European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Endothelial Damage and the Microcirculation in Critical Illness.

Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.

Laparoscopic Common Bile Duct Exploration Using a Disposable Bronchoscope.

Laparoscopic common bile duct exploration (LCBDE) remains underutilized in the management of common bile duct (CBD) stones. The exact cause of this under-utilization remains unclear; however, identified barriers to LCBDE implementation include lack of training and unavailability of dedicated instruments. LCBDE is an attractive alternative for stone retrieval in patients with Roux-en-Y gastric bypass given the anatomical difficulty in endoscopic retrograde cholangiopaneatography (ERCP). Direct visualization through choledochoscopy is the method of choice for LCBDE. However, dedicated choledoscopes are expensive and not widely available, which may lead surgeons to seek for alternatives at their particular environment. With the COVID-19 pandemic, disposable bronchoscopes have become widely accessible at our institution, raising the possibility of using one for direct vision of the biliary tract. We present the case of a 61-year-old male with past medical history of Roux-en-Y gastric bypass, who presented to the emergency department with a CBD stone. Successful LCBDE was achieved with the aid of a disposable bronchoscope for direct visualization of the biliary tract. Supplementary Information: The online version contains supplementary material available at 10.1007/s12262-022-03642-7.

New guidelines for hospital-acquired pneumonia/ventilator-associated pneumonia: USA vs. Europe.

PURPOSE OF REVIEW: The International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia were published in 2017 whilst the American guidelines for Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia were launched in 2016 by the Infectious Diseases Society of America/ATS. Both guidelines made updated recommendations based on the most recent evidence sharing not only some parallelisms but also important conceptual differences. RECENT FINDINGS: Contemporary therapy for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) emphasizes the importance of prompt and appropriate antimicrobial therapy. There is an implicit risk, when appropriate means broad spectrum, that liberal use of antimicrobial combinations will encourage the emergence of multidrug resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant bacteria (PDR) and generate untreatable infections, including carbapenemase resistant infections. SUMMARY: American and European guidelines have many areas of common agreement such as limiting antibiotic duration. Both guidelines were in favour of a close clinical assessment. Neither recommended a regular use of biomarkers but only in specific circumstances such as dealing with MDR and treatment failure. Risk factor prediction for MDR differed and whilst American guidelines focus on organ failure, the European ones did it in local ecology and septic shock.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling.

RATIONALE: Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae can invade the myocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia. OBJECTIVES: We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) cause MACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model. METHODS: We examined cardiac tissue from six adult NHPs with severe pneumococcal pneumonia and three uninfected control animals. Three animals were rescued with antibiotics (convalescent animals). Electrocardiographic, echocardiographic, and serum biomarkers of cardiac damage were measured (troponin T, N-terminal pro-brain natriuretic peptide, and heart-type fatty acid binding protein). Histological examination included hematoxylin and eosin staining, immunofluorescence, immunohistochemistry, picrosirius red staining, and transmission electron microscopy. Immunoblots were used to assess the underlying mechanisms. MEASUREMENTS AND MAIN RESULTS: Nonspecific ischemic alterations were detected by electrocardiography and echocardiography. Serum levels of troponin T and heart-type fatty acid binding protein were increased (P < 0.05) after pneumococcal infection in both acutely ill and convalescent NHPs. S. pneumoniae was detected in the myocardium of all NHPs with acute severe pneumonia. Necroptosis and apoptosis were detected in the myocardium of both acutely ill and convalescent NHPs. Evidence of cardiac scar formation was observed only in convalescent animals by transmission electron microscopy and picrosirius red staining. CONCLUSIONS: S. pneumoniae invades the myocardium and induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in an NHP model of severe pneumonia.

EPICO 3.0. Antifungal prophylaxis in solid organ transplant recipients / EPICO 3.0. Profilaxis antifúngica en el paciente trasplantado de órgano sólido

Background. Although over the past decade the management of invasive fungal infection has improved, considerable controversy persists regarding antifungal prophylaxis in solid organ transplant recipients. Aims. To identify the key clinical knowledge and make by consensus the high level recommendations required for antifungal prophylaxis in solid organ transplant recipients. Methods. Spanish prospective questionnaire, which measures consensus through the Delphi technique, was conducted anonymously and by e-mail with 30 national multidisciplinary experts, specialists in invasive fungal infections from six national scientific societies, including intensivists, anesthetists, microbiologists, pharmacologists and specialists in infectious diseases that responded to 12 questions prepared by the coordination group, after an exhaustive review of the literature in the last few years. The level of agreement achieved among experts in each of the categories should be equal to or greater than 70% in order to make a clinical recommendation. In a second term, after extracting the recommendations of the selected topics, a face-to-face meeting was held with more than 60 specialists who were asked to validate the pre-selected recommendations and derived algorithm. Measurements and primary outcomes. Echinocandin antifungal prophylaxis should be considered in liver transplant with major risk factors (retransplantation, renal failure requiring dialysis after transplantation, pretransplant liver failure, not early reoperation, or MELD > 30); heart transplant with hemodialysis, and surgical re-exploration after transplantation; environmental colonization by Aspergillus, or cytomegalovirus (CMV) infection; and pancreas and intestinal transplant in case of acute graft rejection, hemodialysis, initial graft dysfunction, post-perfusion pancreatitis with anastomotic problems or need for laparotomy after transplantation. Antifungal fluconazole prophylaxis should be considered in liver transplant without major risk factors and MELD 20-30, split or living donor, choledochojejunostomy, increased transfusion requirements, renal failure without replacement therapy, early reoperation, or multifocal colonization or infection with Candida; intestinal and pancreas transplant with no risk factors for echinocandin treatment. Liposomal amphotericin B antifungal prophylaxis should be considered in lung transplant (inhalant form) and liver transplant with major risk factors. Antifungal prophylaxis with voriconazole should be considered in lung transplant, and heart transplant with hemodialysis, surgical re-exploration after transplantation, environmental colonization by Aspergillus, or CMV infection. Conclusions. The management of antifungal prophylaxis in solid organ transplant recipients requires the application of knowledge and skills that are detailed in our recommendations and the algorithm developed therein. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their management and improve overall prognosis (AU)

Antecedentes. Aunque en la última década se ha observado una mejora en el tratamiento de la infección fúngica invasiva, todavía existen numerosas controversias en la profilaxis antifúngica del paciente trasplantado de órgano sólido. Objetivos. Identificar los principales conocimientos clínicos y elaborar recomendaciones con un alto nivel de consenso, necesarias para la profilaxis antifúngica del paciente trasplantado de órgano sólido. Métodos. Se realizó un cuestionario prospectivo español, que valora el consenso mediante la técnica Delphi. El cuestionario se llevó a cabo de forma anónima y por correo electrónico con 30 expertos multidisciplinarios nacionales, especialistas en infecciones fúngicas invasivas de seis sociedades científicas nacionales, que incluían intensivistas, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas que respondieron a 12 preguntas preparadas por el grupo de coordinación, tras una revisión exhaustiva de la bibliografía de los últimos años. El nivel de acuerdo alcanzado entre los expertos en cada una de las categorías debía ser igual o superior al 70% para elaborar una recomendación. En un segundo término, después de extraer las recomendaciones de los temas seleccionados, se celebró una reunión presencial con más de 60 especialistas y se les solicitó la validación de las recomendaciones preseleccionadas y del algoritmo derivado de estas. Mediciones y resultados principales. Debe considerarse la profilaxis antifúngica con equinocandinas en el trasplante hepático con los principales factores de riesgo (retrasplante, insuficiencia renal postrasplante con necesidad de diálisis, insuficiencia hepática pretrasplante, reintervención quirúrgica no precoz, o MELD > 30); trasplante cardíaco con hemodiálisis, y reexploración quirúrgica postrasplante; colonización ambiental por Aspergillus, o infección por citomegalovirus; trasplante de páncreas e intestino si existe rechazo agudo del injerto, hemodiálisis, disfunción inicial del injerto, problemas en la anastomosis con pancreatitis posperfusión, o necesidad de laparotomía postrasplante. Debe considerarse la profilaxis antifúngica con fluconazol en el trasplante hepático sin los principales factores de riesgo y MELD de 20-30, split o donante vivo, coledocoyeyunostomía, altos requerimientos transfusionales, fracaso renal sin necesidad de terapia sustitutiva, reintervención precoz o colonización multifocal o infección por Candida, y trasplante de páncreas e intestino sin factores de riesgo para el tratamiento con equinocandina. Debe considerarse la profilaxis antifúngica con anfotericina B liposómica en el trasplante pulmonar (vía inhalada) y el trasplante hepático con los principales factores de riesgo. Debe considerarse la profilaxis antifúngica con voriconazol en el trasplante pulmonar y el trasplante cardíaco con hemodiálisis, reexploración quirúrgica postrasplante, colonización ambiental por Aspergillus o enfermedad por citomegalovirus. Conclusiones. El manejo de la profilaxis antifúngica del paciente trasplantado de órgano sólido requiere la aplicación de los conocimientos y destrezas que se detallan en nuestras recomendaciones y en el algoritmo desarrollado. Estas recomendaciones basadas en la metodología Delphi pueden ayudar a identificar a los potenciales pacientes, estandarizar su tratamiento en conjunto y mejorar su pronóstico (AU)

EPICO 3.0. Recommendations on invasive candidiasis in patients with complicated intra-abdominal infection and surgical patients with ICU extended stay / EPICO 3.0. Recomendaciones para el manejo de la candidiasis invasiva en pacientes críticos con infección intraabdominal complicada y pacientes quirúrgicos de larga estancia en la UCI

Background. Although in the last decade the management of invasive fungal infections has improved, a number of controversies persist regarding the management of complicated intra-abdominal infection and surgical extended length-of-stay (LOS) patients in intensive care unit (ICU). Aims. To identify the essential clinical knowledge and elaborate a set of recommendations, with a high level of consensus, necessary for the management of postsurgical patients with complicated intra-abdominal infection and surgical patients with ICU extended stay. Methods. A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all of them specialists in fungal invasive infections from six scientific national societies; these experts were intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They answered 11 questions drafted by the coordination group after conducting a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each should be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting which was held after extracting recommendations from the chosen topics and in which they validated the pre-selected recommendations and derived algorithm. Results. After the second Delphi round, the following 11 recommendations with high degree of consensus were validated. For «surgical patients» seven recommendations were validated: (1) risk factors for invasive candidiasis (IC), (2) usefulness of blood culture and direct examination of abdominal fluid to start empirical treatment; (3) PCR for treatment discontinuation; (4) start antifungal treatment in patients with anastomotic leaks; (5) usefulness of Candida score (CS) but not (6) the Dupont score for initiating antifungal therapy in the event of anastomotic leakage or tertiary peritonitis, and (7) the administration of echinocandins as first line treatment in this special population. For «surgical ICU extended LOS patients» four recommendations were validated: (1) risk factors for IC, (2) presence of multi-colonization by Candida as a required variable of the CS, (3) starting antifungal treatment with CS≥4, and (4) to perform non-culture-based microbiological techniques in stable septic patients without evident focus. Conclusions. The diagnosis and management of IC in ICU surgical patients requires the application of a broad range of knowledge and skills that we summarize in our recommendations. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their global management and improve their outcomes (AU)

Antecedentes. Aunque en la última década se ha observado un mejor control de la infección fúngica invasiva, todavía existen numerosas controversias en el manejo del paciente posquirúrgico con infección intraabdominal complicada y del paciente quirúrgico de larga estancia en UCI. Objetivos. Identificar los principales conocimientos clínicos necesarios y elaborar recomendaciones con un alto nivel de consenso para el tratamiento del paciente posquirúrgico con infección intraabdominal complicada y del paciente quirúrgico de larga estancia en UCI. Métodos. Se realizó un cuestionario español prospectivo que mide el grado de consenso mediante la técnica Delphi. Dicho cuestionario fue realizado de forma anónima y por correo electrónico por 30 expertos multidisciplinarios nacionales, especialistas en infecciones fúngicas invasivas, de 6 sociedades científicas nacionales. Los expertos incluían intensivistas, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas que respondieron a 11 preguntas preparadas por el grupo de coordinación, preguntas que fueron confeccionadas tras una revisión exhaustiva de la literatura de los últimos años. El grado de acuerdo alcanzado entre los expertos en cada una de las categorías debía ser igual o superior al 70% para redactar una recomendación. En un segundo término, después de extraer las recomendaciones de los temas seleccionados, se celebró una reunión presencial con 73 especialistas y se les solicitó la validación de las recomendaciones preseleccionadas y de los algoritmos derivados de estas. Resultados. Concluida la segunda ronda se validaron 11 recomendaciones con un elevado grado de consenso. Para los pacientes con infección intraabdominal complicada se validaron 7 recomendaciones: 1) factores de riesgo para la candidiasis invasiva; 2) utilidad del hemocultivo y del examen directo del líquido abdominal para iniciar tratamiento empírico; 3) PCR para la discontinuación del tratamiento; 4) inicio de tratamiento antifúngico en pacientes con dehiscencia de sutura anastomótica; 5) utilidad del Candida Score; 6) no utilidad de la escala de Dupont para el inicio de tratamiento antifúngico en caso de dehiscencia de sutura anastomótica o peritonitis terciaria, y 7) administración de equinocandinas como primera opción de tratamiento para esta población específica. Para los pacientes quirúrgicos de larga estancia en la UCI se validaron 4 recomendaciones: 1) factores de riesgo para candidiasis invasiva; 2) presencia de multicolonización por Candida como variable requerida del Candida Score; 3) inicio de tratamiento antifúngico si Candida Score≥4, y 4) determinación de técnicas microbiológicas no basadas en el cultivo en el paciente estable con sepsis sin foco evidente. Conclusiones. El diagnóstico y abordaje de la candidiasis invasiva en los pacientes quirúrgicos en UCI requiere de la aplicación del amplio conocimiento y habilidades establecidas en nuestras recomendaciones. Estas recomendaciones, basadas en la metodología Delphi, pueden ayudar a identificar a los potenciales pacientes, estandarizar su manejo en conjunto y mejorar sus resultados clínicos (AU)

EPICO 3.0. Empirical antifungal therapy in critically-ill hematology patients / EPICO 3.0. Tratamiento antifúngico empírico en pacientes hematológicos en estado crítico

Background. Although in the past decade the management of invasive fungal infections has improved, a number of controversies persist regarding empirical antifungal treatment in critically-ill hematology patients. Aims. To identify key clinical knowledge to elaborate a set of recommendations, with a high level of consensus, necessary for the approach to fungal infections in critically-ill hematology patients. Methods. A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists in fungal invasive infections from six scientific national societies; intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They responded to 10 questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category must be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. Results. Assess administering antifungal treatment to patients with high/medium risk factors and fever for over 4 days after onset of antibiotic therapy, and in the event of negative galactomannan or if no detection analysis has been performed and no relevant findings in the sinus and chest computed tomography (CT) have been detected, (1) in the case the patient did not receive prophylaxis, or was administered fluconazole, caspofungin treatment is recommended; (2) in the event the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B is recommended and caspofungin as second choice therapy; (3) in the event that the prophylaxis received was an echinocandin, liposomal amphotericin B therapy is recommended and voriconazole as second choice. Assess administering antifungal treatment in patients with high/medium risk factors and fever for more than 4 days after onset of antibiotic therapy, and in the event of a positive galactomannan and/or sinus and chest CT suggests fungal infection caused by filamentous fungi, (1) in the event the patient did not receive antifungal prophylaxis or was administered fluconazole, the recommended treatment of choice is voriconazole or liposomal amphotericin B; (2) if the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B with caspofungin is recommended and monotherapy with liposomal amphotericin B or the combination of voriconazole and anidulafungin are recommended as second choice therapies; (3) in the event an echinocandin was administered as prophylaxis, liposomal amphotericin B or voriconazole are the recommended treatments of choice. Consider the administration of antifungal treatment in patients with high/medium risk factors and fever for more than 4 days after onset of antibiotic therapy, and in the event of a negative galactomannan and the sinus and chest CT suggests fungal infection caused by filamentous fungi, (1) if the patient did not receive prophylaxis or was administered fluconazole, the recommended treatment of choice is liposomal amphotericin B or voriconazole; (2) in the case the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B is recommended as first choice therapy and liposomal amphotericin B combined with caspofungin as second choice; (3) in the event an echinocandin was administered as prophylaxis, liposomal amphotericin B or voriconazole are the recommended treatments of choice. Conclusions. The empirical antifungal approach in critically-ill hematology patients requires the application of the broad range of knowledge and skills described in our recommendations and algorithm. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their management and improve overall prognosis (AU)

Antecedentes. Aunque en la última década se ha observado una mejora en el tratamiento de la micosis invasiva, todavía existen numerosas controversias en el tratamiento antifúngico empírico del paciente hematológico en estado crítico. Objetivos. Identificar los principales conocimientos clínicos y elaborar recomendaciones con un alto grado de consenso, necesarias para el abordaje de la micosis invasiva en el paciente hematológico en estado crítico. Métodos. Se ha empleado un cuestionario prospectivo español, que mide el consenso mediante la técnica Delphi. Se llevó a cabo de forma anónima y por correo electrónico con 30 expertos multidisciplinarios nacionales, especialistas en micosis invasivas de seis sociedades científicas nacionales, incluyendo intensivistas, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas, los cuales respondieron a 10 preguntas preparadas por el grupo de coordinación, tras una revisión exhaustiva de la bibliografía de los últimos años. El grado de acuerdo alcanzado entre los expertos en cada una de las categorías debería ser igual o superior al 70% para ser seleccionada. En una segunda fase, después de extraer las recomendaciones de los temas seleccionados, se celebró una reunión presencial con 73 especialistas y se les solicitó la validación de las recomendaciones preseleccionadas y del algoritmo derivado de estas. Resultados. Se evalúa la administración de tratamiento antifúngico en pacientes hematológicos con factores de riesgo alto/medio y fiebre de más de 4 días después del inicio del tratamiento antibiótico si el galactomanano es negativo o no se ha realizado, y la TC de senos y tórax no aporta datos relevantes: 1) si no recibían profilaxis o era con fluconazol, se recomienda realizar un tratamiento con caspofungina; 2) en caso de que el paciente reciba profilaxis con un azol con actividad contra hongos filamentosos, la recomendación es la utilización de anfotericina B liposómica y como segunda opción, caspofungina, o 3) en el supuesto de que la profilaxis que reciba sea una equinocandina, la recomendación de tratamiento sería la anfotericina B liposómica y como alternativa el voriconazol. En pacientes con factores de riesgo alto/medio y fiebre de más de 4 días después del inicio del tratamiento antibiótico, si el galactomanano es positivo y/o la TC de senos y tórax sugiere infección por hongos filamentosos: 1) si el paciente no recibe profilaxis o es esta es con fluconazol, la recomendación es utilizar como tratamiento voriconazol o anfotericina B liposómica; 2) si la profilaxis que recibe es con un azol con acción contra hongos filamentosos, la recomendación es la utilización de anfotericina B liposómica con caspofungina y como alternativa anfotericina B liposómica en monoterapia o la combinación voriconazol con anidulafungina, o 3) si la profilaxis es con una equinocandina, la recomendación de tratamiento es emplear anfotericina B liposómica o voriconazol. En pacientes con factores de riesgo alto/medio y fiebre de más de 4 días después del inicio del tratamiento antibiótico, si el galactomanano es negativo y la TC de senos y tórax sugiere infección por hongos filamentosos: 1) si el paciente no recibe profilaxis o es con fluconazol, la recomendación es utilizar como tratamiento anfotericina B liposómica o voriconazol; 2) si la profilaxis que recibe es con un azol con acción contra hongos filamentosos, la recomendación es utilizar anfotericina B liposómica y como alternativa anfotericina B liposómica combinada con caspofungina, o 3) si la profilaxis es con una equinocandina, la recomendación de tratamiento es anfotericina B liposómica o voriconazol. Conclusiones. El abordaje del tratamiento antifúngico empírico del paciente crítico hematológico requiere la aplicación de los conocimientos y destrezas que se detallan en nuestras recomendaciones y en el algoritmo desarrollado. Estas recomendaciones basadas en la metodología Delphi pueden ayudar a identificar a los potenciales pacientes, estandarizar su tratamiento en conjunto y mejorar su pronóstico (AU)

EPICO 3.0. Management of non-neutropenic patients in medical wards / EPICO 3.0. Tratamiento del paciente no neutropénico en la planta de medicina interna

Background. Although the management of invasive fungal infection (IFI) has improved, a number of controversies persist regarding the approach to invasive fungal infection in non-neutropenic medical ward patients. Aims. To identify the essential clinical knowledge to elaborate a set of recommendations with a high level of consensus necessary for the management of IFI in non-neutropenic medical ward patients. Methods. A prospective, Spanish questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists (intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases) in IFI and belonging to six scientific national societies. They responded to five questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category had to be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. Results. The following recommendations were validated and included in the algorithm: 1. several elements were identified as risk factors for invasive candidiasis (IC) in non-hematologic medical patients; 2. no agreement on the use of the colonization index to decide whether prescribing an early antifungal treatment to stable patients (no shock), with sepsis and no other evident focus and IC risk factors; 3. agreement on the use of the Candida Score to decide whether prescribing early antifungal treatment to stable patients (no shock) with sepsis and no other evident focus and IC risk factors; 4. agreement on initiating early antifungal treatment in stable patients (no shock) with a colonization index>0.4, sepsis with no other evident focus and IC risk factors; 5. agreement on the performance of additional procedures in stable patients (no shock) with sepsis and no other evident focus, IC risk factors, without colonization index>0.4, but with a high degree of suspicion. Conclusions. Based on the expert's recommendations, an algorithm for the management of non-neutropenic medical patients was constructed and validated. This algorithm may be useful to support bedside prescription (AU)

Antecedentes. A pesar de que el manejo de la micosis invasiva ha mejorado, persisten ciertas controversias en su tratamiento en pacientes no neutropénicos. Objetivos. Identificar el conocimiento clínico esencial y elaborar, con un alto nivel de consenso, las recomendaciones necesarias para el manejo de la micosis invasiva en pacientes no neutropénicos. Métodos. Treinta expertos multidisciplinarios españoles en micosis invasiva (intensivistas, anestesistas, microbiólogos, farmacólogos y especialistas en enfermedades infecciosas) pertenecientes a 6 sociedades científicas contestaron anónimamente un cuestionario que evaluaba el grado de consenso mediante la técnica Delphi. Los expertos respondieron a 5 preguntas elaboradas por los coordinadores después de una revisión exhaustiva de la bibligorafía reciente. El grado de acuerdo necesario para seleccionar una categoría fue igual o superior al 70%. Posteriormente, 73 especialistas asistieron a una reunión en que se extrajeron las recomendaciones que se utilizaron en la elaboración de un algoritmo para la ayuda en la toma de una decisión clínica. Resultados. Las recomendaciones validadas e incluidas en el algoritmo fueron las siguientes: 1) varias situaciones se definieron como factores de riesgo para la candidiasis invasiva (CI) en pacientes no hematológicos; 2) no hubo acuerdo sobre el uso del índice de colonización para decidir la prescripción de tratamiento antifúngico precoz en pacientes estables (sin shock) con septicemia, sin foco evidente y con factores de riesgo para CI; 3) hubo acuerdo en el uso del Candida Score para decidir la prescripción de tratamiento antifúngico precoz en pacientes estables (sin shock) con septicemia, sin foco evidente y con factores de riesgo para CI; 4) hubo acuerdo en el inicio de tratamiento antifúngico precoz en pacientes estables (sin shock) con sepsis, sin foco evidente e índice de colonización >0,4 y con factores de riesgo para CI; 5) hubo acuerdo para realizar los procedimientos diagnósticos adicionales en pacientes estables (sin shock) con septicemia, sin foco evidente, factores de riesgo para CI e índice de colonización <0,4, pero con alto índice de sospecha. Conclusiones. Se ha elaborado un algoritmo de manejo de la CI en pacientes no neutropénicos basado en las recomendaciones de expertos. Este algoritmo puede ser útil como soporte a la prescripción a pie de cama (AU)

Endothelial adhesion molecules and multiple organ failure in patients with severe sepsis.

OBJECTIVE: To determine if serum levels of endothelial adhesion molecules were associated with the development of multiple organ failure (MOF) and in-hospital mortality in adult patients with severe sepsis. DESIGN: This study was a secondary data analysis of a prospective cohort study. SETTING: Patients were admitted to two tertiary intensive care units in San Antonio, TX, between 2007 and 2012. PATIENTS: Patients with severe sepsis at the time of intensive care unit (ICU) admission were enrolled. Inclusion criteria were consistent with previously published criteria for severe sepsis or septic shock in adults. Exclusion criteria included immunosuppressive medications or conditions. INTERVENTIONS: None. MEASUREMENTS: Baseline serum levels of the following endothelial cell adhesion molecules were measured within the first 72h of ICU admission: Intracellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Vascular Endothelial Growth Factor (VEGF). The primary and secondary outcomes were development of MOF (⩾2 organ dysfunction) and in-hospital mortality, respectively. MAIN RESULTS: Forty-eight patients were enrolled in this study, of which 29 (60%) developed MOF. Patients that developed MOF had higher levels of VCAM-1 (p=0.01) and ICAM-1 (p=0.01), but not VEGF (p=0.70) compared with patients without MOF (single organ failure only). The area under the curve (AUC) to predict MOF according to VCAM-1, ICAM-1 and VEGF was 0.71, 0.73, and 0.54, respectively. Only increased VCAM-1 levels were associated with in-hospital mortality (p=0.03). These associations were maintained even after adjusting for APACHE and SOFA scores using logistic regression. CONCLUSIONS: High levels of serum ICAM-1 was associated with the development of MOF. High levels of VCAM-1 was associated with both MOF and in-hospital mortality.

EPICO 3.0. Empirical antifungal therapy in critically-ill hematology patients.

BACKGROUND: Although in the past decade the management of invasive fungal infections has improved, a number of controversies persist regarding empirical antifungal treatment in critically-ill hematology patients. AIMS: To identify key clinical knowledge to elaborate a set of recommendations, with a high level of consensus, necessary for the approach to fungal infections in critically-ill hematology patients. METHODS: A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists in fungal invasive infections from six scientific national societies; intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They responded to 10 questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category must be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. RESULTS: Assess administering antifungal treatment to patients with high/medium risk factors and fever for over 4 days after onset of antibiotic therapy, and in the event of negative galactomannan or if no detection analysis has been performed and no relevant findings in the sinus and chest computed tomography (CT) have been detected, (1) in the case the patient did not receive prophylaxis, or was administered fluconazole, caspofungin treatment is recommended; (2) in the event the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B is recommended and caspofungin as second choice therapy; (3) in the event that the prophylaxis received was an echinocandin, liposomal amphotericin B therapy is recommended and voriconazole as second choice. Assess administering antifungal treatment in patients with high/medium risk factors and fever for more than 4 days after onset of antibiotic therapy, and in the event of a positive galactomannan and/or sinus and chest CT suggests fungal infection caused by filamentous fungi, (1) in the event the patient did not receive antifungal prophylaxis or was administered fluconazole, the recommended treatment of choice is voriconazole or liposomal amphotericin B; (2) if the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B with caspofungin is recommended and monotherapy with liposomal amphotericin B or the combination of voriconazole and anidulafungin are recommended as second choice therapies; (3) in the event an echinocandin was administered as prophylaxis, liposomal amphotericin B or voriconazole are the recommended treatments of choice. Consider the administration of antifungal treatment in patients with high/medium risk factors and fever for more than 4 days after onset of antibiotic therapy, and in the event of a negative galactomannan and the sinus and chest CT suggests fungal infection caused by filamentous fungi, (1) if the patient did not receive prophylaxis or was administered fluconazole, the recommended treatment of choice is liposomal amphotericin B or voriconazole; (2) in the case the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B is recommended as first choice therapy and liposomal amphotericin B combined with caspofungin as second choice; (3) in the event an echinocandin was administered as prophylaxis, liposomal amphotericin B or voriconazole are the recommended treatments of choice. CONCLUSIONS: The empirical antifungal approach in critically-ill hematology patients requires the application of the broad range of knowledge and skills described in our recommendations and algorithm. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their management and improve overall prognosis.

EPICO 3.0. Management of non-neutropenic patients in medical wards.

BACKGROUND: Although the management of invasive fungal infection (IFI) has improved, a number of controversies persist regarding the approach to invasive fungal infection in non-neutropenic medical ward patients. AIMS: To identify the essential clinical knowledge to elaborate a set of recommendations with a high level of consensus necessary for the management of IFI in non-neutropenic medical ward patients. METHODS: A prospective, Spanish questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists (intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases) in IFI and belonging to six scientific national societies. They responded to five questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category had to be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. RESULTS: The following recommendations were validated and included in the algorithm: 1. several elements were identified as risk factors for invasive candidiasis (IC) in non-hematologic medical patients; 2. no agreement on the use of the colonization index to decide whether prescribing an early antifungal treatment to stable patients (no shock), with sepsis and no other evident focus and IC risk factors; 3. agreement on the use of the Candida Score to decide whether prescribing early antifungal treatment to stable patients (no shock) with sepsis and no other evident focus and IC risk factors; 4. agreement on initiating early antifungal treatment in stable patients (no shock) with a colonization index>0.4, sepsis with no other evident focus and IC risk factors; 5. agreement on the performance of additional procedures in stable patients (no shock) with sepsis and no other evident focus, IC risk factors, without colonization index>0.4, but with a high degree of suspicion. CONCLUSIONS: Based on the expert's recommendations, an algorithm for the management of non-neutropenic medical patients was constructed and validated. This algorithm may be useful to support bedside prescription.

Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study.

BACKGROUND: Antibiotic resistance is a major global health problem and pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) have become of particular concern in the management of lower respiratory tract infections. However, few data are available on the worldwide prevalence and risk factors for MRSA pneumonia. We aimed to determine the point prevalence of MRSA pneumonia and identify specific MRSA risk factors in community-dwelling patients hospitalised with pneumonia. METHODS: We did an international, multicentre study of community-dwelling, adult patients admitted to hospital with pneumonia who had microbiological tests taken within 24 h of presentation. We recruited investigators from 222 hospitals in 54 countries to gather point-prevalence data for all patients admitted with these characteristics during 4 days randomly selected during the months of March, April, May, and June in 2015. We assessed prevalence of MRSA pneumonia and associated risk factors through logistic regression analysis. FINDINGS: 3702 patients hospitalised with pneumonia were enrolled, with 3193 patients receiving microbiological tests within 24 h of admission, forming the patient population. 1173 (37%) had at least one pathogen isolated (culture-positive population). The overall prevalence of confirmed MRSA pneumonia was 3·0% (n=95), with differing prevalence between continents and countries. Three risk factors were independently associated with MRSA pneumonia: previous MRSA infection or colonisation (odds ratio 6·21, 95% CI 3·25-11·85), recurrent skin infections (2·87, 1·10-7·45), and severe pneumonia disease (2·39, 1·55-3·68). INTERPRETATION: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia. FUNDING: None.

EPICO 3.0. Recommendations on invasive candidiasis in patients with complicated intra-abdominal infection and surgical patients with ICU extended stay.

BACKGROUND: Although in the last decade the management of invasive fungal infections has improved, a number of controversies persist regarding the management of complicated intra-abdominal infection and surgical extended length-of-stay (LOS) patients in intensive care unit (ICU). AIMS: To identify the essential clinical knowledge and elaborate a set of recommendations, with a high level of consensus, necessary for the management of postsurgical patients with complicated intra-abdominal infection and surgical patients with ICU extended stay. METHODS: A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all of them specialists in fungal invasive infections from six scientific national societies; these experts were intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They answered 11 questions drafted by the coordination group after conducting a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each should be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting which was held after extracting recommendations from the chosen topics and in which they validated the pre-selected recommendations and derived algorithm. RESULTS: After the second Delphi round, the following 11 recommendations with high degree of consensus were validated. For "surgical patients" seven recommendations were validated: (1) risk factors for invasive candidiasis (IC), (2) usefulness of blood culture and direct examination of abdominal fluid to start empirical treatment; (3) PCR for treatment discontinuation; (4) start antifungal treatment in patients with anastomotic leaks; (5) usefulness of Candida score (CS) but not (6) the Dupont score for initiating antifungal therapy in the event of anastomotic leakage or tertiary peritonitis, and (7) the administration of echinocandins as first line treatment in this special population. For "surgical ICU extended LOS patients" four recommendations were validated: (1) risk factors for IC, (2) presence of multi-colonization by Candida as a required variable of the CS, (3) starting antifungal treatment with CS≥4, and (4) to perform non-culture-based microbiological techniques in stable septic patients without evident focus. CONCLUSIONS: The diagnosis and management of IC in ICU surgical patients requires the application of a broad range of knowledge and skills that we summarize in our recommendations. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their global management and improve their outcomes.