yeast in patients with seborrhoeic dermatitis - a community-based case-control study and review of literature.

Malassezia yeast belongs to the normal cutaneous flora and under certain conditions it causes seborrhoeic dermatitis (SD). There is no culture-based study about the presence and density of the Malassezia in SD patients in Serbia. Aim was to show the presence, species distribution and density of Malassezia in patients with SD on lesional skin (LS) and non-lesional skin (NLS) and healthy controls (HC) and to compare data between Serbia and other countries. The study included 70 HC and 60 patients with SD in the study group (SG). Isolation, identification and examination of density of Malassezia colony-forming units from LS and NLS were performed. Malassezia was found more frequently in the SG than in HC, 90% and 60%, respectively (P < 0.01). The most frequent isolates in SG on LS were M. slooffiae (26%), followed by M. globosa (17%) and M. sympodialis (17%). The yeast density was much higher on LS of SG than on NLS of SG or in the HC group (P < 0.05). Higher density of Malassezia was shown on LS of SG than on NLS of SG and HC. M. slooffiae is the most prevalent species in SD patients in Serbia. This study demonstrated a positive relationship between severity of SD and presence of Malassezia spp.

Alternaria-Associated Fungus Ball of Orbit Nose and Paranasal Sinuses: Case Report of a Rare Clinical Entity.

Alternaria-associated fungus ball of maxillar, ethmoidal paranasal sinuses, nasal cavity and orbit with bone erosion is extremely rare. Till recently, only two cases of this infection in immune competitive patients have been reported. We are herein describing the case of immune-competent woman who suffered of nasal congestion for 10 years. Patient was treated for tumor-like lesion in right maxillar sinus, where propagation in right nose cavity, right ethmoidal cells and right orbita was present. The organism that was seen in surgical removal of fungal debris by histological study, in using mycological testing, was proven as Alternaria alternata. Combination of surgical intervention and treatment with itraconazole eradicated fungal infection, and the disease was not relapsed in follow-up period of 2 years.

Seroreactivity to Dirofilaria antigens in people from different areas of Serbia.

BACKGROUND: The Northern part of Serbia is hyperendemic-endemic for canine dirofilarioses. Considering this fact, many human dirofilarial infections could be expected, however only about 30 cases in Serbia have been described until today. Aims of this survey were to assess the people reactivity to the antigens of D. repens and D. immitis and to identify risk factors for the contact exposure. METHODS: Investigation included sera taken from 297 people (179 women and 118 men) living in different areas of Serbia (Pancevo, Novi Sad, Zajecar, Leskovac, Vranje, Nis, Pirot). Sera were analysed by means of two indirect enzyme-linked immunosorbent (ELISA) home-designed that use as antigens adult somatic/metabolic polyproteins of D. repens (DR) and D. immitis (DI), respectively. The results were elaborated using the statistical method of descriptive and quantitative analysis. RESULTS: Significant differences by area in the reactivity of human sera to dirofilarial antigens were not observed (p = 0.056). A high seroreactivity was demonstrated in people from the towns of northern Serbia (Pancevo = 27,1%; Novi Sad = 16,3%), as well as in people from Zajecar (eastern Serbia = 15,8%) and Vranje (southern Serbia = 15,1%). No differences were evidenced between people reactivity to polyproteins of the two dirofilarial species, nor differences related to the gender of examinees. Factor risks evidenced were: i) place of residence; ii) spending work time outdoors during the mosquito season; iii) spending time outdoors and nearby rivers, lakes, swamps or canals; unespectedly, iv) cat owning. CONCLUSION: The findings emerging from this investigation indicate that clinicians and public health authorities should pay greater attention to this zoonosis. Continuing education and training of physicians will greatly contribute to the knowledge of the actual impact of filarial worms on animal and public health, and allow for the planning of suitable measures to prevent the infections.

In vitro protease inhibition and cytotoxicity of Aspergillus fumigatus biomolecules secreted under long-term aerated conditions.

The fatality rate of invasive aspergillosis (IA) is still very high, especially in prolonged and untreated pulmonary cases. Aspergillus fumigatus is the main causative agent of IA and investigation of its metabolites could provide valuable insight into virulence factor(s) associated with this organism. We evaluated the A. fumigatus culture filtrate (CF) products generated during short- and long-term aerated and non-aerated conditions and tested for (i) inhibition of cysteine or serine proteases and (ii) cytotoxicity. In addition, the mathematical model was determined using response surface methodology (RSM) to estimate the influence of different fermentation conditions on A. fumigatus CF characteristics, predict enzyme inhibition and make possible correlations with in vivo conditions. Biosynthesis of A. fumigatus low molecular weight proteinaceous products (from 6.4 to 15.4 kDa) was observed after 6 days of growth under aerated and alkaline conditions. Also, only these CFs showed significant reduction in cell lines survival (Caco-2 and WISH 35.6% and 54.6%, respectively). Obtained results provide solid starting point for further studies that would include: (i) detailed chemical characterization of A. fumigatus CF, (ii) activity relationships and in vivo correlation with pathogenicity of prolonged pulmonary IA and (iii) possible use of biomolecules as diagnostic or therapeutic markers.

Molecular epidemiology and antifungal susceptibility of Serbian Cryptococcus neoformans isolates.

Molecular typing and antifungal susceptibility testing of 34 clinical Serbian Cryptococcus neoformans isolates from 25 patients was retrospectively performed. Amplified fragment length polymorphism (AFLP) fingerprinting was used for genotyping, whereas a novel real-time PCR was used to determine the mating- and serotype. The antifungals amphotericin B, 5-fluorocytosine, fluconazole, voriconazole, itraconazole and posaconazole were used to determine the antifungal susceptibility profiles. The majority of isolates belonged to genotype AFLP1/VNI (n = 20; 58.8%), followed by AFLP2/VNIV (n = 10; 29.4%), AFLP3/VNIII (n = 3; 8.8%) and AFLP1B/VNII (n = 1; 2.9%). All AFLP1/VNI isolates were mating-serotype αA, the sole AFLP1B/VNII isolate was found to be aA, whereas AFLP2/VNIV harboured serotype D isolates with either the a (n = 2; 5.9%) or α (n = 8; 23.5%) mating-type allele. The isolates (n = 3; 8.8%) that were found to be genotype AFLP3/VNIII had the hybrid mating- and serotype combination aA-αD. In vitro antifungal susceptibility testing showed that all isolates were susceptible to amphotericin B, voriconazole and posaconazole. Low resistance level was observed for fluconazole (n = 1; 2.9%) and 5-fluorocytosine. (n = 2; 5.8%). A large percentage of isolates was found to be susceptible dose dependent to itraconazole (n = 16; 47.1%). AFLP1/VNI was the most common genotype among clinical C. neoformans isolates from immunocompromised patients in Serbia. C. neoformans from HIV-negative patients were significantly less susceptible to 5-fluorocytosine (P < 0.01). Correlation between genotypes and antifungal susceptibility was not observed.

A laboratory-based study on patients with Parkinson's disease and seborrheic dermatitis: the presence and density of Malassezia yeasts, their different species and enzymes production.

BACKGROUND: Seborrheic dermatitis (SD) and Parkinson's disease (PD) are frequently associated conditions. Aims of this study were: to determine severity of SD, presence of different species and density of Malassezia yeasts; to assess yeast lipases and phosphatases production in vitro and to compare these results between SD patients with and without PD. METHODS: This case-control prospective study was conducted at the Dermatology and Neurology Units, Clinical Centre of Serbia and at the National Medical Mycology Reference Laboratory, University of Belgrade Medical School, Serbia. A total of 90 patients and 70 healthy controls (HC) were investigated: 60 patients with SD (SDN) and 30 patients with SD and PD (SDP). Culture-based mycological examination was carried out on lesional skin (LS) and non-lesional skin (NLS). A yeasts density was determined by counting the Malassezia colony forming units per tape (CFU/tape). Enzymes production by isolated Malassezia was investigated. RESULTS: The most patients with SD were male (76.7%; SDP and 63.3%; SDN) and the intensity of SD was dominantly severe or moderate (76.7%; SDP and 75%; SDN). The presence of Malasseziа was high on LS in both groups (87.3%; SDP and 86.7%; SDN) (p=0.667).The highest yeasts density (mean CFU/tape=67.8) was detected on LS in 53% of SDP group and in 21.7% of SDN group (mean CFU/tape=31.9) (p < 0.01). The presence of negative cultures was lower in SDP group (13.3%) in comparison to HC and SDN groups (37% and 31.7%, respectively). Malassezia density on NLS in SDP group (mean CFU/tape=44.3) was significantly higher in comparison to SDN and HC (p=0.018). M. globosa was the most abundant species identified amongst isolates from the SDP group (42.3%) and exhibited high production of phosphatase and lipase in vitro. CONCLUSION: From this laboratory-based study a positive correlation between SD, PD, M. globosa incidence, high yeast density and high phosphatase and lipase activity was established. Our data lead to conclusion that local skin performance of PD patient's characterized with increased sebum excretion ratio play a role in SD by stimulation of yeasts replication and enzyme production.

A Systematic Review of Denture Stomatitis: Predisposing Factors, Clinical Features, Etiology, and Global Candida spp. Distribution.

Denture stomatitis (DS) is a very common disease in wearers of removable complete and partial dentures with a worldwide prevalence in the range of 20-67%. Both industrially developed and impoverished nations are affected by the illness. DS is often associated with ill-fitting dentures or a fungal infection with Candida spp. Candida is normally found in the oral cavity microbiota, but it can be harmful to the health of elderly people with underlying diseases. Therefore, the purpose of the present study is to offer the most recent information about the epidemiology, etiology, and global distribution of Candida species associated with DS through a systematic review. Several databases, including Medline, Web of Science, and Scopus, were used to conduct an extensive search of the literature published in the previous 20 years. The selection of studies was performed by two authors. The extracted data were as follows: author, year of publication, country, sample, frequency of DS, method of diagnosing stomatitis, species of Candida, risk factors, and etiology of the disease. The JBI Critical appraisal tools were used to assess the quality of the studies. Eventually, twenty-eight studies were included in the systematic review. Twenty-one studies investigated DS, while seven studies examined Candida colonization in patients using removable dentures. The results show that the main causes of DS include the type of dentures, continuous wearing of dentures, and the formation of a Candida biofilm, which is facilitated by poor dental hygiene. Additionally, previous studies have pinpointed the significance of the salivary flow, saliva composition, and salivary pH. The findings of the current review indicate that it is crucial to monitor denture wearers for the appearance of DS, especially the patients whose immunity has been impaired due to a systemic condition. Finally, frequent follow-ups should include a clinical examination and microbial swabs of the palatal mucosa and the mucosal surface of the denture.

Etiology, Predisposing Factors, Clinical Features and Diagnostic Procedure of Otomycosis: A Literature Review.

Otomycosis (OM) is a superficial fungal infection of the external auditory canal (EAC) with a worldwide prevalence ranging from 9% to 30%. Commonly, otomycoses are caused by Aspergillus (A.) niger complex and Candida spp. Other causative agents are yeasts of the genera Cryptococcus spp., Rhodotorula spp., Geotrichum candidum, dermatophytes (Trichophyton mentagrophytes), and non-dermatophytes molds (Fusarium spp., Penicillium spp., Mucorales fungi). The widest range of different species causing OM are found in the territories of Iran, India, China, Egypt, Mexico, and Brazil. Fungal infection of the EAC varies from mild to severe forms. It can be acute, subacute, or chronic, and is often unilateral, while the bilateral form is more common in immunocompromised patients. From an epidemiological point of view, tropical and subtropical climates are the most significant risk factor for the development of otomycosis. Other predisposing conditions include clothing habits, EAC hygiene practices, long-term antibiotic therapy, diabetes, and immunodeficiency. Since it is often difficult to distinguish otomycosis from an infection of a different origin, laboratory-based evidence, including standard procedures (microscopy and cultivation), is essential for diagnosis. For the treatment of this superficial fungal infection, there are no official therapeutic guidelines and protocols. However, many antifungals for local application, such as polyene, imidazoles, and allylamines, can be applied, as well as systemic antimycotics (triazoles) in severe forms of infection.

Antifungal Activity and Type of Interaction of Melissa officinalis Essential Oil with Antimycotics against Biofilms of Multidrug-Resistant Candida Isolates from Vulvovaginal Mucosa.

(1) Background: Vulvovaginal candidosis (VVC) is a major therapy issue due to its high resistance rate and virulence factors such as the ability to form biofilms. The possibility of combining commonly used antifungals with natural products might greatly improve therapeutic success. (2) Methods: A total of 49 vulvovaginal isolates, causative agents of recurrent VVC, were tested for their susceptibility to fluconazole, nystatin, and Melissa officinalis essential oil (MOEO). This examination included testing the antibiofilm potential of antifungals and MOEO and the determination of their types of interaction with mature biofilms. (3) Results: Antimicrobial testing showed that 94.4% of the Candida albicans isolates and all the Candida krusei isolates were resistant to fluconazole, while all strains showed resistance to nystatin. The same strains were susceptible to MOEO in 0.156-2.5 mg/mL concentrations. Additionally, the results revealed very limited action of fluconazole, while nystatin and MOEO reduced the amount of biofilm formed by as much as 17.7% and 4.6%, respectively. Testing of the combined effect showed strain-specific synergistic action. Furthermore, the lower concentrations exhibited antagonistic effects even in cases where synergism was detected. (4) Conclusions: This study showed that MOEO had a very good antibiofilm effect. However, combining MOEO with antimycotics demonstrated that the type of action depended on the choice of antifungal drugs as well as the applied concentration.

Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study.

BACKGROUND: The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes. METHODS: In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines. FINDINGS: 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04-1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05-1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals. INTERPRETATION: Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay. FUNDING: Scynexis.

Clinical Presentations, Cluster Analysis and Laboratory-Based Investigation of Aspergillus Otomycosis-A Single Center Experience.

Species of Aspergillus (A.) niger complex and A. flavus complex are predominant molds that are causative agents of otomycoses. The goal of this study was to investigate the clinical presentation, diagnostic procedure, and appearance of relapse in patients with Aspergillus-otomycosis, as well as to determine the biofilm production ability of species isolated in relapse. Thirty patients with laboratory evidenced Aspergillus-otomycosis followed by two check-ups (30 and 60 days after initiation of treatment with antimycotics for local application) were included in the study. For isolation and identification of Aspergillus spp. the standard mycological procedure was applied. Results showed very high sensitivity of microscopy, but 16.7% Aspergillus species required the optimal temperature of 27-28 °C for cultivation. Applied statistical cluster analysis showed a defined specific cluster/group of patients with A. niger complex-otomycosis. Sixty days after diagnosis and treatment initiation, six patients had a relapse, with the same species of Aspergillus genus being the cause. To establish the ability of biofilm production, the modified method described by Pierce and Kvasnicková was performed, and all six species isolated in the relapse episode had the ability to produce biofilm. Official criteria and recommendations are needed due to the possibility of misdiagnosis, which leads to the prolongation and complication of the disease.

Poly(methyl methacrylate) with Oleic Acid as an Efficient Candida albicans Biofilm Repellent.

Poly(methyl methacrylate) (PMMA), widely used in dentistry, is unfortunately a suitable substrate for Candida (C.) albicans colonization and biofilm formation. The key step for biofilm formation is C. albicans ability to transit from yeast to hypha (filamentation). Since oleic acid (OA), a natural compound, prevents filamentation, we modified PMMA with OA aiming the antifungal PMMA_OA materials. Physico-chemical properties of the novel PMMA_OA composites obtained by incorporation of 3%, 6%, 9%, and 12% OA into PMMA were characterized by Fourier-transform infrared spectroscopy and water contact angle measurement. To test antifungal activity, PMMA_OA composites were incubated with C. albicans and the metabolic activity of both biofilm and planktonic cells was measured with a XTT test, 0 and 6 days after composites preparation. The effect of OA on C. albicans morphology was observed after 24 h and 48 h incubation in agar loaded with 0.0125% and 0.4% OA. The results show that increase of OA significantly decreased water contact angle. Metabolic activity of both biofilm and planktonic cells were significantly decreased in the both time points. Therefore, modification of PMMA with OA is a promising strategy to reduce C. albicans biofilm formation on denture.