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Background: The epidemiology of candidemia has changed over the last decades and varies widely among geographic areas., Aims: We examined in children (aged 0-14) with candidemia the trends in the incidence rate of this infection, as well as the clinical characteristics of the patients, in order to optimize the prognosis and the control measures of this serious disease., Methods: A retrospective cohort study of candidemia in the period 2011-2018 in the neonatal intensive care unit (NICU), pediatric ICU (PICU) and pediatric wards of a tertiary hospital, was conducted. The clinical course, Candida species isolated, antifungal susceptibility, outcome and incidence rates were analyzed and compared., Results: We diagnosed 68 episodes of candidemia in 62 children, 48% occurred in the NICU, 31% in the PICU and 21% in pediatric wards. Candida albicans was the most frequent species isolated in NICU infants (53%), and Candida parapsilosis predominated among PICU patients (59%) and pediatric wards (50%). One third of NICU infants had invasive candidiasis (IC), most of them having extremely low birth weight (ELBW) (35%). All isolates were susceptible to the antifungal administered. Over time, the incidence of candidemia decreased in the PICU (from 2.2 to 0.3 episodes/1000 patient-days, OR=0.6; 95%CI 0.5-0.8), whereas in the NICU and in the wards remained stable. Mortality occurred mostly in NICU patients (26%), predominated in ELBW infants and did not change over time., Conclusions: The higher incidence and mortality of candidemia and IC observed in preterm infants requires a continuous evaluation of practices and diagnostic methods which will allow improving the prognosis of this most vulnerable population., (Copyright © 2020 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Candida parapsilosis, Candida metapsilosis and Candida orthopsilosis are emerging as relevant causes of candidemia. Moreover, they show differences in their antifungal susceptibility and virulence. The echinocandins are different in terms of in vitro antifungal activity against Candida. Time-kill (TK) curves represent an excellent approach to evaluate the fungicidal activity of antifungal drugs., Aims: To compare the fungicidal activities of anidulafungin, caspofungin and micafungin against C. parapsilosis species complex by TK curves., Methods: Antifungal activities of three echinocandins against C. parapsilosis, C. metapsilosis and C. orthopsilosis were studied by TK curves. Drug concentrations assayed were 0.25, 2 and 8μg/ml. CFU/ml were determined at 0, 2, 4, 6, 24 and 48h., Results: Killing activities of echinocandins were species-, isolates- and concentration-dependent. Anidulafungin reached the fungicidad endpoint for 6 out of 7 isolates (86%); it required between 13.34 and 29.67h to reach this endpoint for the three species studied, but more than 48h were needed against one isolate of C. orthopsilosis (8μg/ml). Caspofungin fungicidal endpoint was only achieved with 8μg/ml against one isolate of C. metapsilosis after 30.12h (1 out of 7 isolates; 14%). Micafungin fungicidal endpoint was reached in 12.74-28.38h (8μg/ml) against one isolate each of C. parapsilosis and C. orthopsilosis, and against both C. metapsilosis isolates (4 out of 7 isolates; 57%)., Conclusions: C. metapsilosis was the most susceptible species to echinocandins, followed by C. orthopsilosis and C. parapsilosis. Anidulafungin was the most active echinocandin against C. parapsilosis complex., (Copyright © 2019 Asociación Española de Micología. Publicado por Elsevier España, 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 24h of maturation. The concentrations assayed were 40mg/l for AMB and 8mg/l for AND, both alone and combined. After 24, 48 and 72h 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., (Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, 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 >256mg/l) and voriconazole (MIC 2mg/l) 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., (Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The number of biomedical devices (intravascular catheters, heart valves, joint replacements, etc.) that are implanted in our hospitals has increased exponentially in recent years. Candida species are pathogens which are becoming more significant in these kinds of infections. Candida has two forms of development: planktonic and in biofilms. A biofilm is a community of microorganisms which adhere to a surface and are enclosed by an extracellular matrix. This form of development confers a high resistance to the antimicrobial agents. This is the reason why antibiotic treatments usually fail and biomedical devices may have to be removed in most cases. Unspecific adhesion mechanisms, the adhesion-receptor systems, and an intercellular communication system called quorum sensing play an essential role in the development of Candida biofilms. In general, the azoles have poor activity against Candida biofilms, while echinocandins and polyenes show a greater activity. New therapeutic strategies need to be developed due to the high morbidity and mortality and high economic costs associated with these infections. Most studies to date have focused on bacterial biofilms. The knowledge of the formation of Candida biofilms and their composition is essential to develop new preventive and therapeutic strategies., (Copyright © 2014 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Recent epidemiological surveillance studies have reported an increase in fungaemia caused by non-Candida albicans species, as well as a decrease in fluconazole susceptibility., Objectives: To evaluate changes in the epidemiology of fungaemia in Spain comparing data from a new surveillance epidemiological study conducted in 2009 with a previous study carried out from 1997 to 1999 (Pemán J, et al. Eur J Clin Microbiol Infect Dis. 2005)., Methods: From January 2009 to February 2010, 44 Spanish hospitals participated in a prospective multicentre fungaemia surveillance study to ascertain whether there have been changes in the epidemiology and fluconazole susceptibility. Susceptibility was determined by the colorimetric method Sensititre Yeast One. Demographic and clinical data and the first isolate of each episode were gathered., Results: A total of 1,377 isolates from 1,357 fungaemia episodes were collected, 46.7% from patients older than 64years and 8.6% from children less than 1 year old. C. albicans (44.7%), Candida parapsilosis (29.1%), Candida glabrata (11.5%), Candida tropicalis (8.2%), and Candida krusei (1.9%) were the most frequent species isolated. Distribution varied with the geographical area. C. albicans incidence has increased significantly in the last 10years in Cataluña (39.1 vs. 54.7%, P=0.03) and decreased in the Valencian Community (49.1 vs. 34.6%, P=0.002) and Extremadura (58.3 vs. 20%, P=0.01). Susceptibility to fluconazole was similar for all geographical areas, although resistance in C. albicans was ten times greater for patients aged more than 64years. The overall rate of fluconazole resistance (MIC > 32 mg/L) has decreased with respect to that obtained 10years ago (3.7 vs. 2.5%) mainly in C. albicans (3 vs. 1.6%)., Conclusions: In the last ten years, species distribution and fluconazole susceptibility have not significantly changed, although a lower rate of fluconazole resistance has been observed. Species distribution varies with hospital, hospitalization Unit and geographical area., (Copyright © 2010 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Background: Micafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses with a wide antifungal spectrum for the most common pathogenic fungi. Micafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3- D-glucan synthesis, an essential molecule for the cell wall architecture, with different con sequences for Candida and Aspergillus, being micafungin fungicide for the former and fungistatic for the latter., Aim: To describe the in vitro antifungal spectrum of micafungin based in the scientific and medical lite rature of recent years., Methods: We have done a bibliographic retrieval using the scientific terms, "micafungin", "activity", "Candida", "Aspergillus", "fungi", "mycos*", "susceptibility", in PubMed/Medline from the National Library of Medicine de EE.UU. from 2005 to 2009., Results: We can underline that most than 99% of Candida isolates are susceptible to < or = 2microg/ml of micafungin. MIC are very low (< or = 0.125microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2microg/ml. The activity of micafungin is excellent against those medical important species of Aspergillus. However, its activity is very low against Cryptococcus and the Zygomycetes., Conclusions: The excellent activity of micafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.

Currently, no standardized method to study the in vitro activity of antifungal agents on biofilms is available, thus, the comparison among different authors is difficult. The studies discussed in this review use the XTT reduction to measure the activity of antifungals on biofilms of 24 h of maturation. To date, biofilm anidulafungin MICs of 47 isolates of Candida spp. (25 Candida albicans, 16 Candida tropicalis, 5 Candida dubliniensis and 1 Candida parapsilosis) have been published. The geometric mean MIC of anidulafungin on biofilms of Candida spp. is of 1.18 microg/ml. Against isolates of species with great capacity of biofilm formation, the geometric mean MIC is 0.325 (C. albicans), 2 (C. parapsilosis) and 0.5 microg/ml (C. dubliniensis). No echinocandin has activity on C. tropicalis biofilms. In addition, anidulafungin can be used for lock therapy of catheters since it is the echinocandin with the least in vitro paradoxical effect.

Invasive infections caused by Candida spp. are increasing worldwide and are becoming an important cause of morbidity and mortality in immunocompromised patients. A large number of manifestations of candidiasis are associated with the formation of biofilms on inert or biological surfaces. Candida spp. biofilms are recalcitrant to treatment with conventional antifungal therapies. The aim of this study was dual 1) to determine the prevalence of biofilm producers among clinical isolates from catheter (16 C. albicans ) and blood culture (2 C. albicans and 30 C. tropicalis), and 2) to determine the activity of amphotericin B and anidulafungin against C. albicans and C. tropicalis biofilms of 24 and 48 hours of maturation. Biofilms were developed using a 96-well microtitre plate model and production and activity of antifungal agents against biofilms were determined by the tetrazolium (XTT) reduction assay. Of catheter and blood isolates, 62.5 and 56.25%, respectively, produced biofilms. By species, 68.42% of C. albicans and 53.33% of C. tropicalis were biofilm producers. C. albicans biofilms showed more resistance to amphotericin B and anidulafungin than their planktonic counterparts. Complete killing of biofilms was never achieved, even at the highest concentrations of the drugs tested. Anidulafungin displayed more activity than amphotericin B against C. albicans biofilms of 24 hours of maturation (GM MIC 0.354 vs. 0.686 microg/ml), but against C. tropicalis biofilms amphotericin B was more active (GM MIC 11.285 vs. 0.476 microg/ml). In contrast, against biofilms with 48 hours maturation, amphotericin B was more active against both species.

Voriconazole has been developed to meet the increasing need for new and useful antifungal agents for the treatment of invasive mycoses. This review describes the spectrum of voriconazole antifungal activity based on data from in vitro studies published during the last three years. This survey demonstrates that voriconazole has a broad antifungal spectrum against the most common fungal pathogens being its action fungistatic for Candida and fungicidal for Aspergillus and other filamentous fungi. Overall, more than 95% of all Candida isolates tested are susceptible to voriconazole and less than 3% are resistant. Similar or even better activity rates have been described for Aspergillus, Cryptococcus and most of yeasts and moulds of medical importance. We also discuss the limitations related to the azole cross-resistance observed in some Candida glabrata isolates, the poor activity of voriconazole against Scedosporium prolificans, its activity against fungal biofilms and the great potential usefulness of combination of voriconazole with other antifungal drugs.

Native valve endocarditis caused by Aspergillus spp. is an uncommon disease with a high mortality rate. Generally, Aspergillus is isolated from affected valve in post-mortem or biopsy specimens. However, its isolation from blood cultures is exceedingly rare. We report a case of fungal endocarditis in a native mitral valve with the isolation of Aspergillus fumigatus both in valve vegetation and in blood culture bottles. The patient underwent valve replacement and antifungal treatment with voriconazole and caspofungin, but he died on post-operative day 45 with disseminated aspergillosis confirmed by necropsy. Paradoxically, galactomannan antigen detection in serum was negative. This is the third case of Aspergillus endocarditis with positive blood culture reported in the literature.

The results of the epidemiological study on candidemias with the highest number of cases carried out in Spain is presented. This study is included in the Epidemiological Survey of Candidemia in Europe supported by the ECMM in which another five countries take part. In the Spanish study, 19 hospitals participated, 290 candidemia episodes were analysed (80 in children under 15 years and 210 in adults), 293 strains of yeasts being isolated. Both in children and in adults, the risks factors more frequently observed were the intravenous catheter and previous antibiotic therapy. In adults, the most habitual underlying disease was the solid tumor and, in children, hematological diseases. Candida albicans was the most prevalent species isolated in adults (46.1%) and Candida parapsilosis in children (50%). As part of the therapy, the intravenous line was removed and antifungal treatment was prescribed to 74% and 92.5% of children, respectively and to 43.8% and 73.8% of adults. The antifungal agent of election in adults was fluconazole (54.8%) and liposomal amphotericin B (58.1%) in children. The global mortality of the study was 38.9%, which for ages was major in adults (41.4%) than in children (38.7%). The geographical distribution of the isolated species was homogeneous, C. albicans being the predominant species, with the exception of Galicia and Extremadura where C. parapsilosis was the most frequent.