Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) ...prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.
EUCAST has revised the definition of the susceptibility category I from ‘Intermediate’ to ‘Susceptible, Increased exposure’. This implies that I can be used where the drug concentration at the site ...of infection is high, either because of dose escalation or through other means to ensure efficacy. Consequently, I is no longer used as a buffer zone to prevent technical factors from causing misclassifications and discrepancies in interpretations. Instead, an Area of Technical Uncertainty (ATU) has been introduced for MICs that cannot be categorized without additional information as a warning to the laboratory that decision on how to act has to be made. To implement these changes, the EUCAST-AFST (Subcommittee on Antifungal Susceptibility Testing) reviewed all, and revised some, clinical antifungal breakpoints.
The aim was to present an overview of the current antifungal breakpoints and supporting evidence behind the changes.
This document is based on the ten recently updated EUCAST rationale documents, clinical breakpoint and breakpoint ECOFF documents.
The following breakpoints (in mg/L) have been revised or established for Candida species: micafungin against C. albicans (ATU = 0.03); amphotericin B (S ≤/> R = 1/1), fluconazole (S ≤/> R = 2/4), itraconazole (S ≤/> R = 0.06/0.06), posaconazole (S ≤/> R = 0.06/0.06) and voriconazole (S ≤/> R = 0.06/0.25) against C. dubliniensis; fluconazole against C. glabrata (S ≤/> R = 0.001/16); and anidulafungin (S ≤/> R = 4/4) and micafungin (S ≤/> R = 2/2) against C. parapsilosis. For Aspergillus, new or revised breakpoints include itraconazole (ATU = 2) and isavuconazole against A. flavus (S ≤/> R = 1/2, ATU = 2); amphotericin B (S ≤/> R = 1/1), isavuconazole (S ≤ /> R = 1/2, ATU = 2), itraconazole (S ≤/> R = 1/1, ATU = 2), posaconazole (ATU = 0.25) and voriconazole (S ≤/> R = 1/1, ATU = 2) against A. fumigatus; itraconazole (S ≤/> R = 1/1, ATU = 2) and voriconazole (S ≤/> R = 1/1, ATU = 2) against A. nidulans; amphotericin B against A. niger (S ≤/> R = 1/1); and itraconazole (S ≤/> R = 1/1, ATU = 2) and posaconazole (ATU = 0.25) against A. terreus.
EUCAST-AFST has released ten new documents summarizing existing and new breakpoints and MIC ranges for control strains. A failure to adopt the breakpoint changes may lead to misclassifications and suboptimal or inappropriate therapy of patients with fungal infections.
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 <0.0001), and not removing intravascular lines (HR 1.6, p 0.02).
Abstract
Objectives
To generate antifungal susceptibility patterns for Trichomonascus ciferrii (Candida ciferrii), Candida inconspicua (Torulopsis inconspicua) and Diutina rugosa species complex ...(Candida rugosa species complex), and to provide key parameters such as MIC50, MIC90 and tentative epidemiological cut-off values (TECOFFs).
Methods
Our strain set included isolates of clinical origin: C. inconspicua (n = 168), D. rugosa species complex (n = 90) Candida pararugosa (n = 60), D. rugosa (n = 26) and Candida mesorugosa (n = 4), Pichia norvegensis (Candida norvegensis) (n = 15) and T. ciferrii (n = 8). Identification was performed by MALDI-TOF MS or internal transcribed spacer sequencing. Antifungal susceptibility patterns were generated for azoles, echinocandins and amphotericin B using commercial Etest and the EUCAST broth microdilution method v7.3.1. Essential agreement (EA) was calculated for Etest and EUCAST.
Results
C. inconspicua, C. pararugosa and P. norvegensis showed elevated azole MICs (MIC50 ≥0.06 mg/L), and D. rugosa and C. pararugosa elevated echinocandin MICs (MIC50 ≥0.06 mg/L). EA between methods was generally low (<90%); EA averaged 77.45%. TECOFFs were suggested for C. inconspicua and D. rugosa species complex.
Conclusions
Rare yeast species tested shared high fluconazole MICs. D. rugosa species complex displayed high echinocandin MICs, while C. inconspicua and P. norvegensis were found to have high azole MICs. Overall, the agreement between EUCAST and Etest was poor and therefore MIC values generated with Etest cannot be directly compared with EUCAST results.
The Fluorescence detector Array of Single-pixel Telescopes (FAST) is a design concept for a next-generation UHECR observatory, addressing the requirements for a large-area, low-cost detector suitable ...for measuring the properties of ultra-high energy cosmic rays (UHECRs), having energies exceeding 30 EeV, with an unprecedented aperture. We have developed a full-scale prototype consisting of four 200 mm diameter photo-multiplier tubes at the focus of a segmented mirror of 1.6 m in diameter. In October 2016, September 2017, and September 2018 we installed three such prototypes at the Black Rock Mesa site of the Telescope Array experiment in central Utah, USA. All three telescopes have been steadily taking data since installation. We report on the design and installation of these prototypes, and present some preliminary results, including measurements of artificial light sources, distant ultraviolet lasers, and UHECRs.
A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections.
A total of ...370 cases from 21 countries were evaluated.
The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L).
Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.
In order to better understand the epidemiology of fusariosis in Europe, a survey collecting information on the clinical characteristics of the patients infected by
Fusarium
as well as on the ...infecting isolates was launched. A total of 76 cases of invasive fusariosis occurring from January 2007 to June 2012 were collected and
Fusarium
isolates were identified by sequencing the translation elongation factor 1α (TEF) gene. Also, antifungal susceptibility was tested by broth microdilution according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Etest. Disseminated disease was considered proven in 46 cases and probable in 17 cases. Localised infection was seen in 13 cases.
Gibberella fujikuroi
species complex (SC), including
Fusarium verticillioides
and
F. proliferatum
, and
F. solani
SC were the most frequent aetiology of disseminated and localised infections, respectively. The crude mortality rate was 46 %, the highest associated with
F. solani
SC (67 %) and
F. proliferatum
(62.5 %). A wide range of antifungal susceptibilities was observed. Amphotericin B was the most potent antifungal in vitro, and itraconazole the least effective. The azoles exhibited lower minimum inhibitory concentrations (MICs) against
F. verticillioides
strains, with posaconazole having a slightly better performance, while
F. solani
SC isolates were resistant to all three azoles tested. The essential agreement between the Etest and the EUCAST method was 100 % for itraconazole and voriconazole, and 96 % for amphotericin B and posaconazole. In conclusion, we confirm that fusariosis is a rare but severe event in Europe, that
G. fujikuroi
SC is the predominant cause of deep infections and that different species have different antifungal in vitro susceptibility patterns.
Summary
Detection of serum galactomannan (GM) and (1,3)‐β‐d‐glucan (BG) is considered useful for non‐culture diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Only few ...studies evaluated these seromarkers in non‐neutropenic patients suspected of having IPA. The aim of this study was to evaluate both tests together with the Aspergillus fumigatus‐specific serum IgG and IgA (IgAG) test for serological IPA diagnosis in non‐neutropenic patients. Sera from 87 patients suspected of having IPA were retrospectively analysed. Patients were categorised into groups of proven IPA (n = 10), putative IPA (n = 31) and non‐IPA colonisation (n = 46). When the GM, BG and IgAG assays were used for patients included in the study, the sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) were 48.8%/91.3%/83.3%/66.7%, 82.9%/73.9%/73.9%/82.9% and 75.6%/95.7%/93.9%/81.5%, respectively. Thus, the highest specificity and PPV were confirmed for the IgAG assay. Improvements in the sensitivity and NPV were achieved by “at least one positive” analysis with the GM and BG assays, with the sensitivity/specificity/PPV/NPV values being 85.0%/69.6%/71.4%/84.2%. Nevertheless, the highest sensitivity and NPV were achieved by the “at least one positive” analysis combining the GM, BG and IgAG tests (97.6% and 96.8%, respectively). The involvement of the IgAG assay could improve IPA diagnosis in non‐neutropenic patients by increasing the sensitivity and NPV when combined with the GM or BG assays. Furthermore, improvement was achieved by combining the GM, BG and IgAG assays using the “at least one positive test” strategy, especially if doubt exists.
Trichophyton erinacei is a main cause of dermatophytosis in hedgehogs and is increasingly reported from human infections worldwide. This pathogen was originally described in the European hedgehog ( ...Erinaceus europaeus ) but is also frequently found in the African four-toed hedgehog ( Atelerix albiventris ), a popular pet animal worldwide. Little is known about the taxonomy and population genetics of this pathogen despite its increasing importance in clinical practice. Notably, whether there are different populations or even cryptic species associated with different hosts or geographic regions is not known. To answer these questions, we collected 161 isolates, performed phylogenetic and population-genetic analyses, determined mating-type, and characterised morphology and physiology. Multigene phylogeny and microsatellite analysis supported T. erinacei as a monophyletic species, in contrast to highly incongruent single-gene phylogenies. Two main subpopulations, one specific mainly to Atelerix and second to Erinaceus hosts, were identified inside T. erinacei , and slight differences in the size of microconidia and antifungal susceptibilities were observed among them. Although the process of speciation into two lineages is ongoing in T. erinacei , there is still gene flow between these populations. Thus, we present T. erinacei as a single species, with notable intraspecies variability in genotype and phenotype. The data from wild hedgehogs indicated that sexual reproduction in T. erinacei and de novo infection of hedgehogs from soil are probably rare events and that clonal horizontal spread strongly dominates. The molecular typing approach used in this study represents a suitable tool for further epidemiological surveillance of this emerging pathogen in both animals and humans. The results of this study also highlighted the need to use a multigene phylogeny ideally in combination with other independent molecular markers to understand the species boundaries of dermatophytes.
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