Impact of Aspergillus spp. isolation in the first 24 hours of admission in critically ill patients with severe influenza virus pneumonia / Impacto del aislamiento de Aspergillus spp. en las primeras 24h de ingreso en pacientes críticos con neumonía grave por el virus influenza

Objective To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. Design Secondary analysis of an observational and prospective cohort study. Setting ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. Patients Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. Interventions None. Main variables of interest Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. Results 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92–10.04); HIV (OR 3.83, 95% CI 1.08–13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99–11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95–3.51), immunosuppression (OR 2.05 95% CI 1.46–2.88) and AI (OR 3.24, 95% CI 1.60–6.53) were variables independently associated with ICU mortality. Conclusions Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented (AU)

Objetivo Determinar la incidencia y el impacto sobre la mortalidad del aislamiento de Aspergillus spp. (AI) en paciente críticos con neumonía por influenza en las primeras 24h de ingreso. Diseño Análisis secundario de estudio de cohortes observacional y prospectivo. Ámbito Unidades de cuidados intensivos (UCI) participantes de forma voluntaria en el registro español de neumonía por influenza grave, desde junio de 2009 hasta junio de 2019. Pacientes Pacientes consecutivos con diagnóstico de neumonía grave por influenza, confirmado por prueba de reacción en cadena de la polimerasa. Intervenciones Ninguna. Variables principales Incidencia de AI. Variables demográficas, comorbilidades, necesidad de ventilación mecánica y presencia de shock al ingreso. APACHE II. Resultados Se analizaron 3.702 pacientes. La incidencia de AI fue del 1,13% (n=42). Las neoplasias hematológicas (OR: 4,39; IC 95%: 1,92-10,04); VIH (OR: 3,83; IC 95%: 1,08-13,63) y otras situaciones de inmunosupresión (OR: 4,87; IC 95%: 1,99-11,87) fueron variables que se asociaron de forma independiente con AI. El árbol de decisión de CHAID mostró que la variable neoplasias hematológicas era la más relacionada con la variable Aspergillus spp. con una incidencia del 3,3%. Neoplasias hematológicas (OR: 2,62; IC 95%: 1,95-3,51), inmunosupresión (OR: 2,05; IC 95%: 1,46-2,88) y AI (OR: 3,24; IC 95%: 1,60-6,53) se asociaron de forma independiente con mayor mortalidad en la UCI. Conclusiones El tratamiento antifúngico empírico en nuestra población estaría justificado en los pacientes con inmunosupresión. En los pacientes con riesgo moderado-grave, la búsqueda activa de Aspergillus spp. debería implementarse (AU)

Impact of Aspergillus spp. isolation in the first 24 hours of admission in critically ill patients with severe influenza virus pneumonia.

OBJECTIVE: To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24h of admission. DESIGN: Secondary analysis of an observational and prospective cohort study. SETTING: ICUs voluntary participating in the Spanish severe Influenza pneumonia registry, between June 2009 and June 2019. PATIENTS: Consecutive patients admitted to the ICU with diagnosis of severe influenza pneumonia, confirmed by real-time polymerase chain reaction. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Incidence of AI in respiratory samples. Demographic variables, comorbidities, need for mechanical ventilation and the presence of shock according at admission. Acute Physiology and Chronic Health Evaluation II (APACHE II) scale calculated on ICU admission. RESULTS: 3702 patients were analyzed in this study. AI incidence was 1.13% (n=42). Hematological malignancies (OR 4.39, 95% CI 1.92-10.04); HIV (OR 3.83, 95% CI 1.08-13.63), and other immunosuppression situations (OR 4.87, 95% CI 1.99-11.87) were factors independently associated with the presence of Aspergillus spp. The automatic CHAID decision tree showed that hematologic disease with an incidence of 3.3% was the most closely AI related variable. Hematological disease (OR 2.62 95% CI 1.95-3.51), immunosuppression (OR 2.05 95% CI 1.46-2.88) and AI (OR 3.24, 95% CI 1.60-6.53) were variables independently associated with ICU mortality. CONCLUSIONS: Empirical antifungal treatment in our population may only be justified in immunocompromised patients. In moderate-high risk cases, active search for Aspergillus spp. should be implemented.

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Current aspects in sepsis approach. Turning things around.

The incidence and prevalence of sepsis depend on the definitions and records that we use and we may be underestimating their impact. Up to 60% of the cases come from the community and in 30-60% we obtain microbiological information. Sometimes its presentation is ambiguous and there may be a delay in its detection, especially in the fragile population. Procalcitonin is the most validated biomarker for bacterial sepsis and the one that best discriminates the non-infectious cause. Presepsin and pro-adrenomedullin are useful for early diagnosis, risk stratification and prognosis in septic patients. The combination of biomarkers is even more useful to clarify an infectious cause than any isolated biomarker. Resuscitation with artificial colloids has worse results than crystalloids, especially in patients with renal insufficiency. The combination of saline solution and balanced crystalloids is associated with a better prognosis. Albumin is only recommended in patients who require a large volume of fluids. The modern molecular methods on the direct sample or the identification by MALDI-TOF on positive blood culture have helped to shorten the response times in diagnosis, to optimize the antibiotic treatment and to facilitate stewardship programs. The hemodynamic response in neonates and children is different from that in adults. In neonatal sepsis, persistent pulmonary hypertension leads to an increase in right ventricular afterload and heart failure with hepatomegaly. Hypotension, poor cardiac output with elevated systemic vascular resistance (cold shock) is often a terminal sign in septic shock. Developing ultra-fast Point-of-Care tests (less than 30 minutes), implementing technologies based on omics, big data or massive sequencing or restoring "healthy" microbiomes in critical patients after treatment are the main focuses of research in sepsis. The main benefits of establishing a sepsis code are to decrease the time to achieve diagnosis and treatment, improve organization, unify criteria, promote teamwork to achieve common goals, increase participation, motivation and satisfaction among team members, and reduce costs.

Anidulafungin for the treatment of candidaemia/invasive candidiasis in selected critically ill patients.

A prospective, multicentre, phase IIIb study with an exploratory, open-label design was conducted to evaluate efficacy and safety of anidulafungin for the treatment of candidaemia/invasive candidiasis (C/IC) in specific ICU patient populations. Adult ICU patients with confirmed C/IC meeting ≥ 1 of the following criteria were enrolled: post-abdominal surgery, solid tumour, renal/hepatic insufficiency, solid organ transplant, neutropaenia, and age ≥ 65 years. Patients received anidulafungin (200 mg on day 1, 100 mg/day thereafter) for 10-42 days, optionally followed by oral voriconazole/fluconazole. The primary efficacy endpoint was global (clinical and microbiological) response at the end of all therapy (EOT). Secondary endpoints included global response at the end of intravenous therapy (EOIVT) and at 2 and 6 weeks post-EOT, survival at day 90, and incidence of adverse events (AEs). The primary efficacy analysis was performed in the modified intent-to-treat (MITT) population, excluding unknown/missing responses. The safety and MITT populations consisted of 216 and 170 patients, respectively. The most common pathogens were Candida albicans (55.9%), C. glabrata (14.7%) and C. parapsilosis (10.0%). Global success was 69.5% (107/154; 95% CI, 61.6-76.6) at EOT, 70.7% (111/157) at EOIVT, 60.2% (77/128) at 2 weeks post-EOT, and 50.5% (55/109) at 6 weeks post-EOT. When unknown/missing responses were included as failures, the respective success rates were 62.9%, 65.3%, 45.3% and 32.4%. Survival at day 90 was 53.8%. Treatment-related AEs occurred in 33/216 (15.3%) patients, four (1.9%) of whom had serious AEs. Anidulafungin was effective, safe and well tolerated for the treatment of C/IC in selected groups of ICU patients.

[Up-date on the treatment of serious fungal infections]. / Actualización sobre el tratamiento de las infecciones fúngicas graves.

INTRODUCTION: In recent years, there has been an exponential increase in the incidence of severe fungal infections with elevated morbidity-mortality. An attempt is currently being made to obtain faster and more reliable diagnostic tests for a certainty diagnosis and to be able to use clinical criteria to identify patients who could be candidates to receive early antifungal treatment and thus be able to improve the prognosis. SOURCES: For the purposes of this article, we reviewed the indexed literature for the last 15 years. We used different key words: invasive fungal infection (IFI), invasive aspergillosis, candidemia, and candidiasis, emerging fungi, prophylaxis and antifungal treatment (empiric, directed and pre-emptive treatment). DEVELOPMENT: The approach to antifungal treatment is also undergoing significant changes. These go from the appearance of new molecules, new generations of other already known ones and also changes in the more <> approach in its use. This article is structured on the use slope of antifungal agents in non-neutropenic critical patients from their prophylaxis, empiric treatment, aimed towards new strategies (pre-emptive treatment or early therapy or combined use of antifungal agents). Furthermore, an attempt is being made to obtain simple scores to indicate their early onset in patients with high risk of IFI. CONCLUSIONS: The combination of rapid identification of patients with risk (scores), faster diagnostic methods and finally more effective antifungal treatment with the providing of new antifungal agents and/or strategies will be essential to try to decrease the elevated morbidity-mortality in severe patients.

Actualización sobre el tratamiento de las infecciones fúngicas graves / Up-date on the treatment of serious fungal infections

Introducción. En los últimos años hay un incrementoexponencial en la incidencia de las infecciones fúngicasgraves con una elevada morbimortalidad. En la actualidadse está intentando obtener pruebas diagnósticas más rápidasy fiables para el diagnóstico de certeza y poder identificarcon criterios clínicos a los pacientes potencialmente candidatospara recibir precozmente un tratamiento antifúngicoy así poder mejorar el pronóstico.Fuentes. Para la realización de este artículo hemos realizadouna revisión basada en la bibliografía indexada en losúltimos 15 años. Hemos utilizado diferentes palabras clave:infección fúngica invasora (IFI), candidemia, candidiasis yaspergilosis invasora, hongos emergentes, profilaxis y tratamiento(empírico, dirigido y preemptive treatment) antifúngico.Desarrollo. El planteamiento del tratamiento antifúngicotambién está presentando cambios significativos. Éstosvan desde la aparición de nuevas moléculas hasta nuevasgeneraciones de otras ya conocidas y también cambios en elplanteamiento más «tradicional» en su uso. Este artículo seestructura en las vertientes del uso de antifúngicos en pacientescríticos no neutropénicos desde su profilaxis y tratamientoempírico dirigido hasta nuevas estrategias (preemptivetreatment o terapia anticipada o el uso combinado deantifúngicos). Además se busca conseguir puntuacionessencillas para indicar su inicio precoz en pacientes con elevadoriesgo de IFI.Conclusiones. La combinación de rápida identificaciónde enfermos con riesgo (puntuaciones), métodos diagnósticosmás rápidos y finalmente un tratamiento antifúngicomás eficaz con el aporte de nuevos antifúngicos y/o estrategias serán clave para intentar disminuir la elevada morbimortalidaden pacientes graves (AU)

Introduction. In recent years, there has been an exponentialincrease in the incidence of severe fungal infectionswith elevated morbidity-mortality. An attempt is currentlybeing made to obtain faster and more reliable diagnostictests for a certainty diagnosis and to be able to use clinicalcriteria to identify patients who could be candidates to receiveearly antifungal treatment and thus be able to improvethe prognosis.Sources. For the purposes of this article, we reviewedthe indexed literature for the last 15 years. We used differentkey words: invasive fungal infection (IFI), invasive aspergillosis,candidemia, and candidiasis, emerging fungi,prophylaxis and antifungal treatment (empiric, directed andpre-emptive treatment).Development. The approach to antifungal treatment isalso undergoing significant changes. These go from the appearanceof new molecules, new generations of other alreadyknown ones and also changes in the more «traditional»approach in its use. This article is structured on the use slopeof antifungal agents in non-neutropenic critical patientsfrom their prophylaxis, empiric treatment, aimed towardsnew strategies (pre-emptive treatment or early therapy orcombined use of antifungal agents). Furthermore, an attemptis being made to obtain simple scores to indicate theirearly onset in patients with high risk of IFI.Conclusions. The combination of rapid identification ofpatients with risk (scores), faster diagnostic methods and finally more effective antifungal treatment with the providingof new antifungal agents and/or strategies will be essentialto try to decrease the elevated morbidity-mortality insevere patients (AU)

Levofloxacino en el tratamiento de infecciones nosocomiales en pacientes críticos / Levofloxacin in the treatment of nosocomial infection in critically ill patients

Introducción. El levofloxacino (LVX) es uno de los antibióticosmás utilizados en pacientes críticos ingresados enServicios o Unidades de Cuidados Intensivos (UCI) españolas.Su utilización en infecciones comunitarias está ampliamentedocumentada, mientras que su uso en infecciones nosocomiales(IN) es menos frecuente y conocido.Objetivo. Describir las indicaciones y formas de empleode LVX en el tratamiento de IN en pacientes ingresados enUCI españolas.Material y método. Estudio abierto, retrospectivo, observacionaly multicéntrico. Se han incluido todos los pacientesingresados en UCI que en los años 2004-2005 recibieron LVXpara el tratamiento de IN. Se ha cumplimentado un cuadernode recogida de datos (CRD) que incluye variables demográficas,de la infección, del tratamiento y de la evolución del proceso infeccioso y del paciente. Se describe la utilizaciónde LVX dependiendo de la IN. Se realiza análisis de regresión logística para identificar las variables relacionadas con respuesta satisfactoria. Los resultados se expresan mediante laodds ratio (OR) y el intervalo de confianza (IC) del 95%.Resultados. Se han incluido 949 pacientes en 87 UCIque han recibido LVX para el tratamiento de 1.103 IN: 460(41,7%) neumonías no relacionadas con ventilación mecánica,256 (23,2%) neumonías relacionadas con ventilación mecánica,107 (9,7%) bacteriemias primarias o relacionadas con catéteresvasculares, 47 (4,3%) infecciones urinarias relacionadascon sonda uretral, 42 (3,8%) infecciones quirúrgicas profundaso de órgano-espacio y 191 (17,3 %) otras infecciones.APACHE II al ingreso de 19,6 (desviación estándar [DE]: 8) yrespuesta sistémica de sepsis grave o shock séptico en el 50,4% de los casos. En 776 (82,7%) ocasiones se ha iniciado el tratamiento de forma empírica y en 589 (62,1%) casos la dosisde elección ha sido de 0,5 g/12 h, con una duración media de 9 días (AU)

Introduction. Levofloxacin (LVX) is one of the most frequentlyused antibiotics in critical patients admitted to SpanishIntensive Care Units (ICU). Their use in communityacquiredinfections has been widely documented, while it is less frequent and known in nosocomial infections (NI).Objective. To describe the indications and utilizationpatterns of LVX in the treatment of NI in patients admittedto Spanish ICU.Material and methods. Open-label, retrospective, observational and multicenter study. All patients admittedto ICU and who were being treated for NI with LVX in the years 2004-2005 were included. A case reportform (CRF) was drawn up and included demographic, infection, treatment, infectious process and patient development variables. NI-dependent LVX usage was described.A logistical regression analysis was carried out in order to identify the variables associated with a satisfactoryresponse. Results are expressed by means of the odds ratio and a 95% confidence interval.Results. A total of 949 patients who were given LVXfor the treatment of 1,103 NI were recruited in 87 ICU:460 (41.7%) with non-mechanical ventilation associatedpneumonia, 256 (23.2 %) mechanical-ventilation associatedpneumonia, 107 (9.7 %) with primary or vascularcatheter-related bacteremia, 47 (4.3 %) with urethral catheter-related urinary infections, 42 (3.8%) with organspaceor deep surgical infections and 191 (17.3%) whohad other types of infection. An APACHE II upon admissionof 19.6 (SD: 8) and severe sepsis or septic shocksystemic response in 50.4% of all cases. On 776 (82.7%)occasions treatment was initiated on an empirical basisand in 589 (62.1%) cases the dose of choice was of 0.5 g/12 h, with a mean duration of 9 days (AU)

[Levofloxacin in the treatment of nosocomial infection in critically ill patients]. / Levofloxacino en el tratamiento de infecciones nosocomiales en pacientes críticos.

INTRODUCTION: Levofloxacin (LVX) is one of the most frequently used antibiotics in critical patients admitted to Spanish Intensive Care Units (ICU). Their use in community-acquired infections has been widely documented, while it is less frequent and known in nosocomial infections (NI). OBJECTIVE: To describe the indications and utilization patterns of LVX in the treatment of NI in patients admitted to Spanish ICU. MATERIAL AND METHODS: Open-label, retrospective, observational and multicenter study. All patients admitted to ICU and who were being treated for NI with LVX in the years 2004-2005 were included. A case report form (CRF) was drawn up and included demographic, infection, treatment, infectious process and patient development variables. NI-dependent LVX usage was described. A logistical regression analysis was carried out in order to identify the variables associated with a satisfactory response. Results are expressed by means of the odds ratio and a 95% confidence interval. RESULTS: A total of 949 patients who were given LVX for the treatment of 1,103 NI were recruited in 87 ICU: 460 (41.7%) with non-mechanical ventilation associated pneumonia, 256 (23.2 %) mechanical-ventilation associated pneumonia, 107 (9.7 %) with primary or vascular catheter-related bacteremia, 47 (4.3 %) with urethral catheter-related urinary infections, 42 (3.8%) with organspace or deep surgical infections and 191 (17.3%) who had other types of infection. An APACHE II upon admission of 19.6 (SD: 8) and severe sepsis or septic shock systemic response in 50.4% of all cases. On 776 (82.7%) occasions treatment was initiated on an empirical basis and in 589 (62.1%) cases the dose of choice was of 0.5 g/ 12 h, with a mean duration of 9 days. In 738 (77.8 %) patients, LVX was used in association with other antibiotics. The clinical response by treatment end was rated as satisfactory in 67.4 % of all NI. Factors related to a non-satisfactory response were as follows: APACHE II (OR: 1.05; 95% CI: 1.028-1.078); septic shock (OR: 2.62; 95 % CI: 1.623-4.219); the requirement for changes in treatment due to poor clinical progress (OR: 66.67; 95% CI: 15.384-250), the presence of non-covered microorganisms (OR: 6.58; 95% CI: 3.663-11.765), the appearance of new resistant pathogens (OR: 6.94; 95 % CI: 2.445- 19.608) or the diagnosis of a new infection (OR: 3.68; 95% CI: 1.504-8.929); solid neoplasm (OR: 1.98; 95% CI: 1.156-3.899); chronic liver disease (OR: 3.11; 95 % CI: 1.429-8.475) and the absence of etiology confirmation (OR: 2.39; 95 % CI: 1.624-3.510). One or more adverse events which were possibly or probably related to the use of LVX were detected in 104 (11.0%) patients. Total intra-ICU mortality amounted to 26.1%, while the accumulated in-hospital mortality was 33.8%. CONCLUSIONS: LVX is a common therapeutic option in the treatment of nosocomial infections in critical patients. It is predominantly used in an empirical manner, at a dose of 0.5 g every 12 hours and in combination with other antibiotics.

[Clinical presentations of nosocomial aspergillosis]. / Presentaciones clínicas de la aspergilosis nosocomial.

Aspergillus is a very ubiquitous fungal in our environment, including hospitals, being the second in frequency in colonization and infection, just after Candida spp. Aspergillus nosocomial infections have increased, because the number of immunocompromised patients has also increased. Nosocomial infections can be caused by different species of Aspergillus, being pulmonary manifestations the most frequent. Primary or secondary nonpulmonary infections can affect the brain, heart, kidney, eyes and other organs. The mortality due to invasive aspergillosis is very high, and a clinical-radiological suspicion and, specially the instauration of a rapid treatment with high doses of amphotericin B or its new formulations (associated with surgery in many times) may modify the mortality observed in this patients.