Impact of the “Zero Resistance” program on acquisition of multidrug-resistant bacteria in patients admitted to Intensive Care Units in Spain. A prospective, intervention, multimodal, multicenter study / Impacto del Proyecto “Resistencia Zero” en la adquisición de bacterias multirresistentes en pacientes ingresados en Unidades de Cuidados Intensivos en España. Estudio de intervención, multimodal y multicéntrico

Objective To assess the impact of a multimodal interventional project (“Zero Resistance”) on the acquisition of multidrug-resistant bacteria (MDR-B) during the patient’s ICU stay. Design Prospective, open-label, interventional, multicenter study. Setting 103 ICUs. Patients Critically ill patients admitted to the ICUs over a 27-month period. Interventions Implementation of a bundle of 10 recommendations to prevent emergence and spread of MDR-B in the ICU. Main variable of interest Rate of patients acquiring MDR-B during their ICU stay, with differentiation between colonization and infection. Results A total of 139,505 patients were included. In 5409 (3.9%) patients, 6020 MDR-B on ICU admission were identified, and in 3648 (2.6%) patients, 4269 new MDR-B during ICU stay were isolated. The rate of patients with MDR-B detected on admission increased significantly (IRR 1.43, 95% CI 1.31–1.56) (p<0.001) during the study period, with an increase of 32.2% between the initial and final monthly rates. On the contrary, the rate of patients with MDR-B during ICU stay decreased non-significantly (IRR 0.93, 95% CI 0.83–1.03) (p=0.174), with a 24.9% decrease between initial and final monthly rates. According to the classification into colonization or infection, there was a highly significant increase of MDR-B colonizations detected on admission (IRR 1.69, 95% CI 1.52–1.83; p<0.0001) and a very significant decrease of MDR-B-infections during ICU stay (IRR 0.67, 95% CI 0.57–0.80, p<0.0001). Conclusions The implementation of ZR project-recommendations was associated with a significantly reduction an infection produced by MDR-B acquired during the patient’s ICU stay (AU)

Objetivo Evaluar el impacto de un proyecto de intervención multimodal (“Resistencia Zero”, RZ) en la adquisición de bacterias multirresistentes (BMR) durante la estancia en UCI. Diseño Estudio prospectivo, abierto, intervencionista, multicéntrico. Ámbito 103 UCI. Pacientes Pacientes críticos ingresados en UCI, durante un período de 27 meses. Intervenciones Implementación de un paquete de 10 recomendaciones para prevenir la aparición y propagación de BMR en UCI. Principal variable de interés Tasa de pacientes que adquieren BMR durante su estancia en UCI, diferenciando entre colonización e infección. Resultados Se incluyeron 139.505 pacientes. En 5.409(3,9%), se identificaron 6.020 BMR al ingreso y en 3.648(2,6%), se aislaron 4.269 nuevas BMR durante la estancia en UCI. La tasa de pacientes con BMR detectadas al ingreso aumentó significativamente (IRR 1,43, IC 95% 1,31–1,56) (p<0,001) durante el periodo de estudio, con un incremento del 32,2% entre las tasas mensuales inicial y final. Por el contrario, la tasa de pacientes con BMR detectadas durante la estancia en UCI disminuyó, no significativamente (IRR 0,93, IC 95% 0,83–1,03) (p=0,174), con una disminución del 24,9% entre las tasas mensuales iniciales y finales. Según la clasificación en colonización o infección, hubo un aumento significativo de colonizaciones por BMR detectadas al ingreso (IR 1,69, IC 95% 1,52–1,83; p<0,0001) y una disminución significativa de infecciones producidas por BMR adquiridas durante la estancia en UCI (IR 0,67, IC 95% 0,57–0,80, p<0,0001). Conclusiones La implementación de las recomendaciones del proyecto RZ se asoció con una reducción significativa de pacientes con infecciones por BMR adquiridas en UCI (AU)

Impact of the "Zero Resistance" program on acquisition of multidrug-resistant bacteria in patients admitted to Intensive Care Units in Spain. A prospective, intervention, multimodal, multicenter study.

OBJECTIVE: To assess the impact of a multimodal interventional project ("Zero Resistance") on the acquisition of multidrug-resistant bacteria (MDR-B) during the patient's ICU stay. DESIGN: Prospective, open-label, interventional, multicenter study. SETTING: 103 ICUs. PATIENTS: Critically ill patients admitted to the ICUs over a 27-month period. INTERVENTIONS: Implementation of a bundle of 10 recommendations to prevent emergence and spread of MDR-B in the ICU. MAIN VARIABLE OF INTEREST: Rate of patients acquiring MDR-B during their ICU stay, with differentiation between colonization and infection. RESULTS: A total of 139,505 patients were included. In 5409 (3.9%) patients, 6020 MDR-B on ICU admission were identified, and in 3648 (2.6%) patients, 4269 new MDR-B during ICU stay were isolated. The rate of patients with MDR-B detected on admission increased significantly (IRR 1.43, 95% CI 1.31-1.56) (p<0.001) during the study period, with an increase of 32.2% between the initial and final monthly rates. On the contrary, the rate of patients with MDR-B during ICU stay decreased non-significantly (IRR 0.93, 95% CI 0.83-1.03) (p=0.174), with a 24.9% decrease between initial and final monthly rates. According to the classification into colonization or infection, there was a highly significant increase of MDR-B colonizations detected on admission (IRR 1.69, 95% CI 1.52-1.83; p<0.0001) and a very significant decrease of MDR-B-infections during ICU stay (IRR 0.67, 95% CI 0.57-0.80, p<0.0001). CONCLUSIONS: The implementation of ZR project-recommendations was associated with a significantly reduction an infection produced by MDR-B acquired during the patient's ICU stay.

Study of risk factors for healthcare-associated infections in acute cardiac patients using categorical principal component analysis (CATPCA).

Using categorical principal component analysis, we aimed to determine the relationship between health care-associated infections (HAIs) and diagnostic categories (DCs) in patients with acute heart disease using data collected in the Spanish prospective ENVIN-HELICS intensive care registry over a 10-year period (2005-2015). A total of 69,876 admissions were included, of which 5597 developed HAIs. Two 2-component CATPCA models were developed. In the first model, all cases were included; the first component was determined by the duration of the invasive devices, the ICU stay, the APACHE II score and the HAIs; the second component was determined by the type of admission (medical or surgical) and by the DCs. No clear association between DCs and HAIs was found. Cronbach's alpha was 0.899, and the variance accounted for (VAF) was 52.5%. The second model included only admissions that developed HAIs; the first component was determined by the duration of the invasive devices and the ICU stay; the second component was determined by the inflammatory response, the mortality in the ICU and the HAIs. Cronbach's alpha value was 0.855, and VAF was 46.9%. These findings highlight the role of exposure to invasive devices in the development of HAIS in patients with acute heart disease.

Usefulness of therapeutic drug monitoring of piperacillin and meropenem in routine clinical practice: a prospective cohort study in critically ill patients.

Background: Beta-lactam anti-infective levels after standard dosing have been shown to be subtherapeutic when renal clearance is augmented. Objective: To determine if piperacillin and meropenem are found to be in their therapeutic range in infected critically ill patients when administered by continuous intravenous infusion (CII) assisted by a therapeutic drug monitoring (TDM) report issued by the pharmacy service. Methods: This prospective non-controlled intervention study evaluated septic patients in an intensive care unit. Patients received a loading dose of meropenem or piperacillin-tazobactam and the antibiotics were afterwards administered by CII. Blood concentrations were determined by high-performance liquid chromatography assays. The adequacy of ß-lactam therapy in the cohort subjected to intervention was assessed by determining whether plasma levels during CII were >4 times the informed minimum inhibitory concentration during the first 96 hours of treatment. Results: A total of 124 patients were subject to TDM during antibiotic treatment but, for the analysis of the fulfilment of pharmacodynamic requirements, data from 31/124 (25%) were excluded. Of the whole cohort of treatment courses, 57/93 (61.3%) reached the target level. Plasma levels were adequate in 41/70 (58.6%) and 16/23 (69.6%) of the patients treated with piperacillin-tazobactam and meropenem, respectively. Globally, recommendations based on TDM results were followed in 35/93 (37.6%) of the treatment courses. Conclusions: The results of the study show that, in critically ill patients with sepsis, there is a significant proportion of treatment courses where target levels are not reached even if the antibiotics are administered by CII and TDM support is provided by the pharmacy service. This TDM support should be offered on a real-time basis to be really useful.

Dificultades en el cumplimiento de recomendaciones para prevenir las complicaciones asociadas a dispositivos de acceso vascular / Difficulties in the implementation of recommendations to prevent the complications associated with vascular access devices

OBJETIVO: conocer las dificultades en el cumplimiento de las recomendaciones según la Care Bundle para prevenir las complicaciones asociadas a dispositivos de acceso vascular y valorar los factores asociados a las dificultades identificadas. MÉTODO: estudio transversal descriptivo. La población de estudio fueron médicos y enfermeras del Hospital Universitario Arnau de Vilanova de Lleida (HUAV). Se administró un cuestionario pre y post-intervención formativa, con un intervalo de cuatro meses. La formación consistió en una sesión formativa de una hora de duración dirigida a todos los profesionales del estudio sobre la importancia de aplicar las ocho recomendaciones más relevantes de la Care Bundle. Se llevó a cabo un análisis descriptico y bivariante. RESULTADOS: participaron 150 (31%) profesionales en la fase pre y 184 (38%) en la fase post-intervención. Las dificultades más prevalentes en ambas fases fueron: retirar los catéteres innecesarios (38 (25,3%) vs. 32 (17,4%)), el mantenimiento diario del catéter (47 (31,3%) vs. 48 (26,1%)), el manejo y/o acceso higiénico al sistema circulatorio (44 (29,3) vs. 25 (13,6)) y recambiar los catéteres venosos periféricos según protocolo (68 (45,6) vs. 73 (39,7)). Los factores asociados con dichas dificultades fueron principalmente ser enfermera (p< 0,05) y las unidades de trabajo quirúrgica (p< 0,05) y hospitalización (p< 0,05). CONCLUSIONES: las dificultades más prevalentes en el cumplimiento de las recomendaciones según la Care Bundle fueron retirar los catéteres innecesarios, el mantenimiento diario de las vías centrales y/o periféricas, el manejo y/o acceso higiénico al sistema circulatorio a través del CVC o periférico, y el recambio de los catéteres venosos periféricos según el protocolo. Los factores asociados a estas dificultades fueron la categoría profesional y la unidad donde se atiende al paciente

OBJECTIVE: to understand the difficulties for implementing the recommendations according to the Care Bundle in order to prevent the complications associated with vascular access devices, and to assess those factors associated with the difficulties identified. METHOD: a descriptive transversal study, with a population formed by clinicians and nurses from the Hospital Universitario Arnau de Vilanova (HUAV) in Lleida. A pre-and-post training intervention questionnaire was applied, with a 4-month-interval. Training consisted in a 1-hour training session targeted to all professionals in the study, on the importance of implementing the eight most relevant recommendations in the Care Bundle. Descriptive and bivariate analysis was conducted. RESULTS: the study included 150 (31%) professionals in the pre-intervention and 184 (38%) in the post-intervention stages. The most prevalent difficulties in both stages were: removing unnecessary catheters (38 (25.3%) vs. 32 (17.4%)), daily maintenance of catheters (47 (31.3%) vs. 48 (26.1%)), hygienic management and/or access to the circulatory system (44 (29.3) vs. 25 (13.6)) and replacing peripheral vein catheters according to protocol (68 (45.6) vs. 73 (39.7)). The factors associated with both difficulties were: mainly being a nurse (p< 0.05) and the surgical (p< 0.05) and hospitalization work units (p< 0.05). CONCLUSIONS: the most prevalent difficulties for implementing the recommendations according to the Care Bundle were: removing unnecessary catheters, daily maintenance of central and/or peripheral IV lines, hygienic management and/or access to the circulatory system through central or peripheral venous catheter, and replacing peripheral vein catheters according to protocol. The factors associated with these difficulties were professional category and the unit where the patient is managed

Analyzing the impact of duration of ventilation, hospitalization, and ventilation episodes on the risk of pneumonia.

OBJECTIVE: To study the impact of duration of mechanical ventilation, hospitalization and multiple ventilation episodes on the development of pneumonia while accounting for extubation as a competing event. DESIGN: A multicenter data base from a Spanish surveillance network was used to conduct a retrospective analysis of prospectively collected intensive care patients followed from admission to discharge. SETTING: Spanish intensive care units (ICUs). PATIENTS: Mechanically ventilated adult patients from 158 ICUs with 45,486 admissions, 48,705 ventilation episodes, and 314,196 ventilator days. METHODS: Competing-risk models were applied to account for extubation plus 48 hours as a competing event for acquiring ventilator-associated pneumonia (VAP). RESULTS: Time in the ICU before mechanical ventilation was associated with an increased VAP hazard rate and with longer intubation time. This indirect prolongation of intubation increased the cumulative risk to eventually acquire VAP. For instance, comparing 3-4 versus 0 days, the adjusted VAP hazard ratio was 1.40 (95% confidence interval [CI], 1.19-1.64) and the adjusted extubation hazard ratio was 0.64 (95% CI, 0.61-0.68), which leads to an adjusted VAP subdistribution hazard ratio (sHR) of 2.13 (95% CI, 1.83-2.50). Similarly, due to prolonged intubation, multiple ventilation episodes increase the risk for VAP; the adjusted sHR is 1.52 (95% CI, 1.35-1.72) for the second episode compared to the first episode, and the adjusted sHR is 1.54 (95% CI, 1.03-2.30) for the third episode compared to the first episode. The Kaplan-Meier method produced an upward biased estimated cumulative risk for VAP. CONCLUSIONS: A competing-risk analysis is necessary to receive unbiased risk estimates and to quantify the indirect effect of intubation time on the cumulative VAP risk. Our findings may guide physicians to improve medical decisions related to the harms and benefits of the duration of ventilation.

Barreras y facilitadores en la adherencia al care bundle para prevenir complicaciones asociadas a dispositivos de acceso vascular / Barriers and drivers for adherence to the care bundle in order to prevent complications associated with vascular access devices

Objetivo: identificar barreras y facilitadores en la adherencia al care bundle para prevenir complicaciones asociadas a dispositivos de acceso vascular; y describirlas en función de las características sociodemográficas y laborales de los profesionales sanitarios implicados. Método: estudio descriptivo transversal. Población: médicos y enfermeras del Hospital Universitario Arnau de Vilanova de Lleida. Instrumento: cuestionario formado por tres bloques: 13 ítems sobre organización del servicio, 16 ítems sobre liderazgo del servicio y ocho sobre recomendaciones del protocolo hospitalario. Análisis bivariante mediante Chi cuadrado y ANOVA. Resultados: participaron 150 profesionales, la mayoría enfermeras (80%). De manera estadísticamente significativa (p< 0,05), las personas de 60 años o más obtuvieron la puntuación más baja en "aplicación el care bundle", y los de 29 años o menos consideraron que estaban menos educados y entrenados en su aplicación; quienes tenían menor experiencia puntuaron por debajo en "conocimiento del protocolo", se consideraron menos entrenados en la aplicación del care bundle, se sentían menos preparados, tenían menos conocimiento de su propio cumplimiento, no aplicaban correctamente el care bundle, ni de forma regular y su opinión sobre la formación fue que no modificaba su práctica clínica. Conclusiones: el cuestionario identifica aspectos mejorables en el protocolo hospitalario sobre dispositivos de acceso vascular, causas de dificultad en la aplicación del bundle y falta de formación continuada hacia el personal, sobre todo el de nueva incorporación

Objective: to identify the barriers and drivers for adherence to the care bundle in order to prevent complications associated with vascular access devices, and to describe them based on the sociodemographical and occupational characteristics of the healthcare professionals involved. Method: a descriptive cross-sectional study. Population: physicians and nurses from the Hospital Universitario Arnau de Vilanova of Lleida. Instrument: A questionnaire formed by three blocks: 13 items on structure of the service, 16 items about leadership of the service, and 8 about recommendations from the hospital protocol. A bivariate analysis through Chi-Square and ANOVA. Results: the study involved 150 professionals, most of them nurses (80%). In a statistically significant way (p< 0.05), ≥60-year-old persons obtained the lowest score in "applying the care bundle", and ≤29-year-old persons considered that they were less educated and trained for its application; those with lower experience had a lower score in "protocol knowledge", they considered they were less trained in the application of the care bundle, they felt less prepared and had lower knowledge of their own compliance, did not apply the care bundle adequately or regularly, and their opinion on training was that it did not modify their clinical practice. Conclusions: the questionnaire identified aspects that can be improved in the hospital protocol regarding vascular access devices, factors that cause difficulty in the application of the bundle, and lack of continuous training for the staff, particularly those recently incorporated

Improving nested case-control studies to conduct a full competing-risks analysis for nosocomial infections.

OBJECTIVE: Competing risks are a necessary consideration when analyzing risk factors for nosocomial infections (NIs). In this article, we identify additional information that a competing risks analysis provides in a hospital setting. Furthermore, we improve on established methods for nested case-control designs to acquire this information. METHODS: Using data from 2 Spanish intensive care units and model simulations, we show how controls selected by time-dynamic sampling for NI can be weighted to perform risk-factor analysis for death or discharge without infection. This extension not only enables hazard rate analysis for the competing risk, it also enables prediction analysis for NI. RESULTS: The estimates acquired from the extension were in good agreement with the results from the full (real and simulated) cohort dataset. The reduced dataset results averted any false interpretation common in a competing-risks setting. CONCLUSIONS: Using additional information that is routinely collected in a hospital setting, a nested case-control design can be successfully adapted to avoid a competing risks bias. Furthermore, this adapted method can be used to reanalyze past nested case-control studies to enhance their findings.

Methodological challenges in using point-prevalence versus cohort data in risk factor analyses of nosocomial infections.

PURPOSE: To explore the impact of length-biased sampling on the evaluation of risk factors of nosocomial infections (NIs) in point-prevalence studies. METHODS: We used cohort data with full information including the exact date of the NI and mimicked an artificial 1-day prevalence study by picking a sample from this cohort study. Based on the cohort data, we studied the underlying multistate model which accounts for NI as an intermediate and discharge/death as competing events. Simple formulas are derived to display relationships between risk, hazard, and prevalence odds ratios. RESULTS: Due to length-biased sampling, long stay and thus sicker patients are more likely to be sampled. In addition, patients with NIs usually stay longer in hospital. We explored mechanisms that are-due to the design-hidden in prevalence data. In our example, we showed that prevalence odds ratios were usually less pronounced than risk odds ratios but more pronounced than hazard ratios. CONCLUSIONS: Thus, to avoid misinterpretation, knowledge of the mechanisms from the underlying multistate model is essential for the interpretation of risk factors derived from point-prevalence data.

Prevention of Ventilator-Associated Pneumonia: The Multimodal Approach of the Spanish ICU "Pneumonia Zero" Program.

OBJECTIVES: The "Pneumonia Zero" project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU. DESIGN: Prospective, interventional, and multicenter study. SETTING: A total of 181 ICUs throughout Spain. PATIENTS: All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012. INTERVENTION: Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April-June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status. MEASUREMENTS AND MAIN RESULTS: The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42-11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22-5.84) after 19-21 months of participation. CONCLUSIONS: Implementation of the bundle measures included in the "Pneumonia Zero" project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation.

Mucormicosis renal grave en un paciente crítico / Isolated renal mucormycosis in a critically ill patient

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A case-cohort approach for multi-state models in hospital epidemiology.

Analysing the determinants and consequences of hospital-acquired infections involves the evaluation of large cohorts. Infected patients in the cohort are often rare for specific pathogens, because most of the patients admitted to the hospital are discharged or die without such an infection. Death and discharge are competing events to acquiring an infection, because these individuals are no longer at risk of getting a hospital-acquired infection. Therefore, the data is best analysed with an extended survival model - the extended illness-death model. A common problem in cohort studies is the costly collection of covariate values. In order to provide efficient use of data from infected as well as uninfected patients, we propose a tailored case-cohort approach for the extended illness-death model. The basic idea of the case-cohort design is to only use a random sample of the full cohort, referred to as subcohort, and all cases, namely the infected patients. Thus, covariate values are only obtained for a small part of the full cohort. The method is based on existing and established methods and is used to perform regression analysis in adapted Cox proportional hazards models. We propose estimation of all cause-specific cumulative hazards and transition probabilities in an extended illness-death model based on case-cohort sampling. As an example, we apply the methodology to infection with a specific pathogen using a large cohort from Spanish hospital data. The obtained results of the case-cohort design are compared with the results in the full cohort to investigate the performance of the proposed method. Copyright © 2016 John Wiley & Sons, Ltd.

Miocarditis aguda candidiásica en un paciente crítico / Acute Candida myocarditis in a critical care patient

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Risk factors for methicillin-resistant Staphylococcus aureus colonisation or infection in intensive care units and their reliability for predicting MRSA on ICU admission.

Predicting methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) avoids inappropriate antimicrobial empirical treatment and enhances infection control. We describe risk factors for colonisation/infection related to MRSA (MRSA-C/I) in critically ill patients once in the ICU and on ICU admission, and search for an easy-to-use predictive model for MRSA colonisation/infection on ICU admission. This multicentre cohort study included 69,894 patients admitted consecutively (stay>24h) in April-June in the five-year period 2006-2010 from 147 Spanish ICUs participating in the National Surveillance Study of Nosocomial Infections in ICUs (ENVIN-HELICS). Data from all patients included were used to identify risk factors for MRSA-C/I during ICU stays, from admission to discharge, using uni- and multivariable analysis (Poisson regression) to check that the sample to be used to develop the predictive models was representative of standard critical care population. To identify risk factors for MRSA-C/I on ICU admission and to develop prediction models, multivariable logistic regression analysis were then performed only on those admitted in 2010 (n=16950, 2/3 for analysis and 1/3 for subsequent validation). We found that, in the period 2006-2010, 1046 patients were MRSA-C/I. Independent risk factors for MRSA-C/I in ICU were: age>65, trauma or medical patient, high APACHE-II score, admitted from a long-term care facility, urinary catheter, previous antibiotic treatment and skin-soft tissue or post-surgical superficial skin infections. Colonisation with several different MDRs significantly increased the risk of MRSA-C/I. Risk factors on ICU admission were: male gender, trauma critical patient, urgent surgery, admitted from other ICUs, hospital ward or long-term facility, immunosuppression and skin-soft tissue infection. Although the best model to identify carriers of MRSA had a good discrimination (AUC-ROC, 0.77; 95% CI, 0.72-0.82), sensitivity was 67% and specificity 76.5%. Including more complex variables did not improve prediction capability. Our conclusion is that clinical-demographic risk factors for colonisation/infection related to MRSA should not be used to accurately identify patients who would benefit from empirical anti-MRSA treatment or from specific preventive measures. Independent risk factors for MRSA colonisation/infection during ICU stay and on ICU admission are described. The latter should be considered in future studies for MRSA prediction.

Multiple time scales in modeling the incidence of infections acquired in intensive care units.

BACKGROUND: When patients are admitted to an intensive care unit (ICU) their risk of getting an infection will be highly depend on the length of stay at-risk in the ICU. In addition, risk of infection is likely to vary over calendar time as a result of fluctuations in the prevalence of the pathogen on the ward. Hence risk of infection is expected to depend on two time scales (time in ICU and calendar time) as well as competing events (discharge or death) and their spatial location. The purpose of this paper is to develop and apply appropriate statistical models for the risk of ICU-acquired infection accounting for multiple time scales, competing risks and the spatial clustering of the data. METHODS: A multi-center data base from a Spanish surveillance network was used to study the occurrence of an infection due to Methicillin-resistant Staphylococcus aureus (MRSA). The analysis included 84,843 patient admissions between January 2006 and December 2011 from 81 ICUs. Stratified Cox models were used to study multiple time scales while accounting for spatial clustering of the data (patients within ICUs) and for death or discharge as competing events for MRSA infection. RESULTS: Both time scales, time in ICU and calendar time, are highly associated with the MRSA hazard rate and cumulative risk. When using only one basic time scale, the interpretation and magnitude of several patient-individual risk factors differed. Risk factors concerning the severity of illness were more pronounced when using only calendar time. These differences disappeared when using both time scales simultaneously. CONCLUSIONS: The time-dependent dynamics of infections is complex and should be studied with models allowing for multiple time scales. For patient individual risk-factors we recommend stratified Cox regression models for competing events with ICU time as the basic time scale and calendar time as a covariate. The inclusion of calendar time and stratification by ICU allow to indirectly account for ICU-level effects such as local outbreaks or prevention interventions.

Trends in nosocomial infections and multidrug-resistant microorganisms in Spanish pediatric intensive care units / Tendencia de la infección nosocomial y microorganismos multirresistentes en unidades de cuidados intensivos pediátricas en España

INTRODUCTION: Nosocomial infections (NI) are a major healthcare problem. National surveillance systems enable data to be compared and to implement new measures to improve our practice. METHODS: A multicentre, prospective, descriptive and observational study was conducted using the data from surveillance system for nosocomial infections created in 2007 for Spanish pediatric intensive care units. Data were collected for one month, between 01 and 31 March, for every study year (2008-2012). The objective was to report 5-years of NI surveillance data, as well as trends in infections by multidrug resistant organisms in Spanish pediatric intensive care units. RESULTS: A total of 3667 patients were admitted to the units during the study period. There were 90 (2.45%) patients with nosocomial infections. The mean rates during the 5 years study were: central line-associated bloodstream infection, 3.8/1000 central venous catheter-days, Ventilator-associated pneumonia 7.5/1000 endotracheal tube-days, and catheter-associated urinary tract infections 4.1/1000 urinary catheter-days. The comparison between the 2008 and 2009 rates for nosocomial infections did not show statistically significant differences. All rates homogeneously decreased from 2009 to 2012: central line-associated bloodstream infection 5.83 (95% CI 2.67-11.07) to 0.49 (95% CI 0.0125-2.76), P = 0.0029; ventilator-associated pneumonia 10.44 (95% CI 5.21-18.67) to 4.04 (95% CI 1.48-8.80), P = 0.0525; and Catheter-associated urinary tract infections 7.10 (95% CI 3.067-13.999) to 2.56 (95% CI 0.697-6.553), P = 0.0817; respectively. The microorganism analysis: 63 of the 99 isolated bacteria (63.6%) were Gram-negative bacteria (36.5% were resistant), 19 (19.2%) Gram-positive bacteria, and 17 (17.2%) were Candida spp. infections. CONCLUSIONS: The local surveillance systems provide information for dealing with nosocomial infections rates

INTRODUCCIÓN: Las infecciones nosocomiales son un problema de salud pública. Los sistemas nacionales de vigilancia permiten comparar datos e implementar medidas para mejorar la práctica asistencial. MÉTODO: Estudio multicéntrico, prospectivo, descriptivo y observacional. En 2007 se creó un sistema de vigilancia para infección nosocomial en las Unidades de Cuidados Intensivos Pediátricas Españolas. Se recogieron datos durante un mes (Marzo) por año (2008-2012). El objetivo fue reportar las tasas de los 5 años de vigilancia de la infección nosocomial y la evolución de las infecciones por microorganismos multirresistentes. RESULTADOS: Ingresaron 3667 pacientes. Número de pacientes con infección nosocomial: 90 (2.45%). Tasas medias de los 5 años de estudio: Bacteriemia relacionada con catéter 3.8/1000 días de catéter venoso central, Neumonía asociada a la ventilación mecánica 7.5/1000 días de tubo endotraqueal e Infecciones urinarias asociadas a sonda 4.1/1000 días de sonda urinaria. La comparación de tasas entre 2008 y 2009 no mostró diferencias estadísticamente significativas. Todas las tasas se redujeron homogéneamente desde 2009 a 2012: Bacteriemia relacionada con catéter 5.83 (95% CI 2.67-11.07) a 0.49 (95% CI 0.0125-2.76), P = 0.0029; Neumonía asociada a la ventilación mecánica 10.44 (95% CI 5.21-18.67) a 4.04 (95% CI 1.48-8.80), P = 0.0525; Infecciones urinarias asociadas a sonda 7.10 (95% CI 3.067-13.999) a 2.56 (95% CI 0.697-6.553), P = 0.0817; respectivamente. Microorganismos: 63 de 99 (83.6%) microorganismos aislados fueron bacterias gram-negativas (36.5% resistentes), 19 (19.2%) bacterias gram-positivas y 17 (17.2%) infecciones por Candida spp. CONCLUSIONES: Los sistemas de vigilancia local aportan información para mejorar las tasas de infección nosocomial

Trends in nosocomial infections and multidrug-resistant microorganisms in Spanish pediatric intensive care units.

INTRODUCTION: Nosocomial infections (NI) are a major healthcare problem. National surveillance systems enable data to be compared and to implement new measures to improve our practice. METHODS: A multicentre, prospective, descriptive and observational study was conducted using the data from surveillance system for nosocomial infections created in 2007 for Spanish pediatric intensive care units. Data were collected for one month, between 01 and 31 March, for every study year (2008-2012). The objective was to report 5-years of NI surveillance data, as well as trends in infections by multidrug resistant organisms in Spanish pediatric intensive care units. RESULTS: A total of 3667 patients were admitted to the units during the study period. There were 90 (2.45%) patients with nosocomial infections. The mean rates during the 5 years study were: central line-associated bloodstream infection, 3.8/1000 central venous catheter-days, Ventilator-associated pneumonia 7.5/1000 endotracheal tube-days, and catheter-associated urinary tract infections 4.1/1000 urinary catheter-days. The comparison between the 2008 and 2009 rates for nosocomial infections did not show statistically significant differences. All rates homogeneously decreased from 2009 to 2012: central line-associated bloodstream infection 5.83 (95% CI 2.67-11.07) to 0.49 (95% CI 0.0125-2.76), P=0.0029; ventilator-associated pneumonia 10.44 (95% CI 5.21-18.67) to 4.04 (95% CI 1.48-8.80), P=0.0525; and Catheter-associated urinary tract infections 7.10 (95% CI 3.067-13.999) to 2.56 (95% CI 0.697-6.553), P=0.0817; respectively. The microorganism analysis: 63 of the 99 isolated bacteria (63.6%) were Gram-negative bacteria (36.5% were resistant), 19 (19.2%) Gram-positive bacteria, and 17 (17.2%) were Candida spp. infections. CONCLUSIONS: The local surveillance systems provide information for dealing with nosocomial infections rates.

A full competing risk analysis of hospital-acquired infections can easily be performed by a case-cohort approach.

OBJECTIVES: We provide a case-cohort approach and show that a full competing risk analysis is feasible even in a reduced data set. Competing events for hospital-acquired infections are death or discharge from the hospital because they preclude the observation of such infections. STUDY DESIGN AND SETTING: Using surveillance data of 6,568 patient admissions (full cohort) from two Spanish intensive care units, we propose a case-cohort approach which uses only data from a random sample of the full cohort and all infected patients (the cases). We combine established methodology to study following measures: event-specific as well as subdistribution hazard ratios for all three events (infection, death, and discharge), cumulative hazards as well as incidence functions by risk factor, and also for all three events. RESULTS: Compared with the values from the full cohort, all measures are well approximated with the case-cohort design. For the event of interest (infection), event-specific and subdistribution hazards can be estimated with the full efficiency of the case-cohort design. So, standard errors are only slightly increased, whereas the precision of estimated hazards of the competing events is inflated according to the size of the subcohort. CONCLUSION: The case-cohort design provides an appropriate sampling design for studying hospital-acquired infections in a reduced data set. Potential effects of risk factors on the competing events (death and discharge) can be evaluated.