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Background: Delirium is frequent in patients in the ICU, but its association with the outcome of weaning from mechanical ventilation has not been assessed. Circadian rhythm alteration may favor delirium. In the current study, we assessed the impact of delirium during weaning and associated alterations in the circadian rhythm of melatonin excretion., Methods: This was a substudy of 70 participants of the B-type Natriuretic Peptide for the Fluid Management of Weaning trial, comparing two fluid management strategies during weaning. Patients with or without delirium (as assessed using the Confusion Assessment Method for the ICU) were compared in terms of baseline characteristics and outcomes and the circadian rhythm of melatonin excretion using the 24-h excretion of its urinary metabolite 6-sulfatoxymelatonin (aMT6s)., Results: Among the 70 patients included, 43 (61.4%) experienced delirium at the initiation of weaning. Delirium at the initiation of weaning was associated with more alcohol consumption, a greater severity of illness, and medication use before weaning (including neuromuscular blockade, antibiotics, sedatives, and narcotics). Delirium at the initiation of weaning was associated with more respiratory and neurologic complications and a reduced probability of successful extubation (Cox multivariate model hazard ratio of successful extubation = 0.54; 95% CI, 0.30-0.95; P = .03). Delirium was also associated with a significant reduction in peak, mean, amplitude, and total values of aMT6s urinary excretion during the first 24 h of weaning (general linear model F statistic = 5.81, P = .019)., Conclusions: Delirium is frequent at the initiation of ventilator weaning. It is associated with a prolongation of weaning and an alteration in the circadian rhythm of melatonin excretion., Trial Registry: ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov.

Objectives: Infections caused by carbapenemase-producing Enterobacteriaceae are increasing worldwide, especially in ICUs, and have been associated with high mortality rates. However, unequivocally demonstrating causality of such infections to death is difficult in critically ill patients because of potential confounding and competing events. Here, we quantified the effects of carbapenemase-producing Enterobacteriaceae carriage on patient outcome in two Greek ICUs with carbapenemase-producing Enterobacteriaceae endemicity., Design: Observational cohort study., Setting: Two ICUs with carbapenemase-producing Enterobacteriaceae endemicity., Patients: Patients admitted to the ICU with an expected length of ICU stay of at least 3 days were included., Interventions: None., Measurements and Main Results: Carbapenemase-producing Enterobacteriaceae colonization was established through screening in perineum swabs obtained at admission and twice weekly and inoculated on chromogenic plates. Detection of carbapenemases was performed phenotypically, with confirmation by polymerase chain reaction. Risk factors for ICU mortality were evaluated using cause-specific hazard ratios and subdistribution hazard ratios, with carbapenemase-producing Enterobacteriaceae colonization as time-varying covariate. One thousand seven patients were included, 36 (3.6%) were colonized at admission, and 96 (9.5%) acquired carbapenemase-producing Enterobacteriaceae colonization during ICU stay, and 301 (29.9%) died in ICU. Of 132 carbapenemase-producing Enterobacteriaceae isolates, 125 (94.7%) were Klebsiella pneumoniae and 74 harbored K. pneumoniae carbapenemase (56.1%), 54 metallo-β-lactamase (40.9%), and four both (3.0%). Carbapenemase-producing Enterobacteriaceae colonization was associated with a statistically significant increase of the subdistribution hazard ratio for ICU mortality (subdistribution hazard ratio=1.79; 95% CI, 1.31-2.43), not explained by an increased daily hazard of dying (cause-specific hazard ratio for death=1.02; 95% CI, 0.74-1.41), but by an increased length of stay (cause-specific hazard ratio for discharge alive=0.73; 95% CI, 0.51-0.94). Other risk factors in the subdistribution hazard model were Acute Physiology and Chronic Health Evaluation II score (subdistribution hazard ratio=1.13; 95% CI, 1.11-1.15), female gender (subdistribution hazard ratio=1.29; 95% CI, 1.02-1.62), presence of solid tumor (subdistribution hazard ratio=1.54; 95% CI, 1.15-2.06), hematopoietic malignancy (subdistribution hazard ratio=1.61; 95% CI, 1.04-2.51), and immunodeficiency (subdistribution hazard ratio=1.59; 95% CI, 1.11-2.27)., Conclusions: Patients colonized with carbapenemase-producing Enterobacteriaceae have on average a 1.79 times higher hazard of dying in ICU than noncolonized patients, primarily because of an increased length of stay.

Objective: The influence of delirium, ICU-acquired paresis, and cardiac performance on extubation outcome has never been evaluated together. We aimed to assess the respective role of these factors on the risk of extubation failure and to assess the predictive accuracy of caregivers., Design and Setting: Prospective observational study of all planned extubations in a 13-bed medical ICU of a teaching hospital., Interventions: On the day of extubation, muscle strength of the four limbs, criteria for delirium, cardiac performance, cough strength, and the risk of extubation failure predicted by caregivers were prospectively assessed. Extubation failure was defined as the need for reintubation within the following 7 days., Measurements and Main Results: Over the 18-month study period, 533 patients required intubation. Among the 225 patients intubated for more than 24 hours who experienced a planned extubation attempt, 31 patients (14%) required reintubation within the 7 days following extubation. In multivariate analysis, duration of mechanical ventilation more than 7 days prior to extubation, ineffective cough, and severe systolic left ventricular dysfunction were the three independent factors associated with extubation failure. Although patients considered at high risk for extubation failure had higher reintubation rate, prediction of extubation failure by caregivers at time of extubation had high specificity but low sensitivity., Conclusions: An ineffective cough, a prior duration of mechanical ventilation more than 7 days, and severe systolic left ventricular dysfunction were stronger predictors of extubation failure than delirium or ICU-acquired weakness. Only one-third patients who required reintubation were considered at high risk for extubation failure by caregivers.

During the 2009/10 pandemic, a national surveillance system for severe influenza cases was set up in France. We present results from the system's first four years. All severe influenza cases admitted to intensive care units (ICU) were reported to the Institut de Veille Sanitaire using a standardised form: data on demographics, immunisation and virological status, risk factors, severity (e.g. acute respiratory distress syndrome (ARDS) onset, mechanical ventilation, extracorporeal life support) and outcome. Multivariate analysis was performed to identify factors associated with ARDS and death. The number of confirmed influenza cases varied from 1,210 in 2009/10 to 321 in 2011/12. Most ICU patients were infected with A(H1N1)pdm09, except during the 2011/12 winter season when A(H3N2)-related infections predominated. Patients' characteristics varied according to the predominant strain. Based on multivariate analysis, risk factors associated with death were age ≥ 65 years, patients with any of the usual recommended indications for vaccination and clinical severity. ARDS occurred more frequently in patients who were middle-aged (36-55 years), pregnant, obese, or infected with A(H1N1)pdm09. Female sex and influenza vaccination were protective. These data confirm the persistent virulence of A(H1N1)pdm09 after the pandemic and the heterogeneity of influenza seasons, and reinforce the need for surveillance of severe influenza cases.

The current paradigm for antibiotic management in critically ill patients is to initiate broad-spectrum therapy followed by de-escalation based on microbiological results. Routine screening cultures may allow better targeting and reduce unnecessary exposure to antibiotics.

Purpose: Readmission of patients colonized with antimicrobial-resistant bacteria (AMRB) is important in the nosocomial dynamics of AMRB. We assessed the duration of colonization after discharge from the intensive care unit (ICU) with highly resistant Enterobacteriaceae (HRE), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE)., Methods: Data were obtained from a cluster-randomized trial in 13 ICUs in 8 European countries (MOSAR-ICU trial, 2008-2011). All patients were screened on admission and twice weekly for AMRB. All patients colonized with HRE, MRSA, or VRE and readmitted to the same ICU during the study period were included in the current analysis. Time between discharge and readmission was calculated, and the colonization status at readmission was assessed. Because of interval-censored data, a maximum likelihood analysis was used to calculate the survival function, taking censoring into account. A nonparametric two-sample test was used to test for differences in the survival curves., Results: The MOSAR-ICU trial included 14,390 patients, and a total of 64,997 cultures were taken from 8,974 patients admitted for at least 3 days. One hundred twenty-five unique patients had 141 episodes with AMRB colonization and at least 1 readmission. Thirty-two patients were colonized with two or more AMRBs. Median times until clearance were 4.8 months for all AMRB together, 1.4 months for HRE, <1 month for MRSA, and 1.5 months for VRE. There were no significant differences between the survival curves., Conclusion: Fifty percent of the patients had lost colonization when readmitted 2 or more months after previous ICU discharge.

Background: Intensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs., Methods: We did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12-15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638., Findings: Seven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954-0·999) for phase 2 and 1·015 (0·998-1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676-1·348) for phase 2 and 0·634 (0·349-1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890-0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06)., Interpretation: Improved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing., Funding: European Commission., (Copyright © 2014 Derde et al. Open Access article distributed under the terms of CC BY-NC-SA. Published by Elsevier Ltd. All rights reserved.)

Introduction: The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs., Methods: We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden., Results: Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas., Conclusions: The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.

Objectives: The objective was to compare outcomes associated with early, late, and no admission to the intensive care unit (ICU) for patients hospitalized with community-acquired pneumonia (CAP)., Methods: This was a post hoc analysis of the original data from the Emergency Department Community-Acquired Pneumonia (EDCAP) and Pneumocom-1 prospective multicenter cohort studies of adult patients hospitalized with CAP. Propensity score-adjusted analysis was used to compare 28-day mortality and hospital length of stay (LOS) for 199, 144, and 2,215 patients with early (i.e., ICU admission on the day of emergency department [ED] presentation), late, and no ICU admission., Results: Unadjusted 28-day mortality rates were 13.1, 19.4, and 5.7% for early, late, and no ICU admissions, respectively (p < 0.001). After adjusting for quintile of propensity score, the odds of 28-day mortality were higher for late ICU admissions relative to early ICU admissions (odds ratio [OR] = 2.63; 95% confidence interval [CI] = 1.42 to 4.90), and no ICU admissions (OR = 3.40; 95% CI = 2.11 to 5.48), but did not differ between early and no ICU admissions (OR = 1.29; 95% CI = 0.79 to 2.09). The median hospital LOS was 10 days for early (interquartile range [IQR] = 7 to 18), 15 days for late (IQR 9 to 23), and 6 days (IQR 4 to 9) for no ICU admissions (p < 0.001)., Conclusions: This study suggests that late but not early admission to the ICU is associated with higher 28-day mortality for patients hospitalized with CAP. Patients admitted to the ICU have longer hospital LOS in comparison to those managed on the wards, particularly if they are admitted late to the ICU., (© 2012 by the Society for Academic Emergency Medicine.)

Objective: Extubation failure is associated with a poor prognosis, but the respective roles for reintubation per se and underlying disease severity remain unclear. Our objectives were to evaluate the impact of failed extubation, whether planned or unplanned, on patient outcomes and to identify a patient subset at risk for extubation failure., Design: Prospective 1-yr observational study with daily data collection., Setting: : Thirteen-bed medical intensive care unit in a teaching hospital., Patients: Consecutive patients requiring invasive mechanical ventilation were screened and followed until discharge or death., Interventions: None., Measurements and Main Results: Of 168 planned extubations in 340 patients, 26 (15%) failed. Of these 26 patients, seven (27%) had pneumonia and 13 (50%) died after reintubation. Compared with successfully extubated patients, the patients with failed extubation were not significantly different regarding disease severity, mechanical ventilation duration, or blood gas values. Age and underlying diseases were the only factors associated with extubation failure, and extubation failure occurred in 34% of patients >65 yrs with chronic cardiac or respiratory disease compared with only 9% of other patients (p < .01). Unplanned extubation occurred in 9% of patients, and inadequate endotracheal tube position was a risk factor. Failure of both planned and unplanned extubation was specifically associated with significant rapid worsening of daily organ dysfunction scores., Conclusions: Patients >65 yrs with underlying chronic cardiac or respiratory disease are at high risk for extubation failure and subsequent pneumonia and death. Contrasting with successful extubation, failed planned or unplanned extubation was followed by marked clinical deterioration, suggesting a direct and specific effect of extubation failure and reintubation on patient outcomes.

Objective: To compare the 28-day mortality and hospital length of stay of patients with community-acquired pneumonia who were transferred to an intensive care unit on the same day of emergency department presentation (direct-transfer patients) with those subsequently transferred within 3 days of presentation (delayed-transfer patients)., Design: Secondary analysis of the original data from two North American and two European prospective, multicenter, cohort studies of adult patients with community-acquired pneumonia., Patients: In all, 453 non-institutionalized patients transferred within 3 days of emergency department presentation to an intensive care unit were included in the analysis. Supplementary analysis was restricted to patients without an obvious indication for immediate transfer to an intensive care unit., Interventions: None., Measurements and Main Results: The sample consisted of 138 delayed-transfer and 315 direct-transfer patients, among whom 150 (33.1%) were considered to have an obvious indication for immediate intensive care unit admission. After adjusting for the quintile of propensity score, delayed intensive care unit transfer was associated with an increased odds ratio for 28-day mortality (2.07; 95% confidence interval, 1.12-3.85) and a decreased odds ratio for discharge from hospital for survivors (0.53; 95% confidence interval, 0.39-0.71). In a propensity-matched analysis, delayed-transfer patients had a higher 28-day mortality rate (23.4% vs. 11.7%; p = 0.02) and a longer median hospital length of stay (13 days vs. 7 days; p < .001) than direct-transfer patients. Similar results were found after excluding the 150 patients with an obvious indication for immediate intensive care unit admission., Conclusions: Our findings suggest that some patients without major criteria for severe community-acquired pneumonia, according to the recent Infectious Diseases Society of America/American Thoracic Society consensus guideline, may benefit from direct transfer to the intensive care unit. Further studies are needed to prospectively identify patients who may benefit from direct intensive care unit admission despite a lack of major severity criteria for community-acquired pneumonia based on the current guidelines.

Introduction: To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3., Methods: Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support)., Results: A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population., Conclusions: The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions.

Objective: To assess adherence to clinical practice guidelines for three interventions routinely used in critical care medicine., Design and Setting: Multicenter, 1-day cross-sectional observational study in 44 intensive care units in four countries., Patients: A total of 419 patients hospitalized in participating ICUs on the day of the survey., Measurements and Results: Red blood cell transfusion (n = 29) was performed appropriately in 22 patients (76%), while among the 390 patients who received no transfusion 4 (1%) had a valid indication. Setting of tidal volume in acute respiratory distress syndrome, assessed in 45 patients, was deemed appropriate in 37 cases (82%). Prescription of stress ulcer prophylaxis (n = 128) was appropriate in only 24 patients (19%), while among the 268 patients who were not treated 28 (10%) had an indication., Conclusions: The implementation of recommendations varies across different domains of care. While the adherence to current recommendations in routine practice is acceptable as regards tidal volume settings in acute respiratory distress syndrome, it is suboptimal for blood transfusion and prevention of upper gastrointestinal bleeding. Practice surveys are useful to inform strategies currently developed to assess practices of health-care professionals and develop strategies for more effective dissemination of medical knowledge.

Objective: To characterize empiric antibiotic use in patients with suspected nosocomial ICU-acquired infections (NI), and determine the impact of prolonged therapy in the absence of infection., Design and Setting: Multicenter prospective cohort, with eight medical-surgical ICUs in North America and Europe., Patients: 195 patients with suspected NI., Methods: The diagnosis of NI was adjudicated by a blinded Clinical Evaluation Committee using retrospective review of clinical, radiological, and culture data., Results: Empiric antibiotics were prescribed for 143 of 195 (73.3%) patients with suspected NI; only 39 of 195 (20.0%) were adjudicated as being infected. Infection rates were similar in patients who did (26 of 143, 18.2%), or did not (13 of 52, 25.0%) receive empiric therapy (p = 0.3). Empiric antibiotics were continued for more than 4 days in 56 of 95 (59.0%) patients without adjudicated NI. Factors associated with continued empiric therapy were increased age (p = 0.02), ongoing SIRS (p = 0.03), and hospital (p = 0.004). Patients without NI who received empiric antibiotics for longer than 4 days had increased 28-day mortality (18 of 56, 32.1%), compared with those whose antibiotics were discontinued (3 of 39, 7.7%; OR = 5.7, 95% CI 1.5-20.9, p = 0.005). When the influence of age, admission diagnosis, vasopressor use, and multiple organ dysfunction was controlled by multivariable analysis, prolonged empiric therapy was not independently associated with mortality (OR = 3.8, 95% CI 0.9-15.5, p = 0.07)., Conclusions: Empiric antibiotics were initiated four times more often than NI was confirmed, and frequently continued in the absence of infection. We found no evidence that prolonged use of empiric antibiotics improved outcome for ICU patients, but rather a suggestion that the practice may be harmful.

Introduction: Decisions to withhold or withdraw active life support treatment in situations with no hope of improvement remain difficult for critical-care specialists and families; they are not always well understood by the public. This report describes terminal extubation, a particular method of withdrawing ventilator support., Methods: This retrospective analysis examines the records of patients who died in our intensive care unit after a decision to withdraw active life support by stopping artificial ventilation. Extubation was proposed for patients with irreversible neurological damage and was always performed only after a standardized collective decision-making process. This process included three stages. In the initial phase, withdrawal of ventilator support was discussed at a department staff meeting. The meeting's conclusions were transcribed into the medical file, and the possibility of extubation was raised with the family during a planned interview. At least a 24-hour period of reflection was necessary before a new interview, and any opposition, hesitation or lack of understanding by the family at this first interview resulted in suspending the decision. The technical procedures for terminal extubation were also standardized., Results: In 5 cases (4 men and one woman, with a mean age of 65 +/- 4 years), terminal extubation was decided in cooperation with the family, following an average of 3 interviews, 16 days after admission. All patients died within 3 days., Discussion: So-called "terminal" extubation, very common in the United States, but much less so in France, reinforces the transparency of end-of-life decisions in intensive care units and immediately makes tangible the end of the aggressive treatment for which critical-care specialists have been reproached. Since this first series of patients, extubation has been practiced in our department, principally in situations of irreversible neurological damage.

This report describes a retrospective analysis of 33 patients admitted to an intensive care unit with suspicion of necrotising fasciitis (NF) of the extremities. The aim of the study was to clarify the clinical presentation of NF in order to determine when early surgery should be considered. Twenty-one patients with surgically confirmed NF were compared to 12 patients with superficial soft tissue infection. At admission, patients with NF were more likely to have skin areas of ischaemia or necrosis, fluid-filled vesicles, and severe sepsis or septic shock.

Since 1992, epidemiological and clinical studies have classified severe infections into three categories: sepsis, severe sepsis and septic shock. Microbiological documentation is not always provided. We used a different approach, focusing on the infection itself, whether or not it is microbiologically documented or associated with sepsis. In an international prospective cohort study, all patients admitted to the participating units from May 1997 to May 1998 were followed until hospital discharge. Twenty-eight intensive care units (ICU) in eight countries enrolled 14,364 patients. Of these, 6011 stayed in the ICU for less than 24 hours and 8353 for more than 24 hours. Overall, 3034 infectious episodes were recorded at ICU admission (crude incidence rate 21.1%). Among patients hospitalized for more than 24 hours, 1581 infectious episodes occurred in the ICU (crude incidence rate 18.9%), including 713 cases (45%) in patients who were already infected at ICU admission. These rates varied among the ICUs. Respiratory, gastrointestinal, urinary tract and primary bloodstream infections represented about 80% of all infections. Hospital-acquired and Intensive Care Unit-acquired infections were more frequently microbiologically documented than community-acquired infections (71% and 86%, respectively, vs 55%). About 28% of all infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock (18% were not classified). Crude in-hospital mortality rates ranged from 16.9% in uninfected patients to 53.6% in patients who were both infected at the time of ICU admission and subsequently acquired an infection during the ICU stay. The in-hospital mortality rate increased with severity, from 20% for sepsis to 40% for severe sepsis and 60% for septic shock, but also depended on the origin of infection (community vs hospital/ICU). Crude incidence rates of ICU infection were high, varying among ICUs and patient subsets. Thus, vital outcome depends not only on the severity of sepsis but also on the characteristics of the infection.

Objective: To document the costs and outcomes of the various forms of the septic syndromes [systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock), particularly those associated with infection acquired in an intensive care unit (ICU)., Design: Prospective data collection for all septic patients admitted to a medical ICU during a 1-year period. Costs were computed from the viewpoint of the hospital., Results: Mean total hospital costs were Euro 26,256, Euro 35,185, and Euro 27,083 for patients with sepsis, severe sepsis, and septic shock, respectively. Total costs varied slightly according to the site of infection and the severity of sepsis but were influenced mostly by its mode of acquisition: patients having sepsis associated with ICU-acquired infection incurred total costs about three times those of patients presenting with infection and sepsis on ICU admission (from Euro 39,908 in patients with ICU acquired sepsis to Euro 44,851 in patients with ICU-acquired septic shock). Stratifying patients by the presence of ICU-acquired infection also showed that a first episode of infection complicated by ICU-acquired sepsis incurred at least 2.5 times more costs than a single episode of sepsis., Conclusions: In this series the medical costs of sepsis were not markedly influenced by its severity but by its mode of acquisition. Due to wide variations in ICU costs cost-effectiveness analyses of treatments for sepsis should document the case-mix of patients and the contribution to this of nosocomial infections.

Objectives: To examine the incidence of infections and to describe them and their outcome in intensive care unit (ICU) patients., Design and Setting: International prospective cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge., Patients: A total of 14,364 patients were admitted to the ICUs, 6011 of whom stayed less than 24 h and 8353 more than 24 h., Results: Overall 3034 infectious episodes were recorded at ICU admission (crude incidence: 21.1%). In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes (crude incidence: 18.9%) including 713 (45%) in patients already infected at ICU admission. These rates varied between ICUs. Respiratory, digestive, urinary tracts, and primary bloodstream infections represented about 80% of all sites. Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections (71% and 86%, respectively vs. 55%). About 28% of infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock, and 18% were not classified. Crude hospital mortality rates ranged from 16.9% in non-infected patients to 53.6% in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay., Conclusions: The crude incidence of ICU infections remains high, although the rate varies between ICUs and patient subsets, illustrating the added burden of nosocomial infections in the use of ICU resources.

Objective: To evaluate the capacity and willingness of French-speaking patients to designate a surrogate within 24 h of their ICU admission. French laws fail to indicate what should be done when an otherwise legally competent patient transiently loses his decision-making capacity., Design: Surrogate designation was prospectively evaluated during two study periods. Only conscious patients were assessed using the Glasgow Come Score in the first study period, and all admitted patients were assessed in the second period. Decision-making capacity was evaluated using the Mini Mental Status Examination (MMSE) in the second study period., Setting: Twenty six-bed intensive care unit (ICU) in a French teaching hospital., Patients and Participants: Over a 8-month period 495 patients were included in the study, 415 in the first study period and 80 in the second., Measurements and Results: Of the 495 patients 185 (37.3%) were interviewed, and 62.7% designated a surrogate. The surrogate was the spouse in 50% of cases and a child in 28.4%. Only 25.8% were considered to have decision-making capacity; 78.1% of competent patients and 28% of the patients without decision-making capacity agreed to designate a surrogate., Conclusions: Surrogate designation by a patient should be evaluated in the light of the decision-making capacity of the patient. The traditional French paternalism still practiced by many French physicians appears out of tune with the wishes of their patients. We suggest that there is a need for developing a simple and effective tool for assessing decision-making capacity in ICU patients.

Context: Despite the success of some countries in controlling endemic methicillin-resistant Staphylococcus aureus (MRSA), such programs have not been implemented for some hospitals with endemic infection because of concerns that these programs would be costly and of limited benefit., Objective: To compare the costs and benefits of an MRSA control program in an endemic setting., Design and Setting: Case-control study conducted at a medical intensive care unit (ICU) of a French university hospital with a 4% prevalence of MRSA carriage at ICU admission., Patients: Twenty-seven randomly selected patients who had ICU-acquired MRSA infection between January 1993 and June 1997, matched to 27 controls hospitalized during the same period without MRSA infection., Main Outcome Measures: Intensive care unit costs attributable to MRSA infection, computed from excess therapeutic intensity in cases using estimates from a cost model derived in the same ICU, were compared with costs of the control program, derived from time-motion study of nurses and physicians. The threshold for MRSA carriage that would make the control strategy dominant was determined; sensitivity analyses varied rates of MRSA transmission and ratio of infection to transmission, length of ICU stay, and costs of isolation precautions., Results: The mean cost attributable to MRSA infection was US $9275 (median, $5885; interquartile range, $1400-$16,720). Total costs of the control program ranged from $340 to $1480 per patient. A 14% reduction in MRSA infection rate resulted in the control program being beneficial. In sensitivity analyses, the control strategy was dominant for a prevalence of MRSA carriage on ICU admission ranging from 1% to 7%, depending on costs of control measures and MRSA transmission, for infection rates greater than 50% following transmission., Conclusions: In this example of a hospital with endemic MRSA infection, selective screening and isolation of carriers on ICU admission are beneficial compared with no isolation.

Objectives: To compare the variations in intensive care (ICU) outcome in relation to variations in resources utilization and costs between a developed and a developing country with different medical and economical conditions., Design and Setting: Prospective comparison between a 26-bed French ICU and an 8-bed Tunisian ICU, both in university hospitals., Patients: Four hundred thirty and 534 consecutive admissions, respectively, in the French and Tunisian ICUs., Measurements: We prospectively recorded demographic, physiologic, and treatment information for all patients, and collected data on the two ICU structures and facilities. Costs and ICU outcome were compared in the overall population, in three groups of severity indexes and among selected diagnostic groups., Results: Tunisian patients were significantly younger, were in better health previously and were less severely ill at ICU admission (p < 0.01). French patients had a lower overall mortality rate (17.2 vs 22.5%; p < 0.01) and received more treatment (p < 0.01). In the low severity range, the outcome and costs were similar in the two countries. In the highest severity range, Tunisian and French patients had similar mortality rates, while the former received less therapy throughout their ICU stays (p < 0.05). Conversely, in the mid-range of severity, mortality was higher among Tunisian patients, and a difference in management was identified in COPD patients., Conclusion: Although the Tunisian ICU might appear more cost-effective than the French one in the highest severity group of patients, most of this difference appeared in relation to shorter lengths of ICU stay, and a poorer efficiency and cost-effectiveness was suggested in the mid-range severity group. Differences in economical constraints may partly explain differences in ICU performances. These results indicate where resource allocation could be directed to improve the efficiency of ICU care.

ICUs are often viewed as the epicenter of bacterial resistance. Overuse of antibiotics is one factor associated with this characteristic; other such factors include overcrowding, suboptimal observance of hygienic practices, cross-transmission of resistant strains, and high susceptibility of patients housed in ICUs. Evidence is scarce that different approaches to diagnosing infections, especially of the lower respiratory tract, can influence overall patterns of antibiotic usage and resistance. However, it is likely that more antibiotics are being administered to patients with suspected respiratory tract infections when diagnosed using nonspecific techniques than when more specific techniques are being used routinely. Additionally, the evidence is mounting that prior antibiotic usage is associated with increased risk of lower respiratory tract infection (LRTI), and also of infection caused by high-risk antibiotic-resistant pathogens, which in turn are associated with higher risk of treatment failure and mortality than their susceptible counterparts. A logical approach that may partially resolve this problem is to use specific diagnostic techniques, which will result in avoiding overtreating patients with suspected LRTI.

Objective: To examine the incidence, risk factors, and outcome of severe sepsis in intensive care unit (ICU) patients., Design and Setting: Inception cohort study from a 2-month prospective survey of 11,828 consecutive admissions to 170 adult ICUs of public hospitals in France., Patients: Patients meeting clinical criteria for severe sepsis were included and classified as having documented infection (ie, documented severe sepsis, n = 742), or a clinical diagnosis of infection without microbiological documentation (ie, culture-negative severe sepsis, n = 310)., Main Outcome Measures: Hospital and 28-day mortality after severe sepsis., Results: Clinically suspected sepsis and confirmed severe sepsis occurred in 9.0 (95% confidence interval [CI], 8.5 to 9.5) and 6.3 (95% CI, 5.8 to 6.7) of 100 ICU admissions, respectively. The 28-day mortality was 56% (95% CI, 52% to 60%) in patients with severe sepsis, and 60% (95% CI, 55% to 66%) in those with culture-negative severe sepsis. Major determinants of both early (< 3 days) and secondary deaths in the whole cohort were the Simplified Acute Physiology Score (SAPS) II and the number of acute organ system failures. Other risk factors for early death included a low arterial blood pH (< 7.33) (P < .001) and shock (P = .03), whereas secondary deaths were associated with the admission category (P < .001), a rapidly or ultimately fatal underlying disease (P < .001), a preexisting liver (P = .01) or cardiovascular (P = .002) insufficiency, hypothermia (P = .02), thrombocytopenia (P = .01), and multiple sources of infection (P = .02). In patients with documented sepsis, bacteremia was associated with early mortality (P = .03)., Conclusions: Only three of four patients presenting with clinically suspected severe sepsis have documented infection. However, patients with clinically suspected sepsis but without microbiological documentation and patients with documented infection share common risk factors and are at similarly high risk of death. In addition to the severity of illness score, acute organ failures and the characteristics of underlying diseases should be accounted for in stratification of patients and outcome analyses.

Topical antimicrobials may complement traditional infection control measures and hasten the control of an outbreak. When a suitable nonabsorbable antimicrobial regimen can be found, its use during outbreaks caused by Enterobacteriaceae colonizing the digestive tract appears especially attractive, whether the infection occurs via primary endogenous colonization or exogenous colonization. In the latter circumstance, however, topical antimicrobials are not a substitute for isolation precautions and careful handwashing, which remain insufficiently adhered to in ICUs. Topical antimicrobials should be used as part of a global strategy in which isolation precautions remain of primary importance. It is likely, but unproven by well-designed studies, that nasal decontamination of patient carriers during outbreaks due to methicillin-resistant Staphylococcus aureus can be useful to control the outbreak. In this instance, however, skin and wound disinfection appears as an essential complementary measure, and careful attention should be given to extranasal sites of colonization with MRSA, where resistance to the topical agent can emerge. Whatever the circumstances and setting, prolonged use of topical antimicrobials during protracted outbreaks is less effective and carries a major risk of resistance to the topical agent(s) used against the outbreak strains. In such circumstances, careful microbiologic monitoring of colonization is mandatory.

Study Objective: To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae, and to examine its effects on endemic nosocomial infection rates., Design: A 10-week prospective incidence study (group 1), and then an 8-week randomized, open trial of intestinal decontamination (groups 2 and 3)., Setting: A medical intensive care unit of a tertiary care university hospital., Patients: Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2; 124 patients were included in group 1, 50 in group 2 (control), and 36 in group 3 (intestinal decontamination)., Interventions: Neomycin, polymyxin E, and nalidixic acid were given to group 3 patients throughout their stay in the unit., Measurements and Main Results: Intestinal colonization with multiresistant strains occurred in 19.6% of patients in group 1, at a mean of 16 days after admission, and preceded detection in clinical samples by a mean of 11 days. During the decontamination trial, intestinal colonization rates decreased to 10% (group 2), and 3% (group 3) (P = 0.12 and P less than 0.01, compared with group 1, respectively). Corresponding infection rates were 9% (group 1), 3% (group 2), and 0 (group 3). No new cases were detected in the following 4 months. The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 (P less than 0.001). The overall rate of nosocomial infections was at 28% (group 1), 33% (group 2), and 32% (group 3)., Conclusions: Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit, but should not be recommended for routine prevention of endemic nosocomial infections.

Age, previous health status (HS), and severity of acute illness were assessed prospectively on 228 unselected patients admitted over 1 yr to the multidisciplinary ICU, to determine their influence on outcome. One hundred and fifty patients (66%) were discharged from the ICU, but the survival rate fell to 50% at 6 months, and was similar after 1 yr (49%). Over a 6-month period, there was improved HS in survivors which gradually leveled off. Compared to prior HS, the final HS was worsened in 37% of survivors. Three factors were important predictors of late survival: age under 50, good previous HS, and less than two visceral failures. We conclude that evaluation of ICU outcome should provide information on 6-month survival and HS and include important variables as age, previous HS, and severity of acute illness.