Efectividad del aislamiento de contacto frente a las precauciones estándar en el control de la transmisión hospitalaria de Enterobacterias productoras de Beta-lactamasas de Espectro Extendido

La aparición y diseminación de microorganismos resistentes a los antimicrobianos es uno de los principales problemas de Salud Pública en todo el mundo. Dentro de los mecanismos de resistencia antimicrobiana (RAM), uno de los más prevalentes es la producción de betalactamasas de espectro extendido (BLEE), que confieren capacidad para hidrolizar penicilinas, cefalosporinas y aztreonam. Su adquisición está mediada en su mayoría, por plásmidos lo que facilita su diseminación, y su prevalencia ha aumentado de forma espectacular en la comunidad, con un elevado número de portadores intestinales en todo el mundo. Las carbapenemasas (CP) son otro grupo de enzimas, cuya adquisición está mediada en su mayoría por plásmidos; confieren capacidad para hidrolizar los carbapenémicos y, en la mayoría de los casos, resistencia también a los beta-lactámicos, reduciendo enormemente las opciones terapéuticas en caso de infección. Actualmente, se aíslan con mayor frecuencia en centros hospitalarios, habiéndose diseminado por todo el mundo. En los centros sanitarios se realizan diversos tipos de intervenciones con el fin de controlar la transmisión de estos microorganismos, entre ellas se incluyen las precauciones estándar (PE) y las precauciones basadas en la transmisión. Dentro de las precauciones basadas en la transmisión, las precauciones de contacto, más conocidas como aislamiento de contacto (AC), tienen como fin interrumpir la cadena de transmisión de microorganismos que puedan diseminarse por contacto directo o indirecto con el paciente o su entorno. Requiere habitación individual, material clínico de uso exclusivo para el paciente, restricción de visitas y uso de bata y guantes. La aplicación del AC en los pacientes colonizados por enterobacterias productoras de BLEE (E-BLEE) es sin embargo controvertida en muchos casos, y sumamente variable entre países, incluso entre centros del mismo país o región. Se basa en evidencias poco concluyentes y se asocia a efectos indeseables, pudiendo ser un factor contribuyente para el desarrollo de incidentes relacionados con la seguridad del paciente. Supone igualmente un aumento de costes y una disminución de la capacidad de respuesta de hospitalización de aquellos hospitales cuyas habitaciones no son individuales, impidiendo el ingreso de nuevos pacientes como consecuencia del bloqueo de camas. Resumen_ El objetivo principal de esta tesis es evaluar el efecto de las medidas de precaución basadas en la transmisión por contacto (aislamiento de contacto) frente a las precauciones estándar en la transmisión hospitalaria de E-BLEE en pacientes adultos hospitalizados en unidades convencionales (no UCI) con cribado universal al ingreso, durante el Proyecto Europeo RGNOSIS. Se realizó un estudio de intervención aleatorizado con dos brazos, PE y AC, con diseño cruzado antes-después. Entre el 3 de marzo de 2014 y el 3 de abril de 2016, se realizaron cultivos de cribado a todos los pacientes al ingreso o lo antes posible, siempre dentro de los 3 primeros días. Los cultivos se repetían semanalmente mientras el paciente permanecía ingresado y el mismo día del alta si era posible, o en las 48 horas anteriores. Se analizó la diferencia en la densidad de incidencia (DI) de adquisición de E-BLEE entre los dos brazos del estudio a nivel de unidad y hospitalario. En el primer artículo presentado se describe la prevalencia de colonización por E-BLEE al ingreso en unidades de hospitalización con cribado universal en el Hospital Universitario Ramón y Cajal de Madrid. Se contó con la participación de los Servicios de Neumología, Gastroenterología, Urología y Neurocirugía. Se produjeron 12.590 ingresos de 9.706 pacientes; en el 84,55% se obtuvo un frotis rectal dentro de los 3 primeros días del ingreso. La prevalencia de portadores de E-BLEE fue del 7,69% (IC 95% 7,18 – 8,19). El 33,99% de los casos eran portadores conocidos. Se aislaron 843 enterobacterias multirresistentes en 818 pacientes, con 25 pacientes colonizados por dos microorganismos diferentes (0,23%). El 10,44% de las enterobacterias aisladas producían simultáneamente BLEE y CP. Sólo el 0,43% de los pacientes presentaban infección activa por una E-BLEE en el momento del ingreso (69,09% infecciones del tracto urinario). Los microorganismos más frecuentes fueron E. coli BLEE (77,51%), y K. pneumoniae BLEE (20,71%). Se tipó el 24,67% de las BLEE, con un 83,17% de la clase CTX-M (52,88% de CTX-M-15; 12,50% de CTX-M-14). En el caso de las CP, se pudo tipar el 73,86%, con un 90,77% de tipo OXA-48. En el Segundo artículo se evalúa el efecto del AC frente a las PE en la transmisión hospitalaria de E-BLEE en pacientes adultos hospitalizados en 4 hospitales europeos (Hospital Universitario Ramón y Cajal de Madrid; Hospital Universitario de Ginebra, Suiza; Hospital Universitario de Utrecht, Holanda y Hospital Universitario de Berlín, Alemania). Durante el periodo de estudio ingresaron 38.357 pacientes en los servicios participantes. Resumen_ De los 15.184 pacientes con estancia hospitalaria superior a 1 semana, en el 75% (11.368 pacientes) se recogieron al menos 2 cultivos. Se incluyo únicamente a estos pacientes ya que se requerían al menos 2 muestras, la primera negativa, para calificar una E-BLEE como de adquisición hospitalaria. Se monitorizó la adherencia a la higiene de manos y la utilización de batas y guantes, así como el consumo de antimicrobianos, siendo similares en los distintos periodos de estudio. La DI de adquisición hospitalaria de E-BLEE fue de 6‰ días de riesgo (IC 95% 5,4 - 6,7) durante el periodo de AC, y 6,1‰ (IC 95% 5,5 - 6,7) durante el periodo de PE (p=0,9710). Tanto la prevalencia de E-BLEE al ingreso, como la DI de EBLEE fueron similares entre los periodos de AC y PE, a pesar de la variación sustancial entre los diferentes servicios. No se encontró un patrón temporal en la prevalencia el ingreso ni en la adquisición hospitalaria. A nivel de paciente, un modelo multivariante ajustando por la duración de la estancia hospitalaria, servicio, tipo de servicio (médico/quirúrgico) y país, no mostró evidencia de un efecto del AC sobre el riesgo de adquisición de E-BLEE (hazard ratio periodo AC=1,00; IC 95% 0,86-1,15; p=0,8928). En el tercer artículo, se analiza la diversidad de especies y la distribución de las poblaciones de E-BLEE y E-CP a lo largo del periodo de estudio en el Hospital Universitario Ramón y Cajal. La incidencia de portadores de E-BLEE mostró una tendencia descendente durante el periodo de estudio (p=0,003) y no hubo diferencias significativas entre las dos estrategias de control de la transmisión, AC y PE (IRR = 1,04, 95% IC = 0,86–1,25; p = 0,07). Aunque la incidencia de colonización por E-CP también se mostró invariable durante el estudio, (IRR = 1,01, 95% IC = 0,98–1,02; p = 0,41), en uno de los servicios se encontró un aumento estadísticamente significativo al pasar de la estrategia de AC a la de PE, que sería atribuible a un brote de K. penumoniae productora de NDM-1, cuyo posible origen sería un paciente procedente de Pakistán. El microorganismo productor de BLEE más frecuente fue E. coli (78,5%), seguido de K. pneumoniae (17%). La diversidad de especies entre los portadores de E-BLEE permaneció estable a lo largo del tiempo, siendo E. coli la E-BLEE predominante durante todo el estudio. K. pneumoniae (53,5%) fue la especie de E-PC más frecuente, seguida de E. coli (19,2%) y Enterobacter cloacae complex (11,1 %). La diversidad de especies de E-CP disminuyó notablemente a lo largo del estudio, aumentando K. pneumoniae y E. coli y disminuyendo otras especies minoritarias. Resumen_ En conclusión, el aislamiento de contacto de los pacientes colonizados o infectados por EBLEE, en ausencia de brote en unidades de hospitalización convencionales se puede considerar una práctica innecesaria y no recomendable por su falta de efectividad para frenar la transmisión de la RAM, no aportando mejoras a la seguridad de los pacientes. Se deben intensificar los esfuerzos para mejorar el cumplimiento por parte de los profesionales sanitarios de las PE y, en particular, de la higiene de manos, medidas de coste efectividad demostrado en la interrupción de la transmisión de las IRAS, y que no imponen restricciones a los pacientes

Risk analysis for patient safety in surgical departments: Cross-sectional design usefulness

(1) Background: Identifying and measuring adverse events (AE) is a priority for patient safety, which allows us to define and prioritise areas for improvement and evaluate and develop solutions to improve health care quality. The aim of this work was to determine the prevalence of AEs in surgical and medical-surgical departments and to know the health impact of these AEs. (2) Methods: A cross-sectional study determining the prevalence of AEs in surgical and medical-surgical departments was conducted and a comparison was made among both clinical areas. A total of 5228 patients were admitted in 58 hospitals in Argentina, Colombia, Costa Rica, Mexico, and Peru, within the Latin American Study of Adverse Events (IBEAS), led by the Spanish Ministry of Health, the Pan American Health Organization, and the WHO Patient Safety programme. (3) Results: The global prevalence of AEs was 10.7%. However, the prevalence of AEs in surgical departments was 11.9%, while in medical-surgical departments it was 8.9%. The causes of these AEs were associated with surgical procedures (38.6%) and nosocomial infections (35.4%). About 60.6% of the AEs extended hospital stays by 30.7 days on average and 25.8% led to readmission with an average hospitalisation of 15 days. About 22.4% resulted in death, disability, or surgical reintervention. (4) Conclusions: Surgical departments were associated with a higher risk of experiencing AEs

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services

Background: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist’s perception of its quality has not been evaluated. Methods: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of cen‑ tral tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. Results: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfed in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores>70/100 from the frst procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies : a multicenter study in 21 Spanish pulmonology services

Background: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. Methods: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. Results: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. Conclusions: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images

Characterization of carbapenemase-producing Enterobacteriaceae from colonized patients in a university hospital in Madrid, Spain, during the R-GNOSIS project depicts increased clonal diversity over time with maintenance of high-risk clones

Objectives: To describe the incidence and microbiological features of carbapenemase-producing Enterobacteriaceae (CPE) from colonized patients in a Spanish university hospital during a cluster-randomized study [the Resistance of Gram-Negative Organisms: Studying Intervention Strategies (R-GNOSIS) project] on isolation strategies for faecal ESBL carriers. Methods: From March 2014 to March 2016, 15 556 rectal swabs from 8209 patients admitted in two surgical wards and two medical wards were collected and seeded on ESBL and CPE chromogenic agars. Carbapenemase characterization (PCR and sequencing) was performed, and antibiotic susceptibility (MIC), clonality (PFGE and MLST) and diversity (Simpson diversity index estimation) were determined. Results: One hundred and ninety-eight CPE isolates, mainly Klebsiella pneumoniae (53.5%) and Escherichia coli (19.2%), were identified in 162 patients (2%). Prevalence of CPE carriage remained unchanged over time. Overall, amikacin (9.6%), tigecycline (9.6%) and colistin (0.5%) showed low non-susceptibility. The most frequent carbapenemase was OXA-48 (64.1%), followed by VIM-1 (26.8%), NDM-1 (5.3%) and KPC-3 (3.5%), and these were co-produced with ESBLs in 43.9%. OXA-48 plus CTX-M-15 was the most frequent association. Two major K. pneumoniae clones were identified (OXA-48-CTX-M-15-ST11 and VIM-1-SHV-12-ST54) with considerable genetic diversity among the remaining isolates, including OXA-48-E. coli. Species diversity tended to decrease from 0.75 in the first 6 months of the study to 0.43 in the final months. The emergence of new clones (i.e. OXA-48-Kluyvera spp. and NDM-1-K. pneumoniae ST437 and ST101) and displacement of other particular clones were also demonstrated. Conclusions: We describe a polyclonal and changeable CPE population over time. Coexistence of worldwide disseminated clones, such as ST11-OXA-48- K. pneumoniae, with unrelated and emerging OXA-48-E. coli clones, depicts a disturbing CPE epidemiology in our institution

Characterization of carbapenemase-producing Enterobacteriaceae from colonized patients in a university hospital in Madrid, Spain, during the R-GNOSIS project depicts increased clonal diversity over time with maintenance of high-risk clones

Objectives: To describe the incidence and microbiological features of carbapenemase-producing Enterobacteriaceae (CPE) from colonized patients in a Spanish university hospital during a cluster-randomized study [the Resistance of Gram-Negative Organisms: Studying Intervention Strategies (R-GNOSIS) project] on isolation strategies for faecal ESBL carriers. Methods: From March 2014 to March 2016, 15 556 rectal swabs from 8209 patients admitted in two surgical wards and two medical wards were collected and seeded on ESBL and CPE chromogenic agars. Carbapenemase characterization (PCR and sequencing) was performed, and antibiotic susceptibility (MIC), clonality (PFGE and MLST) and diversity (Simpson diversity index estimation) were determined. Results: One hundred and ninety-eight CPE isolates, mainly Klebsiella pneumoniae (53.5%) and Escherichia coli (19.2%), were identified in 162 patients (2%). Prevalence of CPE carriage remained unchanged over time. Overall, amikacin (9.6%), tigecycline (9.6%) and colistin (0.5%) showed low non-susceptibility. The most frequent carbapenemase was OXA-48 (64.1%), followed by VIM-1 (26.8%), NDM-1 (5.3%) and KPC-3 (3.5%), and these were co-produced with ESBLs in 43.9%. OXA-48 plus CTX-M-15 was the most frequent association. Two major K. pneumoniae clones were identified (OXA-48-CTX-M-15-ST11 and VIM-1-SHV-12-ST54) with considerable genetic diversity among the remaining isolates, including OXA-48-E. coli. Species diversity tended to decrease from 0.75 in the first 6 months of the study to 0.43 in the final months. The emergence of new clones (i.e. OXA-48-Kluyvera spp. and NDM-1-K. pneumoniae ST437 and ST101) and displacement of other particular clones were also demonstrated. Conclusions: We describe a polyclonal and changeable CPE population over time. Coexistence of worldwide disseminated clones, such as ST11-OXA-48- K. pneumoniae, with unrelated and emerging OXA-48-E. coli clones, depicts a disturbing CPE epidemiology in our institution

Empleo de vancomicina tópica en la profilaxis de infección de herida de esternotomía: experiencia inicial

Resumen: Introducción: La vancomicina tópica ha demostrado su eficacia para disminuir la incidencia de infección de la herida quirúrgica, sin embargo, su utilidad en cirugía cardiaca permanece en duda. Objetivos: Estudiar el efecto de la vancomicina tópica sobre la incidencia de infección de la herida de esternotomía tras cirugía cardiaca. Material y método: Estudio observacional, retrospectivo, comparando la incidencia de infección de esternotomía entre una cohorte en la que se empleó la profilaxis antibiótica habitual, frente a otra en la que además se asoció vancomicina tópica. Resultados: Se incluyeron un total de 525 pacientes, 47,43% en el grupo tratado con vancomicina. La incidencia global de infección fue significativamente superior en el grupo sin vancomicina (3,6% frente a 10,1%) implicando un riesgo relativo de 2,8 (IC 95% 1,35-5,83; p = 0,004). Las diferencias fueron significativas en la incidencia de infecciones superficial y profunda (p = 0,05), sin alcanzar la significación estadística en la infección órgano-espacio (p = 0,22). El efecto beneficioso de la vancomicina se mantuvo en un modelo de regresión ajustado por los posibles factores de confusión identificados (tabaquismo, reintervención, nefropatía y grado NYHA): odss ratio 3,48 (IC 95% 1,44-8,41; p = 0,006). Los gramnegativos fueron el principal agente causal en el grupo con vancomicina (57,1%) y los grampositivos en el grupo sin vancomicina (66,7%), aunque estas diferencias no alcanzaron la significación estadística. Conclusión: El empleo de vancomicina tópica disminuye la incidencia de infección de la herida de esternotomía, tanto superficial como profunda. Su uso podría producir un cambio en el espectro etiológico de la infección esternal. Abstract: Introduction: Topical vancomycin has demonstrated effectiveness in decreasing the incidence of surgical wound infection; however, its usefulness in cardiac surgery remains in doubt. Objectives: To analyse the effectiveness of topical vancomycin in the reduction of sternal wound infection in cardiac surgery. Material and method: A retrospective observational study was conducted to compare the incidence of sternotomy infection in a cohort in which the usual antibiotic prophylaxis was used, with another cohort in which topical vancomycin was also used. Results: A total of 525 patients were included in the study, with 47.43% in the group treated with vancomycin. The incidence of infection was significantly higher in the group without vancomycin (3.6% versus 10.1%), implying a relative risk of infection of 2.8 (95% CI; 1.35-5.83, p = .0035). The differences were statistically significant as regards the incidence of superficial and deep infections (p = .05), but did not reach statistical significance in organ-space infection (p = .22). The beneficial effect of vancomycin was maintained in a logistic regression model adjusted for possible confounding factors (smoking, re-operation, nephropathy, and NYHA functional grade class): odss ratio 3.48 (95% CI; 1.44-8.41, p = .006). Gramnegative microorganisms were the main causative agent in the vancomycin group (57.1%), whereas it was grampositive in the group without vancomycin (66.70%), although these differences did not reach statistical significance. Conclusion: The use of topical vancomycin decreases the incidence of superficial and deep sternotomy wound infections. Its use could lead to a change in the aetiological spectrum of sternal wound infection. Palabras clave: Infección herida quirúrgica, Vancomicina, Esternotomía media, Profilaxis antibiótica, Antibioterapia tópica, Keywords: Surgical site infection, Vancomycin, Median sternotomy, Antibiotic prophylaxis, Topical antibiotic therap

Cross-sectional versus retrospective cohort design

Background Adverse events (AEs) epidemiology is the first step to improve practice in the healthcare system. Usually, the preferred method used to estimate the magnitude of the problem is the retrospective cohort study design, with retrospective reviews of the medical records. However this data collection involves a sophisticated sampling plan, and a process of intensive review of sometimes very heavy and complex medical records. Cross-sectional survey is also a valid and feasible methodology to study AEs. Objectives The aim of this study is to compare AEs detection using two different methodologies: cross-sectional versus retrospective cohort design. Setting Secondary and tertiary hospitals in five countries: Argentina, Colombia, Costa Rica, Mexico and Peru. Participants The IBEAS Study is a cross-sectional survey with a sample size of 11 379 patients. The retrospective cohort study was obtained from a 10% random sample proportional to hospital size from the entire IBEAS Study population. Methods This study compares the 1-day prevalence of the AEs obtained in the IBEAS Study with the incidence obtained through the retrospective cohort study. Results The prevalence of patients with AEs was 10.47% (95% CI 9.90 to 11.03) (1191/11 379), while the cumulative incidence of the retrospective cohort study was 19.76% (95% CI 17.35% to 22.17%) (215/1088). In both studies the highest risk of suffering AEs was seen in Intensive Care Unit (ICU) patients. Comorbid patients and patients with medical devices showed higher risk. Conclusion The retrospective cohort design, although requires more resources, allows to detect more AEs than the cross-sectional design.publishersversionpublishe

Dissemination routes of the carbapenem resistance plasmid pOXA-48 in a hospital setting

Infections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood. Here, we used mechanistic models combining epidemiological data from more than 9,000 patients with whole genome sequence information from 250 enterobacteria clones to characterise the dissemination routes of the carbapenemase-encoding plasmid pOXA-48 in a hospital setting over a two-year period. Our results revealed frequent between-patient transmission of high-risk pOXA-48-carrying clones, mostly of Klebsiella pneumoniae and sporadically Escherichia coli. The results also identified pOXA-48 dissemination hotspots within the hospital, such as specific wards and individual rooms within wards. Using high-resolution plasmid sequence analysis, we uncovered the pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid transfer occurs in the gut of virtually every colonised patient. The complex and multifaceted epidemiological scenario exposed by this study provides new insights for the development of intervention strategies to control the in-hospital spread of CPE