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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. 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 Candi Reg). 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. 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. 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. Scynexis. [ABSTRACT FROM AUTHOR]

Access to the appropriate tools is crucial for early diagnosis and clinical management of invasive fungal infections. This Review aims to describe the invasive fungal infection diagnostic capacity of Europe to better understand the status and the most pressing aspects that need improvement. To our knowledge, this is the first time that the mycological diagnostic capability and access to antifungal treatments of institutions has been evaluated at a pan-European level. Between Nov 1, 2021, and Jan 31, 2022, 388 institutions in Europe self-assessed their invasive fungal infection management capability. Of the 388 participating institutions from 45 countries, 383 (99%) had access to cultures, 375 (97%) to microscopy, 363 (94%) to antigen-detection assays, 329 (85%) to molecular tests (mostly PCR), and 324 (84%) to antibody tests for diagnosis and management. With the exception of microscopy, there were considerable differences in access to techniques among countries according to their gross domestic product. At least one triazole was available in 363 (94%) of the institutions, one echinocandin in 346 (89%), and liposomal amphotericin B in 301 (78%), with country gross domestic product-based differences. Differences were also observed in the access to therapeutic drug monitoring. Although Europe is well prepared to manage invasive fungal infections, some institutions do not have access to certain diagnostic tools and antifungal drugs, despite most being considered essential by WHO. These limitations need to be overcome to ensure that all patients receive the best diagnostic and therapeutic management., Competing Interests: Declaration of interests JS-G received payments or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead and Pfizer, outside of the submitted work. MH received grants or contracts from Gilead, Pfizer, Astellas, Euroimmune, MSD, Pulmocide, Scynexis, and F2G, outside of the submitted work. J-PG received grants or contracts from Pfizer, and consulting fees from Gilead and Pfizer, outside of the submitted work. AA-I received payments or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead and Pfizer; received support for attending meetings and travel from Gilead; participated on a data safety monitoring board or advisory board for JPI-AMR; and had a leadership or fiduciary role in board, society, committee or advocacy groups that were either paid or unpaid, from WHO, European Society of Clinical Microbiology and Infectious Diseases, Fungal Infection Study Group, and Global Action For Fungal Infections, outside of the submitted work. KL received grants or contracts from Thermo Fisher Scientific and TECOmedical; consulting fees from Gilead, MSD, and MRM Health; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Pfizer, Gilead, and FUJIFILM Wako, outside of the submitted work. SAA reports grants or contracts from Cidara; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead; and support for attending meetings and travel from Astellas, outside of the submitted work. VÖ received grants or contracts from International Health Management Associates and Sentry, outside of the submitted work. OAC received grants or contracts from Amplyx, Basilea, Bundesministerium für Bildung und Forschung, Cidara, Deutsches Zentrum für Infektionsforschung, EU Directorate-General for Research and Innovation (grant: 101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from AbbVie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, Mycoses Study Group Education and Research Consortium (MSG-ERC), Noxxon, Octapharma, Pardes, PSI, Scynexis, and Seres; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck-MSD, Mylan, and Pfizer; payment for expert testimony from Cidara; patents planned, issued, or pending from the German Patent and Trademark Office; participation on a data safety monitoring board or advisory board for Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, and Shionogi; and other financial or non-financial interests from Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie, Deutsche Gesellschaft für Information und Wissen, European Confederation of Medical Mycology, International Society for Human and Animal Mycology, MSG-ERC, and Wiley, outside of the submitted work. ES and AV declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the United States ( n  = 13) and Europe ( n  = 3). First, on testing of 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true-positive and 97.2% true-negative results. Second, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC positive and PCR/ESI-MS negative, 4.3%; BC positive and PCR/ESI-MS positive, 10.3%; BC negative and PCR/ESI-MS positive, 15.3%; and BC negative and PCR/ESI-MS negative, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were >94% for all individual species. Patients who had received prior antimicrobial medications ( n  = 603) had significantly higher PCR/ESI-MS positivity rates than patients without prior antimicrobial treatment-31% versus 22% ( P  < 0.0001)-with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics to be used with whole blood for detection of bloodstream microorganisms in sepsis., (Copyright © 2020 Strålin et al.)