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Byline: Benoit P. Guery (1), Maiken C. Arendrup (2), Georg Auzinger (3), Elie Azoulay (4), Marcio Borges Sa (5), Elizabeth M. Johnson (6), Eckhard Muller (7), Christian Putensen (8), Coleman Rotstein (9), Gabriele Sganga (10), Mario Venditti (11), Rafael Zaragoza Crespo (12), Bart Jan Kullberg (13) Keywords: Antifungal; Azole; Candida; Candidiasis; Echinocandins; Invasive candidiasis; Intensive care; Polyenes Abstract: Background Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU). Objective and methods To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion. Results and conclusions Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized with fluconazole resistant strains or there has been recent past exposure to an azole ( Author Affiliation: (1) Infectious Diseases, SGRIVI, Hopital Huriez, CHRU Lille, 59045, Lille Cedex, France (2) Unit of Mycology, Department Bacteriology, Mycology and Parasitology, Statens Serum Institut, Building 43/117, 2300, Copenhagen, Denmark (3) Liver Intensive Care, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK (4) Service de Reanimation Medicale, Hopital Saint-Louis, 1, avenue Claude-Bellefaux, 75010, Paris, France (5) Sepsis Unit, Intensive Care Department, Hospital Son Llatzer, Palma de Mallorca, Spain (6) Mycology Reference Laboratory, National Collection of Pathogenic Fungi, The HPA Centre for Infections, HPA South West Laboratory, Myrtle Road, Kingsdown, Bristol, BS2 8EL, UK (7) Universitatsklinik fur Anasthesiologie, Intensivmedizin und Schmerztherapie, Knappschaftskrankenhaus Bochum, Langendreer, Klinikum der Ruhr-Universitat, In der Schornau 23--25, 44892, Bochum, Germany (8) Operative Intensivmedizin, Klinik und Poliklinik fur Anasthesiologie und Operative Intensivmedizin, Rheinische-Friedrich-Wilhelms Universitat Bonn, Sigmund-Freud Str. 25, 53127, Bonn, Germany (9) Division of Infectious Diseases, University Health Network, Toronto General Hospital, NCSB 11-1212, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada (10) Department of Surgery, Division of General Surgery and Organ Transplantation, Policlinico 'A Gemelli', Catholic University, Largo Gemelli, 8, 00168, Rome, Italy (11) Internal Medicine, Clinical Medicine Department, 'La Sapienza' University, Rome, Viale dell' Universita, 37, 00185, Rome, Italy (12) Secretario GTEI-SEMICYUC, Medicina Intensiva, Hospital Universitario Dr. Peset, Avenida Gaspa Aguilar, 90, 46107, Valencia, Spain (13) Department of Medicine (463), Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands Article History: Registration Date: 10/10/2008 Received Date: 09/10/2008 Accepted Date: 09/10/2008 Online Date: 30/10/2008 Article note: Part I is published at: doi: 10.1007/s00134-008-1338-7. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1339-6) contains supplementary material, which is available to authorized users.

Byline: Benoit P. Guery (1), Maiken C. Arendrup (2), Georg Auzinger (3), Elie Azoulay (4), Marcio Borges Sa (5), Elizabeth M. Johnson (6), Eckhard Muller (7), Christian Putensen (8), Coleman Rotstein (9), Gabriele Sganga (10), Mario Venditti (11), Rafael Zaragoza Crespo (12), Bart Jan Kullberg (13) Keywords: Antifungal; Azole; Candida; Candidiasis; Echinocandins; Invasive candidiasis; Intensive care; Polyenes Abstract: Background Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU). Objectives and methods To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and a European expert panel discussion. Results and conclusions Candida albicans remains the most frequently isolated fungal species followed by C. glabrata. The diagnosis of invasive candidiasis involves both clinical and laboratory parameters, but neither of these are specific. One of the main features in diagnosis is the evaluation of risk factor for infection which will identify patients in need of pre-emptive or empiric treatment. Clinical scores were built from those risk factors. Among laboratory diagnosis, a positive blood culture from a normally sterile site provides positive evidence. Surrogate markers have also been proposed like 1,3 [beta]-d glucan level, mannans, or PCR testing. Invasive candidiasis and candidemia is a growing concern in the ICU, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific. The diagnosis remains difficult and is usually based on the evaluation of risk factors. Author Affiliation: (1) Infectious Diseases, SGRIVI, Hopital Huriez, CHRU Lille, 59045, Lille Cedex, France (2) Unit of Mycology, Department of Bacteriology, Mycology and Parasitology, Statens Serum Institut, Building 43/117, 2300, Copenhagen, Denmark (3) Liver Intensive Care, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK (4) Service de Reanimation Medicale, Hopital Saint-Louis, 1, Avenue Claude-Bellefaux, 75010, Paris, France (5) Sepsis Unit, Intensive Care Department, Hospital Son Llatzer, Palma de Mallorca, Spain (6) Mycology Reference Laboratory, National Collection of Pathogenic Fungi, The HPA Centre for Infections, HPA South West Laboratory, Myrtle Road, Kingsdown, Bristol, BS2 8EL, UK (7) Universitatsklinik fur Anasthesiologie, Intensivmedizin und Schmerztherapie, Knappschaftskrankenhaus Bochum, Langendreer, Klinikum der Ruhr, Universitat, In der Schornau 23-25, 44892, Bochum, Germany (8) Operative Intensivmedizin, Klinik und Poliklinik fur Anasthesiologie und Operative Intensivmedizin, Rheinische-Friedrich-Wilhelms Universitat Bonn, Sigmund-Freud Str. 25, 53127, Bonn, Germany (9) Division of Infectious Diseases, University Health Network, Toronto General Hospital, NCSB 11-1212, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada (10) Division of General Surgery and Organ Transplantation, Policlinico 'A Gemelli', Department of Surgery, Catholic University, Largo Gemelli, 8, 00168, Rome, Italy (11) Internal Medicine, Clinical Medicine Department, 'La Sapienza' University, Rome, Viale dell' Universita, 37, 00185, Rome, Italy (12) Secretario GTEI-SEMICYUC, Medicina Intensiva Hospital Universitario Dr. Peset, Avenida Gaspa Aguilar, 90, 46107, Valencia, Spain (13) Department of Medicine (463), Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands Article History: Registration Date: 10/10/2008 Received Date: 22/04/2008 Accepted Date: 05/10/2008 Online Date: 30/10/2008 Article note: Part II is published at: doi: 10.1007/s00134-008-1339-6.

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Background : Bacterial/fungal coinfections (COIs) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay, and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections upon ICU admission. Methods : We conducted a secondary analysis of two prospective multicenter cohort studies with confirmed influenza A (H1N1)pdm09 and COVID-19. Multiple logistic regression (MLR) and random forest (RF) were used to identify factors associated with BFC in the overall population and in each subgroup (influenza and COVID-19). The performance of these models was assessed by the area under the ROC curve (AUC) and out-of-bag (OOB) methods for MLR and RF, respectively. Results : Of the 8902 patients, 41.6% had influenza and 58.4% had SARS-CoV-2 infection. The median age was 60 years, 66% were male, and the crude ICU mortality was 25%. BFC was observed in 14.2% of patients. Overall, the predictive models showed modest performances, with an AUC of 0.68 (MLR) and OOB 36.9% (RF). Specific models did not show improved performance. However, age, procalcitonin, CRP, APACHE II, SOFA, and shock were factors associated with BFC in most models. Conclusions : Machine learning models do not adequately predict the presence of co-infection in critically ill patients with pandemic virus infection. However, the presence of factors such as advanced age, elevated procalcitonin or CPR, and high severity of illness should alert clinicians to the need to rule out this complication on admission to the ICU.

Objectives: Antibiotic treatment is vital in patients with severe sepsis/septic shock. The objectives were to assess the degree of concordance between antibiotic prescribed in emergencies and post requirements; to relate it to health outcomes (mortality) and to analyze the reasons for disagreement., Material and Methods: Retrospective descriptive study of antibiotic treatment prescribed in emergencies and the subsequent treatment in patients with criteria of severe sepsis/septic shock in 2013. We collected patient demographic characteristics, infectious focus, antibiotic prescribed from emergencies and subsequent changes. It was considered concordant if there were no changes, if there were changes, but the initial antibiotic was right and suspensions for end of treatment. Mortality and evolution were analyzed., Results: Six hundred patients were included. A 60% experienced changes respect to the antibiotic treatment initiated in emergencies (87.6% justified), with a degree of overall antibiotic concordance of 47.5% The mortality rate at end-point was 9.83%, with no statistically significant relationship with the degree of concordance (OR=0.864 (0.503-1.484)/χ2=0.28; p=0.597). Reasons for change of antibiotic: clinical outcome (17.96%), change of spectrum (35.03%), de-escalation (41.32%), sequential therapy (8.68%). An 11% required ICU admission. Clinical outcomes: resolution of the disease (79.2%), readmission after 30 days (7.7%) and transfer to health centers (4.5%). The median hospital stay was 7 days., Conclusions: The degree of concordance antibiotic was quite high, and the mortality rate was lower than that described in the literature, without relating to the discordance. The presence of concordance was associated with fewer readmissions and ICU admissions. The main reasons for disagreement were inadequate spectrum selection and change after microbiological crops.

Introduction: Blood culture contaminations can lead to unnecessary diagnostic procedures and treatments, increasing workload, length of stay, and costs., Objetives: Development of an educational program to reduce contamination rates., Material and Methods: Our study compared contamination rates (CR) between a pre-intervention period (Ppre) and post-intervention period (Ppos), where clinical charts from patients with positive blood cultures were reviewed. Intervention consisted of a questionnaire where knowledge of blood culture practice and its significance was assessed. Results are discussed and explained., Results: A presentation on blood culture guidelines was discussed in every nurse station. There was a median of 64% (40.8-78.5) attendance rate. The median of correct answers was 69% in the Ppre (54.1-83.3) with 85.7% (83.3-100) in the Ppos, indicating an improvement in 85.7% of the departments that could be compared. There were 136 (4.2%) contaminants in the Ppre and 186 (6.05%) in the Ppos (P=.005). Among the different departments the average of CR varied from 5% vs 7.5% (P=.79) between 2011 and 2012. Only 2 departments reduced CR by 2% to 2.5%, the difference was not significant., Conclusions: The intervention failed to reduce overall contamination rates, but knowledge of blood culture practice improved. Our results identified the errors that will help us to design a successful approach in future follow-up programs., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)