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.

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.

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.

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.

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.

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.

Multilevel competing risk models to evaluate the risk of nosocomial infection.

INTRODUCTION: Risk factor analyses for nosocomial infections (NIs) are complex. First, due to competing events for NI, the association between risk factors of NI as measured using hazard rates may not coincide with the association using cumulative probability (risk). Second, patients from the same intensive care unit (ICU) who share the same environmental exposure are likely to be more similar with regard to risk factors predisposing to a NI than patients from different ICUs. We aimed to develop an analytical approach to account for both features and to use it to evaluate associations between patient- and ICU-level characteristics with both rates of NI and competing risks and with the cumulative probability of infection. METHODS: We considered a multicenter database of 159 intensive care units containing 109,216 admissions (813,739 admission-days) from the Spanish HELICS-ENVIN ICU network. We analyzed the data using two models: an etiologic model (rate based) and a predictive model (risk based). In both models, random effects (shared frailties) were introduced to assess heterogeneity. Death and discharge without NI are treated as competing events for NI. RESULTS: There was a large heterogeneity across ICUs in NI hazard rates, which remained after accounting for multilevel risk factors, meaning that there are remaining unobserved ICU-specific factors that influence NI occurrence. Heterogeneity across ICUs in terms of cumulative probability of NI was even more pronounced. Several risk factors had markedly different associations in the rate-based and risk-based models. For some, the associations differed in magnitude. For example, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with modest increases in the rate of nosocomial bacteremia, but large increases in the risk. Others differed in sign, for example respiratory vs cardiovascular diagnostic categories were associated with a reduced rate of nosocomial bacteremia, but an increased risk. CONCLUSIONS: A combination of competing risks and multilevel models is required to understand direct and indirect risk factors for NI and distinguish patient-level from ICU-level factors.

Nested case-control studies in cohorts with competing events.

In nested case-control studies, incidence density sampling is the time-dependent matching procedure to approximate hazard ratios. The cumulative incidence function can also be estimated if information from the full cohort is used. In the presence of competing events, however, the cumulative incidence function depends on the hazard of the disease of interest and on the competing events hazard. Using hospital-acquired infection as an example (full cohort), we propose a sampling method for nested case-control studies to estimate subdistribution hazard ratios. With further information on the full cohort, the cumulative incidence function for the event of interest can then be estimated as well.

[Analysis of treatments used in infections caused by gram-positive multiresistant cocci in critically ill patients admitted to the ICU]. / Análisis de los tratamientos utilizados en las infecciones por cocos grampositivos multirresistentes en pacientes críticos ingresados en UCI.

UNLABELLED: The appearance of new antimicrobials with activity against Gram-positive multiresistant cocci and knowledge of the limitations of glycopeptides has represented an important change in the use of these antibiotics. OBJECTIVE: To analyze at the national level changes in the use of antibiotics with specific activity against Gram-positive multiresistant cocci in critically ill patients admitted to the ICU as well as the characteristics of patients treated with these agents and the forms of administration. MATERIAL AND METHODS: Retrospective cohort study of patients admitted to the ICU for more than 24 hours between 2008 and 2010 in the ENVIN-HELICS national registry. Cases were defined as patients who had received one or more of the following antibiotics: vancomycin, teicoplanin, linezolid or daptomycin. The characteristics of patients who used one or more of these agents were compared with those treated with other antibiotics. Indications and forms of use of each antibiotic were assessed. Descriptive results are presented. RESULTS: A total of 45,757 patients, 27,982 (61.2%) of whom received 63,823 antimicrobials were included in the study. In 6,368 (13.9%) patients, one or more antibiotics specifically active against Gram-positive multiresistant cocci were given. There was a predominance of the use of vancomycin and linezolid and an important increase in the prescription of daptomycin (+320%) and linezolid (+22.4%). In more than 95% of cases, linezolid and daptomycin were prescribed for the treatment of infections, whereas vancomycin and teicoplanin were used for prophylaxis in 20-25% of cases. Between 75% and 80% of indications for treating infections, antibiotics were used empirically except for daptomycin which was used as a directed treatment in 43% of the cases. Only in one third of the indications for empirical treatment, susceptible microorganisms were identified (appropriate treatment). CONCLUSIONS: The use of antibiotics with activity against Gram-positive multiresistant cocci remained stable around 14% of all indications. The use of vancomycin and linezolid predominated and there was a clear trend towards an increase in the use of daptomycin and linezolid and a decrease in the use of glycopeptides. Empirical treatments were considered appropriate in only one third of cases.

[Trends in systemic antifungal use in critically ill patients. Multicenter observational study, 2006-2010]. / Evolución del consumo de antifúngicos en pacientes críticos. Estudio multicéntrico observacional, 2006-2010.

INTRODUCTION: There are limited data about the use of antifungal agents (AF) in critically ill patients and treatment trends since the inclusion of the new generation AF. The use of these agents may have a significant influence on the development of new resistances. METHODS: Observational prospective study of the systemic use of AF in patients admitted to Spanish intensive care units (ICU) participating in the ENVIN-HELICS register, from 2006 to 2010. The annual use, the indications that led to that use and, the intra-ICU infections, the AF employment related to the hospital size, and per 1000 patients/day, were compared. RESULTS: Of the 8240 prescriptions for AF, fluconazole and caspofungin were the most often employed (55% and 19.5%, respectively). An increase in use was observed to the year 2008, with subsequent stabilisation. A decrease in the use of fluconazole and an increase in echinocandins consumption was observed over time. As regards the intra-ICU infections, the AF were ordered empirically in 47.9% of the indications. Fluconazole was more frequently used in medium size hospitals than in the large ones (60.4% versus 53.3%; P=.036) and the opposite occurred in the case of caspofungin (15.8% versus 21.8%; P<.001). Fluconazole was more prematurely employed (median 12 days since ICU admission) and the duration of the therapy was similar to the other AF (median 8 days). The total therapy days were 39.51 per 1000 patient/day, with predominance in fluconazole use (21.48 per 1000 patients/day). CONCLUSIONS: Fluconazole is the most used antifungal agent in critically ill patients in any of the indications, although a progressive decrease in its use is observed, with a proportional increase in the use of echinocandins.

Risk factors and prognosis of catheter-related bloodstream infection in critically ill patients: a multicenter study.

OBJECTIVE: To assess the risk factors associated with CR-BSI development in critically ill patients with non-tunneled, non-cuffed central venous catheters (CVC) and the prognosis of the episodes of CR-BSI. Design and setting; prospective, observational, multicenter study in nine Spanish Hospitals. PATIENTS: All subjects admitted to the participating ICUs from October 2004 to June 2005 with a CVC. INTERVENTIONS: None. MEASUREMENT AND RESULTS: Overall, 1,366 patients were enrolled and 2,101 catheters were analyzed. Sixty-six episodes of CR-BSI were diagnosed. The incidence of CR-BSI was significantly higher in CVC compared with peripherically inserted central venous catheters (PICVC) without significant differences among the three locations of CVC. In the multivariate analysis, duration of catheterization and change over a guidewire were the independent variables associated with the development of CR-BSI whereas the use of a PICVC was a protective factor. Excluding PICVC, 1,598 conventional CVC were analyzed. In this subset, duration of catheterization, tracheostomy and change over a guidewire were independent risk factors for CR-BSI. A multivariate analysis of predictors for mortality among 66 patients with CRSI showed that early removal of the catheter was a protective factor and APACHE II score at the admission was a strong determinant of in-hospital mortality. CONCLUSIONS: Peripherically inserted central venous catheters is associated with a lower incidence of CR-BSI in critically ill patients. Exchange over a guidewire of CVC and duration of catheterization are strong contributors to CR-BSI. Our results reinforce the importance of early catheter removal in critically ill patients with CR-BSI.