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[This corrects the article DOI: 10.1093/ofid/ofab250.].

[This corrects the article DOI: 10.1093/ofid/ofab250.].

Candida auris has globally emerged as a multidrug-resistant fungus linked to healthcare-associated outbreaks. There is still limited evidence on its virulence, pathogenicity determinants, and complex host-pathogen interactions.This study analyzes the in vivo fungal behavior, immune response, and host-pathogen interactions upon C. auris infection compared to C. albicans and C. parapsilosis in G. mellonella. This was performed by immunolabelling fungal structures and larval plasmatocytes and using a quantitative approach incorporating bioinformatic morphometric techniques into the study of microbial pathogenesis.C. auris presents a remarkably higher immunogenic activity than expected at its moderate degree of tissue invasion. It induces a greater inflammatory response than C. albicans and C. parapsilosis at the expense of plasmatocyte nodule formation, especially in non-aggregative strains. It specifically invades the larval respiratory system, in a pattern not previously observed in other Candida species, and presents inter-phenotypic tissue tropism differences. C. auris filaments in vivo less frequently than C. albicans or C. parapsilosis mostly through pseudohyphal growth. Filamentation might not be a major pathogenic determinant in C. auris, as less virulent aggregative phenotypes form pseudohyphae to a greater extent. C. auris has important both interspecific and intraspecific virulence and phenotype heterogeneity, with aggregative phenotypes of C. auris sharing characteristics with low pathogenic species such as C. parapsilosis. Our work suggests that C. auris owns an important morphogenetic plasticity that distinguishes it from other yeasts of the genus. Routine phenotypic identification of aggregative or non-aggregative phenotypes should be performed in the clinical setting as it may impact patient management.

GEMICOMED (SEIMC) and the Spanish CANDI-Bundle Group., [Background] Candidaemia is a leading cause of bloodstream infections in hospitalized patients all over the world. It remains associated with high mortality., [Objectives] To assess the impact of implementing an evidence-based package of measures (bundle) on the quality of care and outcomes of candidaemia., [Methods] A systematic review of the literature was performed to identify measures related to better outcomes in candidaemia. Eight quality-of-care indicators (QCIs) were identified and a set of written recommendations (early treatment, echinocandins in septic shock, source control, follow-up blood culture, ophthalmoscopy, echocardiography, de-escalation, length of treatment) was prospectively implemented. The study was performed in 11 tertiary hospitals in Spain. A quasi-experimental design before and during bundle implementation (September 2016 to February 2018) was used. For the pre-intervention period, data from the prospective national surveillance were used (May 2010 to April 2011)., [Results] A total of 385 and 263 episodes were included in the pre-intervention and intervention groups, respectively. Adherence to all QCIs improved in the intervention group. The intervention group had a decrease in early (OR 0.46; 95% CI 0.23–0.89; P = 0.022) and overall (OR 0.61; 95% CI 0.4–0.94; P = 0.023) mortality after controlling for potential confounders., [Conclusions] Implementing a structured, evidence-based intervention bundle significantly improved patient care and early and overall mortality in patients with candidaemia. Institutions should embrace this objective strategy and use the bundle as a means to measure high-quality medical care of patients., This study was funded by a research grant from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (FIS PI15/00744). This study is also co-financed by the European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD06/0008). The funding institutions had no role in the design or performance of the research. C.G.-V. is a recipient of an INTENSIFICACIÓ Grant from the ‘Strategic plan for research and innovation in health-PERIS 2016–2020’ and forms part of the FungiCLINIC Research group (AGAUR-Project 2017SGR1432 of the Catalan Health Agency).

Standards on tissue banking determine the need of microbiological monitoring during critical steps (recovery, processing, storage, and transplantation). This information will be useful for both discarding contaminated tissues or risk analysis (in case of recipient infection). In this study, we show the case of a multiorgan-multitissue donor colonized by Candida auris. This microorganism is characterized by multidrug resistance, with higher transmissibility and severe outcome. Some of the microbiological cultures from arteries tested positive for this microorganism, but it was not cultured in samples from musculoskeletal tissues and corneas. No recipient case of infection transmission by Candida species was observed (organs and cornea). The implementation of active surveillance protocol for C. auris detection in critical care units (as source of tissue donors) has been suggested as a part of our hospitals' infection control policy.

Background Despite being considered a high-risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized. Methods We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010-2011) and the CANDI-Bundle Study (2016-2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all-cause 7-day mortality and/or persistent candidemia for >= 72 hours) and 30-day mortality were investigated by univariate analysis. Results We included 55 episodes of post-transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non-susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30-day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03-0.85; P-value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03-0.76; P-value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02-0.89; P-value = .041) were protective for 30-day mortality. Conclusions High rates of non-albicans species and fluconazole non-susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia.

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex, 157 C. guilliermondii (Meyerozyma guilliermondii), 676 C. krusei (Pichia kudriavzevii), 298 C. lusitaniae (Clavispora lusitaniae), 911 C. parapsilosis sensu stricto, 3,691 C. parapsilosis species complex, 36 C. metapsilosis, 110 C. orthopsilosis, 1,854 C. tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A. flavus, 130 A. nidulans, 233 A. Niger, and 302 A. terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2 and CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 g/ml for C. albicans and the Etest itraconazole ECV of 2 g/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants. Copyright © 2018 American Society for Microbiology. All Rights Reserved.

CANDIPOP Project, the CANDI‐Bundle Group GEIRAS‐GEMICOMED (SEIMC) REIPI., [Background] Despite being considered a high‐risk population for invasive fungal disease, specific features of candidemia among solid organ transplant (SOT) recipients remain poorly characterized., [Methods] We compiled prospective data from two multicenter studies on candidemia performed over two consecutive periods in Spain: the CANDIPOP Study (2010‐2011) and the CANDI‐Bundle Study (2016‐2018). Episodes diagnosed in adult SOT recipients in 10 participating centers were included. Risk factors for clinical failure (all‐cause 7‐day mortality and/or persistent candidemia for ≥72 hours) and 30‐day mortality were investigated by univariate analysis., [Results] We included 55 episodes of post‐transplant candidemia (32 and 23 of which occurred during the first and second periods). Kidney (38.2%) and liver recipients (30.9%) were the most common populations. Candida albicans accounted for 27.3% of episodes. The proportion of C glabrata increased over time (18.8% vs 30.4% for the first and second periods). There were no differences in the rate of fluconazole non‐susceptible isolates (50.0% vs 60.0%, respectively). Clinical failure and 30‐day mortality occurred in 25.5% and 27.3% of episodes and were associated with the severity of candidemia (Pitt score and severe sepsis/septic shock). Kidney transplantation (unadjusted odds ratio [uOR]: 0.17; 95% confidence interval [CI]: 0.03‐0.85; P ‐value = .020), early catheter removal (uOR: 0.15; 95% CI: 0.03‐0.76; P ‐value = .013), and appropriate early antifungal therapy (uOR: 0.14; 95% CI: 0.02‐0.89; P ‐value = .041) were protective for 30‐day mortality., [Conclusions] High rates of non‐albicans species and fluconazole non‐susceptibility must be taken into account to optimize therapeutic management and outcomes in SOT recipients with candidemia., The CANDIPOP Project was supported by non‐restrictive research grants from Gilead Sciences, MSD, Astellas Pharma, and Pfizer. This study was cofounded by Fundación SEIMC‐GESIDA, by the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III (co‐financed by the European Development Regional Fund [ERDF] >A way to achieve Europe>), and by the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015). The CANDI‐Bundle Study was supported by “Plan Nacional de I + D+I” and Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias [FIS] PI15/00744), Subdirección General de Redes y Centros de Investigación Cooperativa, Spanish Ministry of Science, Innovation and Universities, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016). MFR holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III.

Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplantation, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present 3 complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung transplantation. In 2 of 3 cases, the infection was clinically and radiologically cured with frequent cleansing bronchoscopies, combining triazole with terbinafine therapy and nebulized posaconazole. These cases highlight the importance of adjunctive nebulized therapy in addition to prolonged triazole treatment to manage complex invasive Scedosporium infections in immunosuppressed patients. Posaconazole (PSZ) was delivered during the bronchoscopy procedure through intrabronchial administration, whereas an eFlow rapid((R)) device was used for nebulized therapy. Topical posaconazole was well tolerated in 2 patients, with only a slight cough during administrations; the third patient had local irritation with poor tolerance, which led to its withdrawal. This is the first report on compassionate use of topical PSZ as salvage therapy for resistant mold infections in lung transplant recipients. These 3 cases represent the entire experience using this approach; no additional patients have received this therapy due to there not having been any additional cases of Scedosporium tracheobronchitis presented.

A case of 1-year-old male multivisceral transplant recipient with candidemia diagnosed by the T2Candida (R) test is presented. Optimal management of the candidemia complemented the treatment of the global clinical episode. Duration of treatment might be established much more precisely with the T2Candida (R) test than with blood cultures.

Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.

The prognosis of invasive fungal infections (IFI) depends on the speed of diagnosis and treatment. Conventional diagnostic methods are of low sensitivity, laborious and too slow, leading to the need for new, faster, and more efficient diagnostic strategies. There are several techniques for diagnosing a candidemia that are faster than the conventional blood culture (BC). Once yeast growth in BC is detected, species identification can be speeded up by mass spectrometry (30 minutes), commercialised molecular techniques (60-80 minutes) or fluorescent in situ hybridization (90 minutes). The combined detection of biomarkers (antimicellium, mannan and antimannan or beta-glucan) has shown to be of greater use than their individual use. Commercialised nucleic acid amplification techniques (Septifast (R), T2Candida (R)) are very reliable alternatives to BC. The detection of the capsular antigen of Cryptococcus, by means of latex agglutination or immuno-chromatography, is a valuable technique for cryptococcosis diagnosis. Direct microscopic examination and culture of representative specimens is used for the conventional diagnosis of IFI by filamentous fungi. Detection of galactomannan and beta-glucan are considered diagnostic criteria for probable invasive aspergillosis and probable IFI, respectively, despite the lack of specificity of the latter. The detection of fungal volatile organic compounds in breath is an interesting diagnostic strategy in pulmonary infections. Although widely used, nucleic acid detection techniques are not considered diagnostic criteria for IFIs caused by moulds in consensus documents, due to their lack of standardisation. However, they are the only alternative to culture methods in invasive infections by Scedosporium/Lomentospora, Fusarium, zygomycetes, or dematiaceous fungi. (C) 2018 Asociacion Espahola de Micologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Background: Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and is associated with high mortality. It is typically resistant to fluconazole and voriconazole and, some cases, also to echinocandins and amphotericin B. This species, phylogenetically related to Candida haemulonii, is frequently misidentified by commercial identification techniques in clinical laboratories; therefore, the real prevalence of C auris infections may be underestimated. Aims: To describe the clinical and microbiological features of the first four cases of C auris fungemia episodes observed" in the European continent. Methods: The four patients were hospitalized in the adult surgical intensive care unit. A total of 8 isolates (two per patient) from blood and catheter tip were analyzed. Results: All isolates were misidentified as Saccharomyces cerevisiae by AuxaColor 2, and as Candida sake by API ID20C. VITEK MS technology misidentified one isolate as Candida lusitaniae, another,as C haemulonii and could not identify the other six. C auris identification was confirmed by ITS rDNA sequencing. All isolates were fluconazole (MIC >256 mg/I) and voriconazole (MIC 2 mg/1) resistant and susceptible to posaconazole, itraconazole, echinocandins and amphotericin B. Conclusions: C auris should be regarded as an emerging pathogen, which requires molecular methods for definitive identification. Our isolates were highly resistant to fluconazole and resistant to voriconazole, but susceptible to the other antifungals tested, which emphasizes the importance of accurately identifying this species to avoid therapeutic failures. (C) 2016 Asociacion Espanola de Micologia. Published by Elsevier Espafla, S.L.U. All rights reserved.

Background: Current therapeutic strategies have a limited efficacy against Candida biofilms that form on the surfaces of biomedical devices. Few studies have evaluated the activity of antifungal agents against Candida tropicalis biofilms. Objectives: To evaluate the activity of amphotericin B (AMB) and anidulafungin (AND), alone and in combination, against C tropicalis biofilms developed on polytetrafluoroethylene (teflon -PTFE) and titanium surfaces using time-kill assays. Methods: Assays were performed using the CDC Biofilm Reactor equipped with PTFE and titanium disks with C. tropicalis biofilms after 24 h of maturation. The concentrations assayed were 40 mg/l for AMB and 8 mg/l for AND, both alone and combined. After 24, 48 and 72 h of exposure to the antifungals, the cfu/cm(2) was determined by a vortexing-sonication procedure. Results: AMB reduced biofilm viable cells attached to PTFE and titanium by >= 99% and AND by 89.3% on PTFE and 96.8% on titanium. The AMB +AND combination was less active than AMB alone, both on PTFE (decrease of cfu/cm(2) 3.09 Log(10) vs. 1.08 when combined) and titanium (4.51 vs. 1.53 when combined), being the interaction irrelevant on both surfaces. Conclusions: AMB is more active than AND against C. tropicalis biofilms. Yeast killing rates are higher on titanium than on PTFE surfaces. The combination of AMB plus AND is less effective than AMB alone on both surfaces. (C) 2017 Asociacion Espanola de Micologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Background: Although the management of the invasive candidiasis has improved in the last decade, controversial issues yet remain, especially in the diagnostic and therapeutic approaches to Candida peritonitis and other forms of intra-abdominal fungal infections. Aims: We sought to identify core clinical knowledge about intra-abdominal fungal infections and to achieve high-agreement recommendations required to care for critically ill adult patients with Candida peritonitis and other forms of intra-abdominal fungal infection. Methods: A biregional Spanish survey, to elucidate the consensus about the already mentioned fungal infections by means of the Delphi technique, was conducted anonymously by e-mail with 29 multidisciplinary experts in invasive fungal infections from 14 hospitals in the Valencia and Murcia communities during 2014. Respondents included intensivists, anesthesiologists, microbiologists, pharmacologists, and infectious disease specialists, who answered 31 questions prepared by a coordination group after a strict review of the literature from the 5 previous years. The educational objectives spanned 6 categories: epidemiology, microbiological diagnosis, clinical diagnosis, antifungal treatment, de-escalation therapy, and special situations. The agreement required among the panelists for each item to be selected had to be higher than 70%. After extracting the recommendations from the selected items, a meeting at which the experts were asked to validate the previously selected recommendations in a second round of scoring took place. Results: After the second round, 36 recommendations were validated according to the following distribution: epidemiology (5), microbiological diagnosis (4), clinical diagnosis (4), antifungal treatment (3), de-escalation therapy (4), and special situations (16). Conclusions: Treatment of Candida peritonitis and other forms of intra-abdominal fungal infections in ICU patients requires a broad range of knowledge application and skills that our recommendations address. Based on the DELPHI methodology, these recommendations might help to optimize the therapeutic management of these patients in special situations and in various scenarios to improve their outcome. (C) 2017 Asociacion Espanola de Micologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Invasive candidiasis in non-neutropenic critically ill patients remains a challenge for clinicians due to its association with high morbidity and mortality rates, increased incidence, and health-care costs. It is well known that early diagnosis and treatment are associated with a better prognosis. For these reasons a thorough update has been performed in this setting focused on recent Spanish epidemiology, new predictive scores and microbiological tests such as mannan antigen, mannan antibodies, Candida albicans germ-tube antibodies or (1 -> 3)-beta-D-glucan detection, molecular techniques for the detection of fungal specific DNA, advances in antifungal treatment and educational programs in Spain. An early diagnostic and therapeutic algorithm is proposed based on the combination of scores and microbiological test. The aim of this review is to provide physicians with the best information available in order to improve the prognosis of these patients. (C) 2016 Asociacion Espanola de Micologia. Published by Elsevier Espana, S.L.U. All rights reserved.

A prospective, observational, multicentre study of invasive candidosis (IC) in surgical patients in intensive care units (ICUs) was conducted from 2006 to 2008 in 72 ICUs in 14 European countries. A total of 779 patients (62.5% males, median age 63 years) with IC were included. The median rate of candidaemia was 9 per 1000 admissions. In 10.8% the infection was already present at the time of admission to ICU. Candida albicans accounted for 54% of the isolates, followed by Candida parapsilosis 18.5%, Candida glabrata 13.8%, Candida tropicalis 6%, Candida krusei 2.5%, and other species 5.3%. Infections due to C.krusei (57.9%) and C.glabrata (43.6%) had the highest crude mortality rate. The most common preceding surgery was abdominal (51.5%), followed by thoracic (20%) and neurosurgery (8.2%). Candida glabrata was more often isolated after abdominal surgery in patients ≥60 years, and C.parapsilosis was more often isolated in neurosurgery and multiple trauma patients as well as children ≤1 year of age. The most common first-line treatment was fluconazole (60%), followed by caspofungin (18.7%), liposomal amphotericin B (13%), voriconazole (4.8%) and other drugs (3.5%). Mortality in surgical patients with IC in ICU was 38.8%. Multivariate analysis showed that factors independently associated with mortality were: patient age ≥60 years (hazard ratio (HR) 1.9, p 0.001), central venous catheter (HR 1.8, p 0.05), corticosteroids (HR 1.5, p 0.03), not receiving systemic antifungal treatment for IC (HR 2.8, p

To update the knowledge of the epidemiology of fungaemia episodes in Spain, the species implicated and their in vitro antifungal susceptibilities. Episodes were identified prospectively over 13 months at 44 hospitals. Molecular methods were used to determine the cryptic species inside the Candida parapsilosis and Candida glabrata complexes. Susceptibility to amphotericin B, anidulafungin, caspofungin, fluconazole, flucytosine, itraconazole, micafungin, posaconazole and voriconazole was determined by a microdilution colorimetric method. New species-specific clinical breakpoints (SSCBPs) for echinocandins, fluconazole and voriconazole were applied. The incidence of the 1357 fungaemia episodes evaluated was 0.92 per 1000 admissions. The incidence of Candida albicans fungaemia was the highest (0.41 episodes/1000 admissions), followed by Candida parapsilosis sensu stricto (0.22). Candida orthopsilosis was the fifth cause of fungaemia (0.02), outnumbered by Candida glabrata and Candida tropicalis. Interestingly, the incidence of fungaemia by C. parapsilosis was 11 and 74 times higher than that by C. orthopsilosis and Candida metapsilosis, respectively. Neither Candida nivariensis nor Candida bracarensis was isolated. Fungaemia was more common in non-intensive care unit settings (65.2) and among elderly patients (46.4), mixed fungaemia being incidental (1.5). Overall susceptibility rates were 77.6 for itraconazole, 91.9 for fluconazole and 96.599.8 for the other agents. Important resistance rates were only observed in C. glabrata for itraconazole (24.1) and posaconazole (14.5), and in Candida krusei for itraconazole (81.5). Fungaemia is more common in non-critical patients. C. albicans is the most common species, followed by C. parapsilosis and C. glabrata. Nearly 90 of yeasts are susceptible to all antifungal agents tested. Resistance rates change moderately when applying the new SSCBPs.