Improved empirical antibiotic treatment of sepsis after an educational intervention: the ABISS-Edusepsis study.

BACKGROUND: Early appropriate antibiotic treatment is essential in sepsis. We aimed to evaluate the impact of a multifaceted educational intervention to improve antibiotic treatment. We hypothesized that the intervention would hasten and improve the appropriateness of empirical antibiotic administration, favor de-escalation, and decrease mortality. METHODS: We prospectively studied all consecutive patients with sepsis/septic shock admitted to 72 intensive care units (ICUs) throughout Spain in two 4-month periods (before and immediately after the 3-month intervention). We compared process-of-care variables (resuscitation bundle and time-to-initiation, appropriateness, and de-escalation of empirical antibiotic treatment) and outcome variables between the two cohorts. The primary outcome was hospital mortality. We analyzed the intervention's long-term impact in a subset of 50 ICUs. RESULTS: We included 2628 patients (age 64.1 ± 15.2 years; men 64.0%; Acute Physiology and Chronic Health Evaluation (APACHE) II, 22.0 ± 8.1): 1352 in the preintervention cohort and 1276 in the postintervention cohort. In the postintervention cohort, the mean (SD) time from sepsis onset to empirical antibiotic therapy was lower (2.0 (2.7) vs. 2.5 (3.6) h; p = 0.002), the proportion of inappropriate empirical treatments was lower (6.5% vs. 8.9%; p = 0.024), and the proportion of patients in whom antibiotic treatment was de-escalated was higher (20.1% vs. 16.3%; p = 0.004); the expected reduction in mortality did not reach statistical significance (29.4% in the postintervention cohort vs. 30.5% in the preintervention cohort; p = 0.544). Gains observed after the intervention were maintained in the long-term follow-up period. CONCLUSIONS: Despite advances in sepsis treatment, educational interventions can still improve the delivery of care; further improvements might also improve outcomes.

Impact of Source Control in Patients With Severe Sepsis and Septic Shock.

OBJECTIVES: Time to clearance of pathogens is probably critical to outcome in septic shock. Current guidelines recommend intervention for source control within 12 hours after diagnosis. We aimed to determine the epidemiology of source control in the management of sepsis and to analyze the impact of timing to source control on mortality. DESIGN: Prospective observational analysis of the Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter educational intervention to improve antibiotherapy in sepsis. SETTING: Ninety-nine medical-surgical ICUs in Spain. PATIENTS: We enrolled 3,663 patients with severe sepsis or septic shock during three 4-month periods between 2011 and 2013. INTERVENTIONS: Source control and hospital mortality. MEASUREMENTS AND MAIN RESULTS: A total of 1,173 patients (32%) underwent source control, predominantly for abdominal, urinary, and soft-tissue infections. Compared with patients who did not require source control, patients who underwent source control were older, with a greater prevalence of shock, major organ dysfunction, bacteremia, inflammatory markers, and lactic acidemia. In addition, compliance with the resuscitation bundle was worse in those undergoing source control. In patients who underwent source control, crude ICU mortality was lower (21.2% vs 25.1%; p = 0.010); after adjustment for confounding factors, hospital mortality was also lower (odds ratio, 0.809 [95% CI, 0.658-0.994]; p = 0.044). In this observational database analysis, source control after 12 hours was not associated with higher mortality (27.6% vs 26.8%; p = 0.789). CONCLUSIONS: Despite greater severity and worse compliance with resuscitation bundles, mortality was lower in septic patients who underwent source control than in those who did not. The time to source control could not be linked to survival in this observational database.

A review of the factors influencing antimicrobial prescribing.

There are multiple benefits of appropriate antimicrobial prescribing: it has a direct impact on clinical outcomes, avoids adverse effects, is cost effective and, perhaps most importantly, it helps to prevent the emergence of resistance. However, any physician can prescribe antibiotics, which is not the case with other clinically relevant drugs. There is great variability in the prescribing physician's (PP) training, motivation, workload and setting, including accessibility to infectious diseases consultants and/or diagnostic techniques, and therefore there is a high risk of inappropriate prescription. Many antibiotic prescribing errors occur around the selection and duration of treatment. This includes a low threshold for the indication of antibiotics, delayed initiation of treatment when indicated, limited knowledge of local antimicrobial resistance patterns by the PPs, errors in the final choice of dose, route or drug and a lack of de-escalation. Similarly, the prescription of prophylactic antibiotics to prevent surgical site infections, despite being commonly accepted, is suboptimal. Factors that may explain suboptimal use are related to the absence of well-defined protocols, poor knowledge of prophylactic protocols, miscommunication or disagreement between physicians, logistical problems, and a lack of audits. A proper understanding of the prescribing process can guide interventions to improve the PP's practices. Some of the potential interventions included in a stewardship program are education in antimicrobial prescribing, information on the local resistance patterns and accessibility to a qualified infectious diseases consultant.

A review of the factors influencing antimicrobial prescribing / Revisión de los factores que influyen en la prescripción de antibióticos

There are multiple benefits of appropriate antimicrobial prescribing: it has a direct impact on clinical outcomes, avoids adverse effects, is cost effective and, perhaps most importantly, it helps to prevent the emergence of resistance. However, any physician can prescribe antibiotics, which is not the case with other clinically relevant drugs. There is great variability in the prescribing physician's (PP) training, motivation, workload and setting, including accessibility to infectious diseases consultants and/or diagnostic techniques, and therefore there is a high risk of inappropriate prescription. Many antibiotic prescribing errors occur around the selection and duration of treatment. This includes a low threshold for the indication of antibiotics, delayed initiation of treatment when indicated, limited knowledge of local antimicrobial resistance patterns by the PPs, errors in the final choice of dose, route or drug and a lack of de-escalation. Similarly, the prescription of prophylactic antibiotics to prevent surgical site infections, despite being commonly accepted, is suboptimal. Factors that may explain suboptimal use are related to the absence of well-defined protocols, poor knowledge of prophylactic protocols, miscommunication or disagreement between physicians, logistical problems, and a lack of audits. A proper understanding of the prescribing process can guide interventions to improve the PP's practices. Some of the potential interventions included in a stewardship program are education in antimicrobial prescribing, information on the local resistance patterns and accessibility to a qualified infectious diseases consultant

La prescripción adecuada de antimicrobianos tiene un impacto directo sobre la evolución clínica del paciente, evita posibles efectos adversos, es coste-efectiva y contribuye a evitar la emergencia de resistencias. A diferencia de lo que ocurre con otros fármacos de interés clínico, cualquier médico puede prescribirlos. Esto significa que entre los médicos prescriptores (MP) hay una gran variabilidad en el grado de formación, motivación, carga de trabajo y especialidad, la accesibilidad a los consultores de enfermedades infecciosas y/o a técnicas de diagnóstico, lo que conlleva un alto riesgo de uso inadecuado. Muchos de los errores de la prescripción están relacionados con una mala selección o duración de los tratamientos antibióticos. Eso incluye un bajo umbral para la indicación, un retraso en el inicio, un conocimiento limitado de los patrones locales de resistencia, errores en la elección final de dosis, vía o fármaco y, por último, la falta de simplificación de los tratamientos empíricos. Del mismo modo, el uso de antibióticos profilácticos, a pesar de ser comúnmente aceptado, no es óptimo. Las razones fundamentales que explican esta situación están relacionadas con la ausencia de protocolos bien definidos o la falta de conocimiento de estos, la falta de comunicación entre los médicos y/o la existencia de problemas logísticos. Una comprensión adecuada del proceso de prescripción puede guiar las intervenciones para mejorar los hábitos de los MP. Algunas de las posibles intervenciones podrían ser medidas formativas, la difusión de las resistencias locales y la accesibilidad a un consultor experto

Epidemiology, diagnosis and treatment of fungal respiratory infections in the critically ill patient.

OBJECTIVE: To elaborate practical recommendations based on scientific evidence, when available, or on expert opinions for the diagnosis, treatment and prevention of fungal respiratory infections in the critically ill patient, including solid organ transplant recipients. METHODS: Twelve experts from two scientific societies (The Spanish Society for Chemotherapy and The Spanish Society of Intensive Care and Coronary Units) reviewed in a meeting held in March 2012 epidemiological issues and risk factors as basis for a document about prevention, diagnosis and treatment of respiratory fungal infections caused by Candida spp., Aspergillus spp or Zygomycetes. RESULTS: Despite the frequent isolation of Candida spp. from respiratory tract samples, antifungal treatment is not recommended since pneumonia by this fungal species is exceptional in non-neutropenic patients. In the case of Aspergillus spp., approximately 50% isolates from the ICU represent colonization, and the remaining 50% cases are linked to invasive pulmonary aspergillosis (IPA), an infection of high mortality. Main risk factors for invasive disease in the ICU are previous treatment with steroids and chronic obstructive pulmonary disease (COPD). Collection of BAL sample is recommended for culture and galactomannan determination. Voriconazole and liposomal amphotericin B have the indication as primary therapy while caspofungin has the indication as salvage therapy. Although there is no solid data supporting scientific evidence, the group of experts recommends combination therapy in the critically ill patient with sepsis or severe respiratory failure. Zygomycetes cause respiratory infection mainly in neutropenic patients, and liposomal amphotericin B is the elective therapy. CONCLUSIONS: Presence of fungi in respiratory samples from critically ill patients drives to different diagnostic and clinical management approaches. IPA is the most frequent infection and with high mortality.

Value of ß-D-glucan and Candida albicans germ tube antibody for discriminating between Candida colonization and invasive candidiasis in patients with severe abdominal conditions.

PURPOSE: To assess the value of (1→3)-ß-D: -glucan (BDG), Candida albicans germ tube antibody (CAGTA), C-reactive protein (CRP), and procalcitonin (PCT) levels for the diagnosis of invasive candidiasis (IC) and for differentiating Candida spp. colonization from infection in ICU patients with severe abdominal conditions (SAC). METHODS: Prospective study of 176 non-neutropenic patients, with SAC at ICU admission, and expected to stay at least 7 days. Surveillance cultures and BDG, CAGTA, CRP, and PCT levels were performed on the third day of ICU stay and twice a week for four consecutive weeks. Patients were grouped into invasive candidiasis (IC), Candida colonization, and neither colonized/nor infected. The classification and regression tree (CART) analysis was used to predict IC in colonized patients. The discriminatory ability of the obtained prediction rule was assessed by the area under the ROC curve (AUC). RESULTS: The probabilities of IC were 59.3 % for the terminal node of BDG greater than 259 pg/mL and 30.8 % for BDG less than 259 pg/mL and CAGTA positivity, whereas there was a 93.9 % probability in predicting the absence of IC for BDG less than 259 pg/mL and negative CAGTA. Using a cutoff of 30 % for IC probability, the prediction rule showed 90.3 % sensitivity, 54.8 % specificity, 42.4 % positive predictive value, and 93.9 % negative predictive value with an AUC of 0.78 (95 % confidence interval 0.76-0.81). Significant differences in CRP (p = 0.411) and PCT (p = 0.179) among the studied groups were not found. CONCLUSIONS: BDG with a positive test for CAGTA accurately differentiated Candida colonization from IC in patients with SAC, whereas CRP and PCT did not.

Candidemia persistente en una paciente receptora de trasplante renopancreático / Persistent candidemia in a renal-pancreatic transplant patient

El trasplante de órgano sólido ha presentado un aumento en la supervivencia en las últimas décadas en relación con el perfeccionamiento de la técnica quirúrgica, la protocolización del manejo inmu-nosupresor y el uso de profilaxis antimicrobiana. A pesar de ello, la infección fúngica invasiva (IFI) es la mayor causa de morbimortalidad en este grupo de pacientes. En el trasplante renal, la IFI más frecuente es la candidiasis invasiva, que habitualmente se asocia al empleo de nutrición parenteral total, de tratamiento antibiótico de amplio espectro y a la cirugía abdominal. Caso clínico Presentamos el caso de una paciente con trasplante renopancreático reciente que desarrolla una candidemia persistente asociada a catéter, causada por Candida glabrata, que se trata con anidulafungi-na. Presentó una buena evolución clínica y no se observaron interacciones farmacológicas relevantes. Se discuten las posibles causas y las alternativas diagnóstico-terapéuticas de este tipo de infección(AU)

In recent decades, there has been an increase in the survival of recipients of solid organ trans-plants related to the improvement of the surgical technique, the introduction of protocols for immunosu-ppressive therapy, and the use of antimicrobial prophylaxis. Nonetheless, invasive fungal infection (IFI) is currently the major cause of morbidity and mortality in this group of patients. Invasive candidiasis is the most common IFI found after renal transplantation and is usually associated with total parenteral nutrition, broad-spectrum antibiotic therapy and abdominal surgery. Clinical case. We report the case of a recent kidney-pancreas transplant recipient who developed a persis-tent catheter-related candidemia caused by Candida glabrata. The patient was treated with anidulafungin and had a good clinical course with no significant drug interactions. We discuss the possible causes and diagnostic and therapeutic alternatives of this kind of infection(AU)

[Persistent candidemia in a renal-pancreatic transplant patient]. / Candidemia persistente en una paciente receptora de trasplante renopancreático.

BACKGROUND: In recent decades, there has been an increase in the survival of recipients of solid organ transplants related to the improvement of the surgical technique, the introduction of protocols for immunosuppressive therapy, and the use of antimicrobial prophylaxis. Nonetheless, invasive fungal infection (IFI) is currently the major cause of morbidity and mortality in this group of patients. Invasive candidiasis is the most common IFI found after renal transplantation and is usually associated with total parenteral nutrition, broad-spectrum antibiotic therapy and abdominal surgery. CLINICAL CASE: We report the case of a recent kidney-pancreas transplant recipient who developed a persistent catheter-related candidemia caused by Candida glabrata. The patient was treated with anidulafungin and had a good clinical course with no significant drug interactions. We discuss the possible causes and diagnostic and therapeutic alternatives of this kind of infection.

Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH / Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document

Los antimicrobianos son fármacos distintos al resto. Su eficacia en la reducción de la morbilidad y la mortalidad es muy superior a la de otros grupos de medicamentos. Por otra parte, son los únicos fármacos con efectos ecológicos, de manera que su administración puede contribuir a la aparición y diseminación de resistencias microbianas. Finalmente, son utilizados por médicos de prácticamente todas las especialidades. La actual complejidad en el manejo de las enfermedades infecciosas y del aumento de las resistencias hace imprescindible el establecimiento de programas de optimización del uso de antimicrobianos en los hospitales (PROA).Este documento de consenso define los objetivos de los PROA (mejorar los resultados clínicos de los pacientes con infecciones, minimizar los efectos adversos asociados a la utilización de antimicrobianos, incluyendo aquí las resistencias, y garantizar la utilización de tratamientos coste-eficaces) y establece recomendaciones para su implantación en los hospitales españoles. Las líneas maestras de las recomendaciones son: la constitución de un equipo multidisciplinario de antibióticos, dependiente de la Comisión de Infecciones. Los PROA necesitan ser considerados programas institucionales de los hospitales donde se desarrollen. Deben incluir objetivos específicos y resultados cuantificables en función de indicadores, y basarse en la realización de actividades encaminadas a mejorar el uso de antimicrobianos, principalmente mediante actividades formativas y medidas no impositivas de ayuda a la prescripción (AU)

The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures (AU)

[Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document]. / Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH.

The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures.

Actualización sobre infecciones en pacientes de la UCI / Update on infections in ICU patients

Studies carried out in 2006 on severe community-acquiredpneumonia or nosocomial pneumonia requiring admissionto the ICU are numerous and of a high quality. Amongstudies of community-acquired pneumonia, the mostrelevant are those focused on the development andevaluation of systems for the identification of patientswith severe pneumonia, analysis of the impact of theinitial inflammatory response on the course of the disease,and level of adherence to therapeutic guidelines proposedby different scientific societies. Among studiesof nosocomial pneumonia, those involving ventilatorassociatedpneumonia and health care-associatedpneumonia should be emphasized. The reliabilityof different respiratory sampling methods for theetiological diagnosis of pneumonia, the impact of differentetiological agents, and the efficacy of prophylacticmeasures have been the object of different investigations.Important aspects of these studies include the assessmentof different strategies in the use of antimicrobial agentsto decrease the selection of multiresistant pathogens.Moreover, early identification of patients at risk of invasivefungal infections, as well as preemptive treatmentof these infections in selected patients have beentopics of increasing interest(AU)

Los estudios realizados en 2006 sobre la neumoníaextrahospitalaria grave o la neumonía nosocomialque requieren el ingreso en la UCI son numerosos y degran calidad. Entre los trabajos sobre la neumoníaextrahospitalaria, los más relevantes son los que se basanen el desarrollo y la valoración de los sistemas paraidentificar a los pacientes con neumonía grave, en elanálisis del impacto de la respuesta inflamatoria inicialsobre el curso de la enfermedad, y en el nivel deseguimiento de las normas terapéuticas propuestas pordiferentes sociedades científicas. Entre los estudios sobrela neumonía nosocomial, cabe destacar los relacionadoscon la neumonía asociada al respirador o a la asistenciasanitaria. La fiabilidad de los distintos métodos paraobtener muestras respiratorias con el fin de establecerel diagnóstico etiológico, el impacto de los diferentesagentes etiológicos, y la eficacia de las medidasprofilácticas, han sido objeto de diversas investigaciones.Entre los aspectos importantes de estos estudios se hallala valoración de las diferentes estrategias para el usode los agentes antimicrobianos con el fin de reducir laselección de los gérmenes plurirresistentes. Además,la identificación precoz de los pacientes con riesgo deinfecciones micóticas invasivas, así como el tratamientoprecoz de estas infecciones en determinados pacientes,han sido otros tantos temas de interés general(AU)

Update on infections in ICU patients

Los estudios realizados en 2006 sobre la neumoníaextrahospitalaria grave o la neumonía nosocomialque requieren el ingreso en la UCI son numerosos y degran calidad. Entre los trabajos sobre la neumoníaextrahospitalaria, los más relevantes son los que se basan en el desarrollo y la valoración de los sistemas para identificar a los pacientes con neumonía grave, en el análisis del impacto de la respuesta inflamatoria inicial sobre el curso de la enfermedad, y en el nivel deseguimiento de las normas terapéuticas propuestas pordiferentes sociedades científicas. Entre los estudios sobre la neumonía nosocomial, cabe destacar los relacionados con la neumonía asociada al respirador o a la asistencia sanitaria. La fiabilidad de los distintos métodos para obtener muestras respiratorias con el fin de establecer el diagnóstico etiológico, el impacto de los diferentes agentes etiológicos, y la eficacia de las medidas profilácticas, han sido objeto de diversas investigaciones. Entre los aspectos importantes de estos estudios se halla la valoración de las diferentes estrategias para el uso de los agentes antimicrobianos con el fin de reducir la selección de los gérmenes plurirresistentes. Además, la identificación precoz de los pacientes con riesgo de infecciones micóticas invasivas, así como el tratamiento precoz de estas infecciones en determinados pacientes,han sido otros tantos temas de interés general

Studies carried out in 2006 on severe community-acquiredpneumonia or nosocomial pneumonia requiring admissionto the ICU are numerous and of a high quality. Amongstudies of community-acquired pneumonia, the mostrelevant are those focused on the development andevaluation of systems for the identification of patientswith severe pneumonia, analysis of the impact of theinitial inflammatory response on the course of the disease, and level of adherence to therapeutic guidelines proposed by different scientific societies. Among studies of nosocomial pneumonia, those involving ventilatorassociated pneumonia and health care-associatedpneumonia should be emphasized. The reliabilityof different respiratory sampling methods for theetiological diagnosis of pneumonia, the impact of different etiological agents, and the efficacy of prophylactic measures have been the object of different investigations. Important aspects of these studies include the assessment of different strategies in the use of antimicrobial agents to decrease the selection of multiresistant pathogens. Moreover, early identification of patients at risk of invasive fungal infections, as well as preemptive treatment of these infections in selected patients have been topics of increasing interest (AU)

Advances in lower respiratory tract infections in critically ill patients / Avances en las infecciones del tracto respiratorio inferior en los pacientes en situación clínica crítica

The present article is an update of the literature on lower respiratory tract infections in critical patients. A multidisciplinary group of Spanish physicians with expertise in the field selected what they considered to be the most important papers published during 2004 and 2005. Each article was analyzed and discussed by one of the members of the panel. A critical review of all these contributions constitutes the body of this paper. After a review of the state of the art, papers selected in the field of new guidelines, risk factors, new diagnostic methods, antimicrobial therapy, and prevention are discussed

El artículo presente recoge una actualización de la bibliografía médica relativa a las infecciones del tracto respiratorio inferior en los pacientes en situación clínica crítica. Un grupo multidisciplinario de clínicos españoles con experiencia en este área seleccionó los que consideró los artículos más importantes sobre este campo publicados en 2004 y 2005. Cada artículo fue analizado y discutido por uno de los miembros del grupo. El artículo presente recoge una revisión crítica de todas estas contribuciones. Tras una revisión de la situación actual, se comentaron los artículos seleccionados relativos a las nuevas directrices, los factores de riesgo, los nuevos métodos diagnósticos, el tratamiento antimicrobiano y la prevención

Vigilancia de la infección nosocomial en la UCI / Nosocomial infection surveillance in the intensive care unit

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