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.

Informations de copyright

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Déclaration de conflit d'intérêts

Declaration of interests MH reports grants and research funding from Astellas Pharma, Gilead Sciences, MSD, Pfizer, Euroimmun, F2G, Pulmocide, IMMY, and Mundipharma, outside of the submitted work, as well as Scynexis. JS-G has received lecture honoraria from Gilead Sciences and Pfizer, outside of the submitted work. J-PG has received lecture honoraria from Gilead Sciences, Mundipharma, and Pfizer, outside of the submitted work. TB reports receipt of speaker fees, advisory board fees, and research fellowship funding from Gilead Sciences; research grants from Pfizer and MSD; and advisory board fees from Mundipharma, all outside of the submitted work. SA-A reports research grants from Cidara Therapeutics, lecture honoraria from Gilead Sciences, and travel grants from Astellas Pharma, all outside of the submitted work. AA-I has received honoraria for educational talks on behalf of Gilead Sciences and Pfizer, outside of the submitted work. NKl was a Speaker for Astellas Pharma, Gilead Sciences, Merck/MSD, and Pfizer; and an Adviser for Gilead Sciences, Merck/MSD, and Pfizer, all outside of the submitted work. KL received consultancy fees from MRM Health, MSD, and Gilead Sciences; speaker fees from FUJIFILM Wako, Pfizer, and Gilead Sciences; and a service fee from Thermo Fisher Scientific and TECOmedical, all outside of the submitted work. NKh is a member of the Gilead Sciences, MSD, and Pfizer advisory boards for invasive fungal infections, and Chair of Pulmocide's Data and Safety Monitoring Board; and reports grants from the Swiss National Science Foundation (grant number 32003B_204944) and the National Center of Competence in Research AntiResist Grant 51NF40_180541, all outside of the submitted work. MB reports personal fees from Bayer, bioMérieux, Cidara Therapeutics, Cipla, Gilead Sciences, Menarini, MSD, Pfizer, and Shionogi, and research grants from Pfizer and MSD, all outside the submitted work. MA has received research grants from Pfizer; and honoraria from Pfizer, Gilead Sciences, and Sanofi for contributing educational activities that were paid to the university funds, all outside of the submitted work. VAA reports research funding from Pfizer outside of the submitted work. FD declares personal fees from Gilead Sciences and Pfizer, outside of the submitted work. BD reports receipt of speaker fees and advisory board fees from Gilead Sciences; and advisory board fees from Pfizer, all outside of the submitted work. GD has received lecture honoraria from Gilead Sciences and Pfizer, outside of the submitted work. GD was also invited to symposia and congresses by Gilead and Pfizer. LD reports lecture honoraria from Pfizer, MSD, and Teva Pharmaceuticals, outside of the submitted work. CG-V reports grant support from Gilead Sciences and MSD; and personal fees from Gilead Sciences, MSD, Novartis, Pfizer, Janssen, and Lilly, all outside of the submitted work. DRG reports investigator-initiated grants from Pfizer, Shionogi, and Gilead Italia; and personal fees from Pfizer and Tillotts Pharma, all outside of the submitted work. ALG reports personal fees from Jannsen, ViiV Healthcare, MSD, Bristol Myers Squibb, AbbVie, Gilead Sciences, Novartis, Pfizer, Astellas Pharma, AstraZeneca, and Angelini Pharma, outside of the submitted work. FL reports receipt of speaker fees from Gilead Sciences, Pfizer, and F2G; and advisory board fees from F2G, all outside of the submitted work. MM has received speaker fees from Janssen, Gilead Sciences, Mundipharma, MSD, and Pfizer, outside of the submitted work. JP has received research funding from MSD and Pfizer; and lecture honoraria from Gilead Sciences, Pfizer, Associates of Cape Cod, and Swedish Orphan Biovitrum, all outside of the submitted work. ER reports grants to his institutions from Astellas Pharma, MSD, Scynexis, Shionogi, GSK, Pfizer, Gilead Sciences, and Allergan; and has served as Consultant to Amplyx, Astellas Pharma, Gilead Sciences, MSD, Pfizer, Scynexis, GSK, and Shionogi, all outside of the submitted work. ORS has received speaker honoraria from Astellas Pharma, Pfizer, and Koçak Farma, outside of the submitted work. JS has received lecture honoraria from Gilead Sciences and Pfizer, outside of the submitted work. PLW has done diagnostic evaluations for, and received meeting sponsorship from, Associates of Cape Cod, Bruker, Dynamiker Biotechnology, and Launch Diagnostics; and has received speaker fees, expert advice fees, and meeting sponsorship from Gilead Sciences; speaker and expert advice fees from Pfizer; and expert advice fees from F2G, all outside of the submitted work. BW reports personal fees from MSD, Pfizer, Gilead Sciences, Shionogi, Euroimmun, IMMY, and Associates of Cape Cod; and grants to her institution from Pfizer and Shionogi, all outside of the submitted work. AMT has received lecture honoraria from Gilead Sciences, outside of the submitted work. MCA has received research grants and contract work (paid to her institution) from Amplyx, Basilea, Cidara Therapeutics, F2G, Gilead Sciences, NovaBiotics, and Scynexis; and speaker honoraria (personal fee) from Astellas Pharma, Chiesi Farmaceutici, Gilead Sciences, MSD, and SEGES, all outside of the submitted work. PK reports research funding from the German Federal Ministry of Education and Research (BMBF) B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung) and NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network) of the Network University Medicine and the State of North Rhine–Westphalia; consulting fees from Ambu, Gilead Sciences, Mundipharma, NOXXON Pharma, and Pfizer; honoraria for lectures from Akademie für Infektionsmedizin, Ambu, Astellas Pharma, Bio-Rad Laboratories, European Confederation of Medical Mycology, Gilead Sciences, Gesundheits und Pflegezentrum Academy Ruesselsheim, HELIOS Kliniken, medupdate, MedMedia, MSD, Pfizer, Scilink Comunicación Científica SC, and University Hospital LMU Munich; fees for participation on advisory boards from Ambu, Gilead Sciences, Mundipharma, and Pfizer; a pending patent currently reviewed at the German Patent and Trade Mark Office; and other non-financial interests from Elsevier, Wiley, and Taylor & Francis, all outside of the submitted work. OAC reports grants and personal fees from Actelion, Amplyx, Astellas Pharma, Basilea, Cidara Therapeutics, Da Volterra, F2G, Gilead Sciences, Medpace, Merck/MSD, and Pfizer; personal fees from Allecra Therapeutics, Al-Jazeera Pharmaceuticals, Biosys, Entasis Therapeutics, Grupo Biotoscana, IQVIA, Matinas BioPharma, Menarini, Mylan, Nabriva Therapeutics, NOXXON Pharma, Octapharma, Paratek Pharmaceuticals, PSI, Roche Diagnostics, Shionogi, Biocon, CoRe Consulting, Molecular Partners, MSGERC, Seres Therapeutics, and Wiley (Blackwell); grants from Janssen, Medicines Company, Melinta Therapeutics, German Research Foundation (DFG), German Federal Ministry of Education and Research, and Immunic, all outside of the submitted work; and a research grant from Scynexis. All other authors declare no competing interests.