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.

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.

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.

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.

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.

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.

Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.

With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.

Recurrent Vulvovaginal Candidosis and Cluster Analysis of Clinical Signs and Symptoms: A Laboratory-Based Investigation.

Recurrent vulvovaginal candidosis (RVVC) represents a major health problem that significantly affects a patient's quality of life (QoL). This infection presents with a plethora of clinical manifestation, and this is the first study that carries out a cluster analysis of these signs and symptoms (SS). The goals are to evaluate the distribution of species causing RVVC, their in-vitro susceptibility to antifungals, and the patient's QoL. Additionally, the clinical characteristics are analyzed using cluster analysis. Prospective analysis of data was performed for women diagnosed with RVVC in the period from January 2016 to December 2019 based on the analysis of data from a single-center's records. The standard mycological methods and antifungal susceptibility testing were done. Clinical characteristics and QoL were examined by appropriate questions. The cluster analysis was used to identify clusters of SS. A total of 320 women were diagnosed. The dominant species was Candida (C.) albicans. Non-albicans Candida (NAC) yeast was found in 24.4%, and the most common was C. glabrata. Interestingly, Saccharomyces (S.) cerevisiae was detected in 2%. All of the isolated species, except C. parapsilosis and C. kefyr, demonstrated reduced susceptibility to antifungals. We confirmed the emergence of the NAC species and S. cerevisiae with reduced susceptibility to antifungals. Cluster analysis represented by a dendrogram revealed three SS clusters: irritation, uncommon, and discharge, but further studies are needed to examine the relationship between clusters, Candida strains, and outcomes.

Diagnosis of Pneumocystis jirovecii Pneumonia in Pediatric Patients in Serbia, Greece, and Romania. Current Status and Challenges for Collaboration.

Pneumocystis jirovecii can cause fatal Pneumocystis pneumonia (PcP). Many children have been exposed to the fungus and are colonized in early age, while some individuals at high risk for fungal infections may develop PcP, a disease that is difficult to diagnose. Insufficient laboratory availability, lack of knowledge, and local epidemiology gaps make the problem more serious. Traditionally, the diagnosis is based on microscopic visualization of Pneumocystis in respiratory specimens. The molecular diagnosis is important but not widely used. The aim of this study was to collect initial indicative data from Serbia, Greece, and Romania concerning pediatric patients with suspected PcP in order to: find the key underlying diseases, determine current clinical and laboratory practices, and try to propose an integrative future molecular perspective based on regional collaboration. Data were collected by the search of literature and the use of an online questionnaire, filled by relevant scientists specialized in the field. All three countries presented similar clinical practices in terms of PcP prophylaxis and clinical suspicion. In Serbia and Greece the hematology/oncology diseases are the main risks, while in Romania HIV infection is an additional risk. Molecular diagnosis is available only in Greece. PcP seems to be under-diagnosed and regional collaboration in the field of laboratory diagnosis with an emphasis on molecular approaches may help to cover the gaps and improve the practices.

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.

Subgingival areas as potential reservoirs of different Candida spp in type 2 diabetes patients and healthy subjects.

OBJECTIVES: The aim of this cross-sectional observational study was to compare the prevalence of different oral Candida spp. in patients with Type 2 Diabetes and chronic periodontitis in two oral sites: dorsal surface of the tongue and subgingival area. In order to determine subgingival areas as potential reservoirs of yeasts, this study aimed to find differences in the yeasts' detection between the dorsum of the tongue, as the oral site most commonly inhabited with microorganisms, and subgingival samples. Additionally, potential predictors for the yeasts prevalence were determined. MATERIAL AND METHODS: Subjects (N = 146) were divided into four groups: group A- healthy individuals without periodontitis, group B- healthy individuals with chronic periodontitis, group C- Type 2 Diabetes patients with good glycoregulation and Chronic periodontitis and group D- Type 2 Diabetes patients with poor glycoregulation and Chronic periodontitis. Samples were obtained from the tongue by swabbing. Subgingival plaque samples were taken by paper points and periodontal curette. Isolation and identification of different Candida spp. was done using ChromAgar medium. In addition, germ-tube production and carbohydrate assimilation tests were performed. RESULTS: The prevalence of Candida spp. was higher in diabetics with poor glycoregulation. The most frequently isolated species was Candida albicans followed by Candida glabrata and Candida tropicalis. In 15.6% of cases, Candida spp. was present in the subgingival area while absent on the tongue. Multivariate regression model showed that HbA1c was Candida spp. predictor for both locations. CONCLUSIONS: Our results confirmed that there are Candida spp. carriers among subjects with clinically healthy oral mucosa. Also, this study identified subgingival areas as potential reservoirs of these pathogenic species. Glycoregulation has been recognized as a positive predictor factor of Candida spp.

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.

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.

Development and validation of mathematical models for testing antifungal activity of different essential oils against Candida species.

OBJECTIVE: The upward trend in using plant materials introduced essential oils (EOs) as a valuable, novel, bioactive antifungal agent and as an alternative to standard treatment protocol of denture stomatitis caused by Candida species. Therefore, the aim was to evaluate the antifungal activity of different EOs and to present the response surface methodology (RSM) and artificial neural network (ANN) as possible tools for optimizing and predicting EOs antifungal activity. METHODS: Minimum inhibitory concentration (MIC) and Minimum fungicidal concentration (MFC) of the EOs against 3 species Candida spp. (C. albicans, C. tropicalis, C. glabrata) isolated in patients with DS were determined, together with optimization and prediction based on non-terpene and terpene content in EOs, using two mathematical models RSM and ANN-GA. RESULTS: The highest concentrations of EO M. alternifolia inhibited (1.6-2.8 µg/ml) and fungicided (3.5-6.0 µg/ml) all three investigated Candida spp. while the lowest concentrations of EO C. limon inhibited (0.2 - 0.5 µg/ml) and fungicided (0.6-1.1 µg/ml). Among the three types of Candida, C. glabrata was the most sensitive. The RSM modelling proved that MICs and MFCs statistically depend on non-terpene and terpene content in different EOs (<0.0001). Both models showed that a citrus oil (EO C. limon) with 89% content of terpenes and limonene as major constituent was more antifungal efficient. CONCLUSIONS: The investigated EOs showed a broad spectrum of anticandidal activity, also confirmed using the RSM and ANN-GA models. Since EOs can be cytotoxic in higher concentrations, models may be used for qualitative and quantitative dosage predictions of the antifungal activity of EOs.

The severity of denture stomatitis as related to risk factors and different Candida spp.

OBJECTIVES: 1) To select patients with Candida-related denture stomatitis (DS) and to study possible risk factors associated with DS, 2) to evaluate the severity of DS according to Newton's classification, and 3) to investigate the association between the presence of non-albicans Candida spp. (NAC) or mixed Candida spp. and the severity of DS. STUDY DESIGN: Eighty-two patients with Candida-positive DS have undergone 1) filling in the interview questionnaire, 2) clinical examination, and 3) microbiologic examination. RESULTS: A total of 113 Candida spp. isolates were obtained from Candida-positive DS patients: C. albicans (as a single species) in 47/82 (57%) patients (study group A [SG_A]) and NAC/mixed Candida spp. in 35/82 (43%) patients (SG_B). Univariate logistic regression analysis showed that older age, longer age of the mandibular denture, and ex-smoker status were associated with SG_A. A multivariate model revealed no significant predictor of DS severity. Patients from SG_A were 3 times as likely to have DS type I, while patients from SG_B were 4.9 times as likely to have DS type III. CONCLUSIONS: Our results show the association between type III of DS (by Newton's classification) and the presence of NAC or mixed Candida spp. in denture wearers.

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

[This corrects the article DOI: 10.3389/fmicb.2018.00516.].

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.

Importance of Resolving Fungal Nomenclature: the Case of Multiple Pathogenic Species in the Cryptococcus Genus.

Cryptococcosis is a major fungal disease caused by members of the Cryptococcus gattii and Cryptococcus neoformans species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made. The two varieties within C. neoformans were raised to species level, and the same was done for five genotypes within C. gattii. In a recent perspective (K. J. Kwon-Chung et al., mSphere 2:e00357-16, 2017, https://doi.org/10.1128/mSphere.00357-16), it was argued that this taxonomic proposal was premature and without consensus in the community. Although the authors of the perspective recognized the existence of genetic diversity, they preferred the use of the informal nomenclature "C. neoformans species complex" and "C. gattii species complex." Here we highlight the advantage of recognizing these seven species, as ignoring these species will impede deciphering further biologically and clinically relevant differences between them, which may in turn delay future clinical advances.

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.