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Background: A study based on 2007 data estimated that 386,000 infections due to multidrug-resistant bacteria (MDRB) occurred in Europe that year and 25,000 patients died from these infections. Our objective was to estimate the morbidity and mortality associated with these infections in France. Methods: The MDRB considered were methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci, third-generation cephalosporin-resistant (3GC-R) Escherichia coli and Klebsiella pneumoniae, carbapenemresistant Klebsiella pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa (CR P. aeruginosa). The number of invasive infections (infections with bacteria isolated from blood or cerebrospinal fluid) due to MDRB, as reported by France to EARS-Net in 2012, was corrected for the coverage of our surveillance network and extrapolated to other body sites using ratios from the French healthcare-associated infections point prevalence survey and the literature. Mortality associated with MDRB infection was estimated using proportions from the literature. Methods and parameters were reviewed by a panel of experts. Results: We estimate that 158,000 (127,000 to 245,000) infections due to MDRB occurred in 2012 in France (incidence: 1.48 to 2.85 per 1000 hospital days), including 16,000 invasive infections. MRSA, 3GC-R E. coli and K. pneumoniae were responsible for 120,000 (90,000 to 172,000) infections, i.e., 75% of the total. An estimated 12,500 (11,500 to 17,500) deaths were associated with these infections, including 2,700 associated with invasive infections. MRSA, 3GC-R E. coli and CR P. aeruginosa accounted for 88% of these deaths. Conclusion: These first estimates confirm that MRSA, 3GC-R Escherichia coli and Klebsiella pneumoniae account for the largest portion of the morbidity and mortality of infections due to MDRB in France. These results are not directly comparable with the European study because the methodology used differs in many respects. The differences identified between our study and previous studies underline the need to define a standardised protocol for international assessments of the morbidity and mortality of antibiotic resistance. Estimating morbidity and mortality will facilitate communication and awareness in order to reinforce adherence and support of healthcare professionals and policy-makers to MDRB prevention programs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Objective: Ten years ago 8.4% of patients in French intensive care units (ICUs) were found to have severe sepsis or shock and 56% died in the hospital. As novel therapies for severe sepsis are emerging, updated epidemiological information is required.Design and Setting: An inception cohort study conducted in 206 ICUs of randomly selected hospitals over a 2-week period in 2001, including all patients meeting criteria for clinically or microbiologically documented severe sepsis (with > or =1 organ dysfunction).Measurements and Results: Among 3738 admissions, 546 (14.6%) patients experienced severe sepsis or shock, of which 30% were ICU-acquired. The median age of patients was 65 years, and 54.1% had at least one chronic organ system dysfunction. The median (range) Simplified Acute Physiology Score (SAPS II) and Sequential Organ Failure Assessment (SOFA) at onset of severe sepsis were 48 (2-129) and 9 (1-24), respectively. Mortality was 35% at 30 days; at 2 months the mortality rate was 41.9%, and 11.4% of patients remained hospitalized. The median (range) hospital stay was 25 (0-112) days in survivors and 7 (0-90) days in non-survivors. Chronic liver and heart failure, acute renal failure and shock, SAPS II at onset of severe sepsis and 24-h total SOFA scores were the independent risk factors most strongly associated with death.Conclusions: Although the attack rate of severe sepsis in French ICUs appears to have increased over the past decade, its associated mortality has decreased, suggesting improved management of patients. Severe sepsis incurs considerable resources use, and implementation of effective management strategies and continued research efforts are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the impact of the pandemic and post-pandemic periods on hospital admissions for LRTI, with a focus on patients with chronic respiratory disease (CRD)., Methods: From July 2013 to June 2023, monthly numbers of adult hospitalisations for LRTI (excluding SARS-CoV-2) were extracted from the French National Hospital Discharge Database. They were modelled by regressions with autocorrelated errors. Three periods were defined: (1) early pandemic and successive lockdowns; (2) gradual lifting of restrictions and widespread SARS-CoV-2 vaccination; (3) withdrawal of restriction measures., Results: Pre-pandemic incidence was 96 (90.5 to 101.5) per 100,000 population. Compared with the pre-pandemic period, no more seasonality and significant reductions were estimated in the first two periods: -43.64% (-50.11 to -37.17) and -32.97% (-39.88 to -26.05), respectively. A rebound with a positive trend and a seasonal pattern was observed in period 3. Similar results were observed for CRD patients with no significant difference with pre-pandemic levels in the last period (-9.21%; -20.9% to 1.67%), albeit with differential changes according to the type of CRD., Conclusions: COVID-19 pandemic containment measures contributed to changes in LRTI incidence, with a rapid increase and return to a seasonal pattern after their lifting, particularly in patients with CRD., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexandre Sabaté-Elabbadi reports support for attending meeting from SOS Oxygène and LVL Medical outside the submitted work. Muriel Fartoukh reports grants from BioMérieux and personal fees from BioMérieux, Pfizer, SOS Oxygène and Fisher and Paykel outside the submitted work. Laurence Watier reports personal fees from Pfizer, Sanofi and Heva outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.

Objective: This study aims to provide a case definition of sepsis of presumed bacterial aetiology based on 10th revision of the International Classification of Diseases (ICD-10) codes, to assess trends in sepsis incidence and mortality between 2015 and 2019 in France, and to describe the characteristics of affected patients and hospital stays., Design: Nationwide, population-based, retrospective observational study., Setting: Metropolitan France between 2015 and 2019., Participants: Between 2015 and 2019, 1 224 433 patients with sepsis of presumed bacterial aetiology were selected from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d'Information) and were identified from corresponding ICD-10 codes for explicit sepsis or implicit sepsis., Main Outcomes Measures: Annual overall and age-specific and gender-specific incidence and 95% CI, as well as trends in sepsis incidence and mortality, were estimated. Comorbidities, length of hospital stay and outcomes were described., Results: The sex-standardised and age-standardised incidence per 100 000 (95% CI) increased from 357 (356.0 to 359.0) in 2015 to 403 (401.9 to 405.0) in 2019 and remained higher for males compared with females. Children under 1 year and patients over 75 years consistently had the highest incidence. The most common comorbidities were cancer and chronic heart failure. The median hospital length of stay was 12 days. Most patients came from home, but only half returned home after their hospital stay and approximately 15% were discharged to long-term care. In-hospital mortality was about 25% and declined along the study period., Conclusions: Medico-administrative databases can be used to provide nationwide estimates of the in-hospital burden of bacterial sepsis. The results confirm the high burden of sepsis in France. These data should be complemented by estimating the additional burden associated with fungal and viral infections during the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antibiotic resistance is increasing among urinary pathogens, resulting in worse clinical and economic outcomes. We analysed factors associated with antibiotic-resistant bacteria (ARB) in patients hospitalized for urinary tract infection, using the comprehensive French national claims database., Methods: Hospitalized urinary tract infections were identified from 2015 to 2017. Cases (due to ARB) were matched to controls (without ARB) according to year, age, sex, infection, and bacterium. Healthcare-associated (HCAI) and community-acquired (CAI) infections were analysed separately; logistic regressions were stratified by sex., Results: From 9460 cases identified, 6468 CAIs and 2855 HCAIs were matched with controls. Over a 12-months window, the risk increased when exposure occurred within the last 3 months. The following risk factors were identified: antibiotic exposure, with an OR reaching 3.6 [2.8-4.5] for men with CAI, mostly associated with broad-spectrum antibiotics; surgical procedure on urinary tract (OR 2.0 [1.5-2.6] for women with HCAI and 1.3 [1.1-1.6] for men with CAI); stay in intensive care unit > 7 days (OR 1.7 [1.2-2.6] for men with HCAI). Studied co-morbidities had no impact on ARB., Conclusions: This study points out the critical window of 3 months for antibiotic exposure, confirms the impact of broad-spectrum antibiotic consumption on ARB, and supports the importance of prevention during urological procedures, and long intensive care unit stays.

Antibiotic stewardship requires clear insight into antibiotic overuse and the syndromes that lead to prescription. The aim of this study was to estimate the proportion of antibiotic prescriptions attributable to acute lower respiratory tract infections (LRTIs) during the cold season. Using individual data from the French National Health Insurance (NHI) database, weekly time series were constructed of outpatient antibiotic (beta-lactams and macrolides) prescriptions between January 2010 and December 2017. Time series were also constructed of tenth edition of the International Classification of Diseases (ICD-10) discharge diagnoses from a national network of emergency departments (EDs), stratified by specific syndromes (pneumonia, bronchitis, bronchiolitis and influenza-like illness). The number of outpatient antibiotic prescriptions attributable to these syndromes during the cold season in France was modeled and estimated for the entire population, young children (≤5 years) and the elderly (≥75 years). LRTIs accounted for 40% (95% confidence interval [95% CI]: 29, 52) of outpatient antibiotic use during the cold season for the entire population, including 23% (95% CI: 13, 33) and 17% (95% CI: 13, 22) for bacterial and viral infections, respectively. In children and the elderly, viral LRTIs were the reason for 38% (95% CI: 31, 46) and 20% (95% CI: 16, 25) of outpatient antibiotic use, respectively (with bronchiolitis accountable for half of use in young children). In the entire population and in children, respectively, outpatient antibiotic overuse attributable to viral LRTIs was estimated to be 289 (95% CI: 221, 374) and 1588 (95% CI: 1295, 1922) prescriptions per 100 000 inhabitants per week. These results highlight the major role of viral infections in driving antibiotic prescriptions, particularly in young children., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Long-term health-related quality of life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated., Methods: This was a French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 intensive care units (ICUs) for PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, sex, and Simplified Acute Physiology Score II with septic shock survivors (unexposed group). HR-QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36) questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R), and the activity of daily living (ADL) and instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire., Results: Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 (interquartile range [IQR], 35-83) months and 44 (IQR, 35-72) months, respectively, of ICU discharge (P = .23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median, 47 [IQR, 36-53] vs 54 [IQR, 36-57]; P = .18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n = 12/37 [32%]) exhibited lower PCS (34 [IQR, 24-38] vs 52 [IQR, 42-56]; P = .001) and IADL scores (7 [IQR, 4-8] vs 8 [IQR, 7-8]; P = .021) compared with nonamputated patients., Conclusions: Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health., Clinical Trials Registration: NCT03216577., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Objective: Antimicrobial resistance (AMR) has become one of the biggest threats to global public health given its association with mortality, morbidity and cost of health care. However, little is known on the economic burden of hospitalization attributable to AMR from a public health insurance perspective. We assessed the excess costs to the French public health insurance system attributable to AMR infections in hospitals., Methods: Bacterial infectious disease-related hospitalizations were extracted from the National health data information system for all stays occurring in 2015. Bacterial infections, strains, and microbial resistance were identified by specific French ICD-10 codes. Information about health care expenditure, co-morbidities and demographic characteristics (i.e. gender, age) are provided. We used a matched case-control approach to determine the excess of reimbursements paid to stays with AMR compared to stays with an infection without resistance. Cases and controls were matched on gender, age, Charlson comorbidity index, category of infection, infection as principal diagnosis (two classes), microorganism and hospital status. The overall AMR cost was extrapolated to stays with AMR and excluded from the sample (multiple infections), and a second extrapolation was performed to consider stays with unknown resistance status., Results: The final sample included 52,921 matched-pairs (98.2% cases). Our results suggest that AMR overall cost reached EUR109.3 million in France with a mean of EUR1103 per stay; extrapolation to the entire database shows that the overall cost could potentially reach EUR287.1 million if all cases would be identified. The mean excess length of hospital stay attributable to AMR was estimated at 1.6 days., Conclusion: AMR causes substantial cost burden in France for the public health insurance. Our study confirms the need to reinforce programs to prevent AMR infection and thereby reduce their economic burden.

Massive use of antibiotics has led to increased bacterial resistance to these drugs, making infections more difficult to treat. Few studies have assessed the overall antimicrobial resistance (AMR) burden, and there is a paucity of comprehensive data to inform health policies. This study aims to assess the overall annual incident number of hospitalised patients with AMR infection in France, using the National Hospital Discharge database. All incident hospitalisations with acute infections in 2016 were extracted. Infections which could be linked with an infecting microorganism were first analysed. Then, an extrapolation of bacterial species and resistance status was performed, according to age class, gender and infection site to estimate the total number of AMR cases. Resistant bacteria caused 139 105 (95% CI 127 920-150 289) infections, resulting in a 12.3% (95% CI 11.3-13.2) resistance rate. ESBL-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the most common resistant bacteria (>50%), causing respectively 49 692 (95% CI 47 223-52 142) and 19 493 (95% CI 15 237-23 747) infections. Although assumptions are needed to provide national estimates, information from PMSI is comprehensive, covering all acute bacterial infections and a wide variety of microorganisms.

Background: Identifying the mechanisms involved in the pathogenesis of Alzheimer's disease (AD) remains crucially important. Chronic age-related low-grade inflammation is considered to be one such mechanism, although its causes are unclear. Lipopolysaccharide (LPS)-type endotoxins, a major component of the outer membrane of Gram-negative bacteria, are known as potent pro-inflammatory molecules. Therefore, we hypothesized that greater exposure to circulating LPS, potentially mediated by the inflammatory pathway, would be a key step of the onset of AD., Objective: The aim of this study was to investigate the link between plasma endotoxin-exposure, inflammation, and AD., Methods: Applying a nested case-control design, we evaluated the associations among baseline plasma endotoxin-exposure (assessed by measuring LPS-binding protein (LBP) and soluble cluster of differentiation-14 (sCD14) levels), inflammation (assessed by measuring interleukin-6 (IL6) levels), and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 incident cases of AD were matched with 424 controls without dementia with regard to age, gender, and education level., Results: After adjusting for a large set of confounders, including the use of anti-inflammatory drugs, only higher LBP levels were significantly associated with a 30% higher odds of developing AD over 12 years (OR 1.30, 95% CIs [1.07-1.59]), regardless of IL6 levels., Conclusion: This large case-control study provides preliminary results concerning plasma endotoxin-exposure among the elderly and suggests that higher LBP levels, an acute-phase reactant involved in the pro-inflammatory response to LPS, are associated with higher odds of developing AD.

Purpose: Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality., Methods: A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up)., Results: Among the 306 included patients, 126 (41.2%; 95% CI 35.6-46.9) died and 180 (58.8%; 95% CI 53.3-64.3) survived during the follow-up period [13 (3-24) days], including 51/180 patients (28.3%, 95% CI 21.9-35.5) who eventually required limb amputations, with a median number of 3 (1-4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR) = 1.03 (1.02-1.04); p < 0.001], lower leucocytes [HR 0.83 (0.69-0.99); p = 0.034] and platelet counts [HR 0.77 (0.60-0.91); p = 0.007], and arterial blood lactate levels [HR 2.71 (1.68-4.38); p < 0.001] were independently associated with hospital death, while a neck stiffness [HR 0.51 (0.28-0.92); p = 0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06-3.38); p = 0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis., Conclusion: Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation., Trials Registration: NCT03216577.

Purpose: Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+)., Methods: Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012., Results: The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46-74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival., Conclusions: The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

We report a patient with an unusual initial metabolic presentation of imported human rabies who became symptomatic within 2 weeks of returning from Mali to France. This is the single case of imported human rabies identified in France within the past 11 years and the first report of viral RNA in bronchial secretions., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

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.

Objectives: Necrotizing fasciitis (NF) are rare and severe soft tissue infections associated with a high mortality rate. In order to assess the management of NF in French-speaking intensive care units (ICUs), we conducted a survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR)., Study Design: Online self-administered survey., Methods: A link to an online survey was sent by email to 4620 anesthesiologists and/or intensivists and was available online from January to February 2014., Results: One hundred and seventy-five physicians (3.8%) who worked in 135 ICUs filled out the online survey. Among respondents, 42% reported having managed up to two patients with NF during the previous year; 59% and 72% of respondents reported not having a surgical and a medical specialist consultant, respectively. A delayed access to the operating room (OR) of more than 6hours was reported in 31% of cases and access to the OR was reported not to be routinely considered as a priority in 13% of cases. Only 17% of respondents reported that time to transfer to the OR was never a cause for delayed surgery. The main causes for delayed surgery were: delayed diagnosis (45%), delayed validation of surgical intervention (37%), and difficulty of access to the OR (8%). Finally, 83% of respondents estimated that creating dedicated multidisciplinary teams for managing NFs could lead to improving outcomes., Conclusion: This survey illustrates the heterogeneous management of NF in French-speaking ICUs and points out several logistical aspects that should be improved to reduce the time to the first surgical debridement., (Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

In 2009, following the occurrence of several outbreaks of carbapenemase-producing Enterobacteriaceae (CPE), a programme for controlling the spread of CPE was implemented in the 38 hospitals of the Assistance Publique-Hôpitaux de Paris, a 21,000-bed institution. This programme included recommendations to isolate, and screen for CPE, patients previously hospitalised abroad, and bundled measures to control cross transmission (barrier precautions, dedicated staff and screening of contact patients). From 2004 to 2012, 140 CPE index cases were identified, 17 leading to outbreaks. After application of the programme, in spite of an increase in the number of CPE index cases epidemiologically linked with a recent stay or hospitalisation abroad, the proportion of cases followed by outbreaks, which was 40% (4/10) before 2009, decreased to 10% (13/130) (p=0.02), and the proportion of secondary cases among all CPE cases decreased from 69% (22/32) to 23% (38/168), (p<0.001). The number of secondary cases varied significantly depending on the speed and strength of the measures implemented around the CPE index case: quick (within two days of patient admission at the hospital) setting of nursing staff dedicated to the patient, quick setting of simple barrier precautions, or delayed measures of control (p=0.001). A sustained and coordinated strategy can lead to control CPE at the level of a large regional multi-hospital institution in a country where CPE are at an emerging stage.

Objective: We determined the percentage of healthcare workers' (HCWs') hands contaminated with Clostridium difficile spores after caring for patients with C. difficile infection (CDI) and risk factors associated with contamination., Design: Prospective study., Setting: A French university hospital., Methods: We compared the hand contamination rate among HCWs caring for patients with CDI (exposed group; n = 66) with that among an unexposed group (n = 44). Spores of C. difficile were recovered from the hands of HCWs after rubbing their fingers and palms in alcohol shortly after patient care. Associations between hand contamination and HCW category, type (patient or environment), and risk level (high or low risk) of HCW contacts and their respective duration as well as use of gloves were analyzed by bivariate and multivariate analysis., Results: C. difficile spores were detected on 24% of HCWs' hands in the exposed group and on 0% in the unexposed group (P < .001). In the exposed group, logistic regression, which adjusted for high-risk contact (ie, exposure to fecal soiling), contact with the environment, and contact with or without use of gloves, revealed that high-risk contact (adjusted odds ratio [aOR] per 1 contact increment, 2.78; 95% confidence interval [CI], 1.42-5.45; P = .003) and at least 1 contact without use of gloves (aOR, 6.26; 95% CI, 1.27-30.78; P = .02) were independently associated with HCW hand contamination by C. difficile spores., Conclusions: Nearly one-quarter of HCWs have hands contaminated with C. difficile spores after routine care of patients with CDI. Hand contamination is positively associated with exposure to fecal soiling and lack of glove use.

Background: Failure of noninvasive ventilation (NIV) is common in patients with COPD admitted to the ICU for acute hypercapnic respiratory failure (AHRF). We aimed to assess the rate of NIV failure and to identify early predictors of intubation under NIV in patients admitted for AHRF of all origins in an experienced unit., Methods: This was an observational cohort study using data prospectively collected over a 3-year period after the implementation of a nurse-driven NIV protocol in a 24-bed medical ICU of a French university hospital., Results: Among 242 subjects receiving NIV for AHRF (P(aCO2) > 45 mm Hg), 67 had cardiogenic pulmonary edema (CPE), 146 had acute-on-chronic respiratory failure (AOCRF) (including 99 subjects with COPD and 47 with other chronic respiratory diseases), and 29 had non-AOCRF (mostly pneumonia). Overall, the rates of intubation and ICU mortality were respectively 15% and 5%. The intubation rates were 4% in CPE, 15% in AOCRF, and 38% in non-AOCRF (P < .001). After adjustment, non-AOCRF was independently associated with NIV failure, as well as acidosis (pH < 7.30) and severe hypoxemia (P(aO2)/F(IO2) ≤ 200 mm Hg) after 1 hour of NIV initiation, whereas altered consciousness on admission and ventilatory settings had no influence on outcome., Conclusions: With a nurse-driven NIV protocol, the intubation rate was reduced to 15% in patients receiving NIV for AHRF, with a mortality rate of only 5%. Whereas the risk of NIV failure is associated with hypoxemia and acidosis after initiation of NIV, it is also markedly influenced by the presence or absence of an underlying chronic respiratory disease.

Background: Little is known about the incidence of and risk factors for adverse effects from endotracheal suctioning. We studied the incidence and risk factors, and evaluated the effect of suctioning practice guidelines., Methods: During a 3-month period, in 79 mechanically ventilated subjects, we recorded the adverse effects in 4,506 suctioning procedures. Then practice guidelines were implemented, and 1 year later, during another 3-month period, in 68 subjects, we recorded the adverse effects in 4,994 suctioning procedures., Results: In the first period, adverse effects occurred frequently: oxygen desaturation in 46.8% of subjects and 6.5% of suctionings, hemorrhagic secretions in 31.6% of subjects and 4% of suctionings, blood pressure change in 24.1% of subjects and 1.6% of suctionings, and heart rate change in 10.1% of subjects and 1.1% of suctionings. After guidelines implementation, all complications, both separately and all together, were reduced. The incidence of all complications together decreased from 59.5% to 42.6% of subjects, and from 12.4% to 4.9% of procedures (both P < .05). PEEP > 5 cm H2O was an independent risk factor for oxygen desaturation. Receiving > 6 suctionings per day was a risk factor for desaturation and hemorrhagic secretions. The use of guidelines was independently associated with fewer complications., Conclusions: Endotracheal suctioning frequently induces adverse effects. Technique, suctioning frequency, and higher PEEP are risk factors for complications. Their incidence can be reduced by the implementation of suctioning guidelines.

Purpose: Pulmonary vascular dysfunction is common during acute respiratory distress syndrome (ARDS), but there is controversy concerning prevalence and prognosis of cor pulmonale during protective ventilation for ARDS., Methods: This was a prospective observational study in an academic medical intensive care unit in France. Two hundred and twenty-six consecutive patients with moderate to severe ARDS (Berlin definition) ventilated with plateau pressure limited at 30 cmH₂O (mean PEEP of 8.8 ± 3.6 cmH₂O) underwent transesophageal echocardiography (TEE) within the first 3 days after the diagnosis of ARDS. Cor pulmonale was defined as a dilated right ventricle associated with septal dyskinesia., Results: Cor pulmonale was detected in 49 patients (prevalence of 22%; 95% confidence interval, 16-27%). Multivariate logistic regression identified infectious causes of lung injury and higher driving pressures as independent factors associated with cor pulmonale. Patients with cor pulmonale exhibited a higher incidence of shock (need for vasoactive drug) at the time of TEE and were more often managed with prone positioning and/or nitric oxide as adjunctive therapy for severe hypoxemia during ARDS course. The 28-day mortality rate was significantly higher in the group with cor pulmonale (60 vs. 36%, p < 0.01). Multivariate logistic regression identified McCabe and Jackson class, lung injury not related to pneumonia, aspiration, or sepsis, lactic acidosis, driving pressure, and cor pulmonale as independent risk factors for 28-day mortality., Conclusion: Cor pulmonale occurrence is not negligible in ARDS patients ventilated with airway pressure limitation. Cor pulmonale was associated with sepsis and higher values of driving pressure and was an independent risk factor for 28-day mortality in our series.

The international project MOSAR was conducted in five rehabilitation centers; patients were screened for rectal carriage of extended-spectrum β-lactamase (ESBL)-producing members of the Enterobacteriaceae. Among 229 Klebsiella pneumoniae isolates, four clonal groups (CG) or complexes (CC) prevailed: CG17 in France, CG101 in Italy, CG15 in Spain, and CC147 in Israel. ESBLs, mainly CTX-Ms, were produced by 226 isolates; three isolates expressed AmpC-like cephalosporinases. High genetic diversity of K. pneumoniae populations was observed, with specific characteristics at each center.

Objective: To describe the course and management of a protracted outbreak after intercontinental transfer of 2 patients colonized with multidrug-resistant Acinetobacter baumannii (MDRAB)., Design: An 18-month outbreak investigation., Setting: An 860-bed university hospital in France., Patients: Case patients (ie, carriers) were those colonized or infected with an MDRAB isolate., Methods: During the epidemic period, all intensive care unit (ICU) patients and contacts of carriers who were transferred to wards were screened for MDRAB carriage. Contact precautions, environmental screening, and auditing of healthcare worker (HCW) practices were implemented; rooms were cleaned with hydrogen peroxide mist disinfection. One ICU, in which most of the cases occurred, was closed on 4 occasions for thorough cleaning and disinfection., Results: The 2 index case patients were identified as 2 patients who carried the same MDRAB strain and who were admitted to the hospital after repatriation from Tahiti 5 months apart. During an 18-month period, a total of 84 secondary cases occurred. Reintroduction of MDRAB into the ICUs occurred from patients previously colonized or from healthcare personnel. Termination of the outbreak was only achieved when all carriers from wards or the ICU were cohorted to an isolation unit with dedicated healthcare personnel., Conclusions: Intercontinental transfer of carriers of MDRAB can result in extensive outbreaks and serious disruption of the hospital's organization. Transmission from carriers most likely occurred via the hands of HCWs, poor cleaning protocols, airborne spread, and contaminated water from sink traps. This protracted outbreak was controlled only after implementation of an extensive control program and eventual cohorting of all carriers in an isolation unit with dedicated healthcare personnel.

Purpose: The changed epidemiology of extended spectrum beta-lactamases (ESBL), the spread to the community and the need for prudent use of carbapenems require updated knowledge of risk factors for colonization with ESBL-producing enterobacteriaceae (ESBL-PE)., Methods: An 8-month prospective study in the medical ICU of an 850-bed general and university-affiliated hospital., Results: Of 610 patients admitted, 531 (87 %) had a rectal swab obtained at admission, showing a 15 % (82 patients) ESBL-PE carriage rate, mostly of E. coli (n = 51, 62 %); ESBL-PE caused 9 (3 %) infections on admission. By multivariable analysis, transfer from another ICU (OR = 2.56 [1, 22]), hospital admission in another country [OR = 5.28 (1.56-17.8)], surgery within the past year [OR = 2.28 (1.34-3.86)], prior neurologic disease [OR = 2.09 (1.1-4.0)], and prior administration of third generation cephalosporin (within 3-12 months before ICU admission) [OR = 3.05 (1.21-7.68)] were independent predictive factors of colonization by ESBL-PE upon ICU admission. Twenty-eight patients (13 % of those staying for more than 5 days) acquired ESBL carriage in ICU, mostly with E. cloacae (n = 13, 46 %) and K. pneumoniae (n = 10, 36 %). In carriers, ESBL-PE caused 10 and 27 % of first and second episodes of ICU-acquired infections, respectively., Conclusion: We found a high prevalence of ESBLE-PE colonization on admission to our ICU, even in the subgroup admitted from the community, but few first infections. Identifying risk factors for ESBL-PE colonization may help identifying which patients may warrant empiric ESBL-targeted antimicrobial drug therapy as a means to limit carbapenem use.

Background: No data on long-term outcomes of survivors of 2009 influenza A(H1N1) (A[H1N1])-associated ARDS are available. The objective of this study was to compare the 1-year outcomes of survivors of A(H1N1)-associated ARDS, according to use or no use of extracorporeal lung assist (ECLA), using its need as an ARDS severity surrogate., Methods: Survivors of ARDS (12 with ECLA use vs 25 without, corresponding to 75% and 54% of the eligible patients for each group, respectively) selected from the Réseau Européen de Ventilation Artificielle (REVA) registry had previously been healthy, with only pregnancy and/or moderate obesity (BMI ≤ 35 kg/m²) as known risk factors for A(H1N1) infection. Lung function and morphology, health-related quality of life (HRQoL), and psychologic impairment were evaluated., Results: At 1 year post-ICU discharge for the ECLA and no-ECLA groups, respectively, 50% and 40% reported significant exertion dyspnea, 83% and 64% had returned to work, and 75% and 64% had decreased diffusion capacity across the blood-gas barrier, despite their near-normal and similar lung function test results. For both groups, exercise test results showed diminished but comparable exercise capacities, with similar alveolar-arterial oxygen gradients at peak exercise, and CT scans showed minor abnormal findings. HRQoL assessed by the 36-Item Short-Form Health Survey was poorer for both groups than for a sex- and age-matched general population group, but without between-group differences. ECLA and no-ECLA group patients, respectively, had symptoms of anxiety (50% and 56%) and depression (28% and 28%) and were at risk for posttraumatic stress disorder (41% and 44%)., Conclusions: One year post-ICU discharge, a majority of survivors of A(H1N1)-associated ARDS had minor lung disabilities with diminished diffusion capacities across the blood-gas barrier, and most had psychologic impairment and poorer HRQoL than a sex- and age-matched general population group. ECLA and no-ECLA group patients had comparable outcomes., Trial Registry: ClinicalTrials.gov; No.: NCT01271842; URL: www.clinicaltrials.gov

Assistance Publique-Hôpitaux de Paris launched a specific strategy to survey and control the spread of emerging multidrug-resistant bacteria such as carbapenemase-producing Enterobacteria (CPE). Among the 63 CPE events that occurred between 2004 and 2011, 87% involved patients with a link with cross-border exchanges, justifying the recommendation to screen and isolate such patients., (© 2012 International Society of Travel Medicine.)

Repeated outbreaks of vancomycin-resistant Enterococcus faecium (VRE) occurred between 2004 and 2010 in Assistance Publique--Hôpitaux de Paris (AP-HP), a 23,000-bed multi-hospital institution. From August 2004 to December 2005, the French guidelines for preventing cross-transmission of multiresistant bacteria were applied. Because the number of VRE cases continued to increase, an institutional control programme was implemented from January 2006 onwards: it foresees stopping transfer of VRE and contact patients, separating VRE and contact patients in distinct cohorts, intervention of a central infection control team to support local teams, and quick application of measures as soon as first VRE cases are identified. Between August 2004 and December 2010, 45 VRE outbreaks occurred in 21 of the 38 AP-HP hospitals, comprising 533 cases. Time series analysis showed that the mean number of cases increased by 0.8 cases per month (95% confidence interval (CI): 0.3 to 1.3, p=0.001) before, and decreased by 0.7 cases per month after implementation of the programme (95% CI: -0.9 to -0.5, p<0.001), resulting in a significant trend change of -1.5 cases per month (95% CI: -2.1 to -0.9, p<0.001). The number of cases per outbreak was significantly lower after implementation of the programme. A sustained and coordinated strategy can control emerging bacteria at the level of a large regional multihospital institution.

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.

In France, the surveillance of hospitalized cases of pandemic influenza was implemented in July 2009 and restricted to intensive-care unit (ICU) patients in November. We described the characteristics of the 1065 adult patients admitted to ICUs and analysed risk factors for severe outcome (mechanical ventilation or death). Eighty-seven percent of cases were aged 15-64 years. The case-fatality ratio was 20%. The risk for severe outcome increased with age and obesity while this association was negative for chronic respiratory disease. Late antiviral therapy was associated with a severe outcome in ICU patients with risk factors (adjusted OR 2·0, 95% CI 1·4-3·0). This study confirms the considerable contribution of young adults to A(H1N1) 2009 mortality. It shows the role of obesity as an independent risk factor for severe disease, and of early antiviral therapy as a protective factor, at least in patients with risk factors.

Rationale: Despite their controversial role, corticosteroids are often administered to patients with adult respiratory distress syndrome (ARDS) secondary to viral pneumonia., Objectives: To analyze the impact of corticosteroid therapy on outcomes of patients having ARDS associated with influenza A/H1N1 pneumonia., Methods: Patients from the French registry of critically ill patients with influenza A/H1N1v 2009 infection were selected if fulfilling criteria for ARDS, excluding patients having other indication for corticosteroids, or decompensated underlying disease as the primary cause for intensive care unit admission. Survival to hospital discharge was analyzed using Cox regression, accounting for the time to administration of steroids, and after adjustment on the propensity for receiving steroid therapy., Measurements and Main Results: Of 208 patients with ARDS, 83 (39.9%) received corticosteroids (median initial dose of 270 mg equivalent hydrocortisone per day for a median of 11 d). Steroid therapy was associated with death, both in crude analysis (33.7 vs. 16.8%; hazard ratio, 2.4; 95% CI, 1.3-4.3; P = 0.004) and after propensity score-adjusted analysis (adjusted hazard ratio, 2.82; 95% CI, 1.5-5.4; P = 0.002), controlling for an admission severity Simplified Acute Physiology Score, version 3, greater than 50, initial administration of vasopressors, and immunodepression. Early therapy (≤ 3 d of mechanical ventilation) appeared more strongly associated with mortality than late administration. Patients receiving steroids had more acquired pneumonia and a trend to a longer duration of ventilation., Conclusions: Our study provides no evidence of a beneficial effect of corticosteroids in patients with ARDS secondary to influenza pneumonia, but suggests that very early corticosteroid therapy may be harmful.

Background: The Assistance Publique-Hôpitaux de Paris (AP-HP) institution administers 38 teaching hospitals (23 acute care and 15 rehabilitation and long-term care hospitals; total, 23 000 beds) scattered across Paris and surrounding suburbs in France. In the late 1980s, the proportion of methicillin resistance among clinical strains of Staphylococcus aureus (MRSA) reached approximately 40% at AP-HP., Methods: A program aimed at curbing the MRSA burden was launched in 1993, based on passive and active surveillance, barrier precautions, training, and feedback. This program, supported by the strong commitment of the institution, was reinforced in 2001 by a campaign promoting the use of alcohol-based hand-rub solutions. An observational study on MRSA rate was prospectively carried out from 1993 onwards., Results: There was a significant progressive decrease in MRSA burden (-35%) from 1993 to 2007, whether recorded as the proportion (expressed as percentage) of MRSA among S aureus strains (41.0% down to 26.6% overall; 45.3% to 24.2% in blood cultures) or incidence of MRSA cases (0.86 down to 0.56 per 1000 hospital days). The MRSA burden decreased more markedly in intensive care units (-59%) than in surgical (-44%) and medical (-32%) wards. The use of ABHR solutions (in liters per 1000 hospital days) increased steadily from 2 L to 21 L (to 26 L in acute care hospitals and to 10 L in rehabilitation and long-term care hospitals) following the campaign., Conclusion: A sustained reduction of MRSA burden can be obtained at the scale of a large hospital institution with high endemic MRSA rates, providing that an intensive program is maintained for a long period.

Objective: To describe the French program for the prevention of healthcare-associated infections and antibiotic resistance and provide results for some of the indicators available to evaluate the program. In addition to structures and process indicators, the 2 outcome indicators selected were the rate of surgical site infection and the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates among the S. aureus isolates recovered., Design: Descriptive study of the evolution of the national structures for control of healthcare-associated infections since 1992. Through national surveillance networks, process indicators were available from 1993 to 2006, surgical site infection rates were available from 1999 to 2005, and prevalence rates for MRSA infection were available from 2001 to 2007., Results: A comprehensive national program has gradually been set up in France during the period from 1993 to 2004, which included strengthening of organized infection control activities at the local, regional, and national levels and developing large networks for surveillance of specific infections and antibiotic resistance. These achievements were complemented by instituting mandatory notification for unusual nosocomial events, especially outbreaks. The second phase of the program involved the implementation of 5 national quality indicators with public reporting. Surgical site infection rates decreased by 25% over a 6-year period. In France, the median proportion of MRSA among S. aureus isolates recovered from patients with bacteremia decreased from 33.4% to 25.7% during the period from 2001 to 2007, whereas this proportion increased in many other European countries., Conclusions: Very few national programs have been evaluated since the Study on the Efficacy of Nosocomial Infection Control. Although continuing efforts are required, the French program appears to have been effective at reducing infection rates.

Background: Critically ill patients often require emergency intubation. The use of etomidate as the sedative agent in this context has been challenged because it might cause a reversible adrenal insufficiency, potentially associated with increased in-hospital morbidity. We compared early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients., Methods: In this randomised, controlled, single-blind trial, 655 patients who needed sedation for emergency intubation were prospectively enrolled from 12 emergency medical services or emergency departments and 65 intensive care units in France. Patients were randomly assigned by a computerised random-number generator list to receive 0.3 mg/kg of etomidate (n=328) or 2 mg/kg of ketamine (n=327) for intubation. Only the emergency physician enrolling patients was aware of group assignment. The primary endpoint was the maximum score of the sequential organ failure assessment during the first 3 days in the intensive care unit. We excluded from the analysis patients who died before reaching the hospital or those discharged from the intensive care unit before 3 days (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00440102., Findings: 234 patients were analysed in the etomidate group and 235 in the ketamine group. The mean maximum SOFA score between the two groups did not differ significantly (10.3 [SD 3.7] for etomidate vs 9.6 [3.9] for ketamine; mean difference 0.7 [95% CI 0.0-1.4], p=0.056). Intubation conditions did not differ significantly between the two groups (median intubation difficulty score 1 [IQR 0-3] in both groups; p=0.70). The percentage of patients with adrenal insufficiency was significantly higher in the etomidate group than in the ketamine group (OR 6.7, 3.5-12.7). We recorded no serious adverse events with either study drug., Interpretation: Our results show that ketamine is a safe and valuable alternative to etomidate for endotracheal intubation in critically ill patients, and should be considered in those with sepsis., Funding: French Ministry of Health.

Background: In developed countries at present, death mostly occurs in hospitals, but the circumstances and factors associated with the quality of organization and care surrounding death are not well described., Methods: We designed a large multicenter cross-sectional study to analyze the setting and clinical course of each patient on the day of death. We included 2750 clinical departments of 294 hospitals. Of these, 1033 departments (37.6%) of 200 hospitals (68.0%) contributed to the Mort-a-l'Hôpital survey. Data were collected prospectively by the bedside nurse of each patient within 10 days of the occurrence of death. Main outcome measures included circumstances of death in hospitalized patients; secondary outcomes, nurses' perceptions of quality of end-of-life care., Results: Of the 1033 participating departments, 420 recorded no deaths during the study period and 613 declared at least 1 death. In the 3793 patients who died and were included for assessment, only 925 (24.4%) had loved ones present at the time of death; 70.1% had respiratory distress during the period before death; and only 12.0% were in pain. Written protocols for end-of-life care were available in 12.2% of participating departments. Only 35.1% of nurses judged the quality of dying and death acceptable for themselves. Principal factors significantly associated with this perception were availability of a written protocol for end-of-life care, anticipation of death, informing the family, surrogate designation, adequate control of pain, presence of family or friends at the time of death, and staff meeting with the family after the death., Conclusions: This large prospective study identifies nonoptimal circumstances of death for hospitalized patients and a number of suggestions for improvement. A combination of factors reflected in the nurses' satisfaction may improve the quality of end-of-life care.

Rationale: Steady-state mild pulmonary hypertension is a risk factor for death in adults with sickle cell disease. Acute pulmonary hypertension has been reported during exercise and vasoocclusive pain crisis in these patients., Objectives: The aim of the present study was to evaluate changes in pulmonary pressures and cardiac biomarkers during severe acute chest syndrome and their associations with mortality., Methods: We prospectively evaluated 70 consecutive adults who received standardized treatment in our intensive care unit for a total of 84 episodes. At admission, cardiac biomarkers were measured. Transthoracic echocardiography was performed for pulmonary hypertension assessment via measurement of tricuspid regurgitant jet velocity and was repeated when possible after resolution., Measurements and Main Results: Tricuspid jet velocity was less than 2.5 m/second in 34 (40%) of the 84 episodes, 2.5 to 2.9 m/second in 19 (23%), and 3 m/second or greater in 31 episodes (37%). Cor pulmonale occurred in 11 (13%) episodes. Tricuspid jet velocity showed significant positive correlations with B-type natriuretic peptide (rho = 0.54, P < 0.01) and cardiac troponin I (rho = 0.42, P < 0.01). Pulmonary pressures increased compared with steady state then decreased after resolution. All five patients who required invasive ventilation and all four patients who died during the immediate hospital course had jet velocity values of 3 m/second or greater. Overall mortality was 12.9% (9 patients) and survival was significantly lower in patients whose jet velocity was 3 m/second or greater during at least one episode, compared with the other patients (P < 0.01)., Conclusions: Pulmonary pressures increase during severe acute chest syndrome, and pulmonary hypertension is associated with cardiac biomarker elevation and a higher risk of death.

Objective: The regulatory framework of clinical research in France was recently modified substantially, in part to transpose into French law directive 2001/20/EC of the European Parliament and Council, which concerns only drug trials. The revision also covered research on "human beings" (Public Health L. 2004-806, 2006-450), on biological samples (revision of bioethics, L. 2004-800) and on data (the so-called CNIL act, L. 2004-801). The value of this set of texts (statutes, decrees, and regulations) is that it diversifies and clarifies the different forms of clinical research., Methods: This article describes the painful progression of important public health studies, most often with "academic" sponsors., Results: The 5 studies described here managed to overcome a variety of obstacles posed by the pre-2004 regulations., Comments: To understand the new provisions, it is useful to recall the difficulties, imprecision and inaptness of the earlier regulations.

Background: The management of suspected ventilator-associated pneumonia (VAP) is traditionally based on either a clinical or a "bacteriological" approach. Direct examination of specimens may provide a valuable help to both approaches., Objective: The objective was to test an algorithm for the management of suspected pneumonia based on severity criteria and Gram stains of specimens, including early treatment of patients with a positive Gram stain of a protected telescoping catheter specimen and awaiting culture results in patients with either Gram stains of endotracheal aspirate and protected specimen both being negative, or only positive endotracheal aspirate (EA), except in the presence of the severity criteria., Methods: Observational study including 76 first episodes of suspected pneumonia in 4 units. We assessed the rates of correctly diagnosed episodes and of those treated empirically (i.e., ultimately confirmed pneumonia), or appropriately not receiving such therapy (non-confirmed pneumonia), based on protected specimen culture results., Results: When adhered to, the algorithm allowed early appropriate management in 80% of patients, including 83% of those with confirmed pneumonia, and 74% of those without confirmed infection. The rate of appropriately managed episodes using this algorithm was significantly higher than that using a strategy based on the modified clinical pulmonary infection score (CPIS) alone (80 vs. 50%, p<0.001). The empiric regimen was adequate in 86% of confirmed episodes., Conclusion: A strategy based on severity criteria and Gram stain examination of respiratory tract specimens allows correct identification and appropriate management of more than 80% of mechanically ventilated patients who need or do not need therapy for suspected pneumonia.

We describe a patient who suffered from an unusually severe form of neuromyelitis optica with a hyperacute time-course evolution requiring mechanical ventilation within 3 days. The patient died after 72 days and autopsy showed major spinal cord, optic nerve, and brainstem necrosis, and multifocal necrotic lesions on the cerebellum and cerebral white matter.

Internationally recognized definitions of septic syndromes are available and make it possible to conduct more homogenous clinical trials. Nearly 15% of patients in intensive care have severe sepsis, and two thirds of them septic shock. In France, it is estimated that approximately 75,000 patients with severe sepsis are admitted to intensive care units, and the frequency of sepsis is increasing. Hospital mortality is 20% for simple sepsis and 40% and higher for cases of severe sepsis or septic shock; it has nonetheless been improving over the past decade. Prognosis depends on the severity of organ dysfunctions, in particular, of cardiovascular failure. Early identification of sepsis and of patients at risk of developing septic shock, together with rapid intervention aiming especially to correct hemodynamic disorders, is likely to improve prognosis., ((c) 2006, Masson, Paris.)

Background: The indication of antiseptic-coated catheters remains debated., Objective: To test the ability of the new generation of chlorhexidine-silver and sulfadiazine-coated catheters, with enhanced antiseptic coating, to reduce the risk of central venous catheter (CVC)-related infection in ICU patients., Design: Multicentre randomized double-blind trial., Patients and Setting: A total of 397 patients from 14 ICUs of university hospitals in France., Intervention: Patients were randomized to receive an antiseptic-coated catheter (ACC) or a standard non-coated catheter (NCC)., Measurements: Incidence of CVC-related infection., Results: Of 367 patients having a successful catheter insertion, 363 were analysed (175 NCC and 188 ACC). Patients had one (NCC=162, ACC=180) or more (NCC=13, ACC=11) CVC inserted. The two groups were similar for insertion site [subclavian (64 vs 69)] or jugular (36 vs 31%)], and type of catheters (single-lumen 18 vs 18%; double-lumen 82 vs 82%), and mean (median) duration of catheterisation [12.0+/-11.7 (9) vs 10.5+/-8.8 (8) days in the NCC and ACC groups, respectively]. Significant colonisation of the catheter occurred in 23 (13.1%) and 7 (3.7%) patients, respectively, in the NCC and ACC groups (11 vs 3.6 per 1000 catheter-days; p=0.01); CVC-related infection (bloodstream infection) occurred in 10 (5) and 4 (3) patients in the NCC and CC groups, respectively (5.2 vs 2 per 1000 catheter days; p=0.10)., Conclusions: In the context of a low baseline infection rate, ACC were associated with a significant reduction of catheter colonisation and a trend to reduction of infection episodes, but not of bloodstream 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.

Several studies have pointed out ethical shortcomings in the decision-making process for withholding or withdrawing life-supporting treatments. We conducted a study to evaluate the perceptions of all caregivers involved in this process in the intensive care unit. A closed-ended questionnaire was completed by 3,156 nursing staff members and 521 physicians from 133 French intensive care units (participation rate, 42%). Decision-making processes were perceived as satisfactory by 73% of physicians and by only 33% of the nursing staff. More than 90% of caregivers believed that decision-making should be collaborative, but 50% of physicians and only 27% of nursing staff members believed that the nursing staff was actually involved (p < 0.001). Fear of litigation was a reason given by physicians for modifying information given to competent patients, families, and nursing staff. Perceptions by nursing staff may be a reliable indicator of the quality of medical decision-making processes and may serve as a simple and effective tool for evaluating everyday practice. Recommendations and legislation may help to build consensus and avoid conflicts among caregivers at each step of the decision-making process.

The prevalence of penicillin-nonsusceptible pneumococci is sharply divided between France (43%) and Germany (7%). These differences may be explained on different levels: antibiotic-prescribing practices for respiratory tract infections; patient-demand factors and health-belief differences; social determinants, including differing child-care practices; and differences in regulatory practices. Understanding these determinants is crucial for the success of possible interventions. Finally, we emphasize the overarching importance of a sociocultural approach to preventing antibiotic resistance in the community.

Objective: To identify the routes of transmission during an outbreak of infection with hepatitis C virus (HCV) genotype 2a/2c in a hemodialysis unit., Design: A matched case-control study was conducted to identify risk factors for HCV seroconversion. Direct observation and staff interviews were conducted to assess infection control practices. Molecular methods were used in a comparison of HCV infecting isolates from the case-patients and from patients infected with the 2a/2c genotype before admission to the unit., Setting: A hemodialysis unit treating an average of 90 patients., Patients: A case-patient was defined as a patient receiving hemodialysis with a seroconversion for HCV genotype 2a/2c between January 1994 and July 1997 who had received dialysis in the unit during the 3 months before the onset of disease. For each case-patient, 3 control-patients were randomly selected among all susceptible patients treated in the unit during the presumed contamination period of the case-patient., Results: HCV seroconversion was associated with the number of hemodialysis sessions undergone on a machine shared with (odds ratio [OR] per additional session, 1.3; 95% confidence interval [CI95], 0.9 to 1.8) or in the same room as (OR per additional session, 1.1; CI95, 1.0 to 1.2) a patient who was anti-HCV (genotype 2a/2c) positive. We observed several breaches in infection control procedures. Wetting of transducer protectors in the external pressure tubing sets with patient blood reflux was observed, leading to a potential contamination by blood of the pressure-sensing port of the machine, which is not accessible to routine disinfection. The molecular analysis of HCV infecting isolates identified among the case-patients revealed two groups of identical isolates similar to those of two patients infected before admission to the unit., Conclusions: The results suggest patient-to-patient transmission of HCV by breaches in infection control practices and possible contamination of the machine. No additional cases have occurred since the reinforcement of infection control procedures and the use of a second transducer protector.

Objective: A postinjury immunodepression involving neutrophil functions has been described in critically ill patients. The aim of this prospective study was to search for a relationship between an impairment of neutrophil functions and the subsequent development of nosocomial infection., Design: Twenty-one severely ill (simplified acute physiology score II >20 on admission), nonimmunosuppressed patients who were receiving no antibiotics active against methicillin-resistant Staphylococcus aureus and highly resistant Pseudomonas aeruginosa were included. Twelve healthy subjects constituted a control group., Measurements: Neutrophil functions (phagocytosis and bactericidal activity toward S. aureus and P. aeruginosa in homologous plasma, reactive oxygen species secretion) were studied at day 4 +/- 1 after admission, and occurrence of nosocomial infection was prospectively recorded over the following 5 days. Interleukin-10 concentration was assessed by enzyme-linked immunosorbent assay. Results are expressed as median (25th-75th percentiles)., Main Results: Six out of the 21 patients acquired a nosocomial infection during the 5 days after blood sampling (infected group). Compared with the patients who did not acquire nosocomial infection (noninfected group, n = 15), the neutrophils of the infected group demonstrated a higher percentage of intracellular bacterial survival (17% [2% to 67%] vs. infected: 62% [22% to 100%], p <.05), leading to an impairment of S. aureus killing in homologous plasma (killed bacteria: 4.93 log(10) colony forming units/mL [4.24-5.29] vs. infected: 3.62 log(10) colony forming units/mL [0.00-4.58], p <.05). Interleukin-10 plasma concentration was higher in infected patients (78 pg/mL [60-83]) compared with noninfected patients (22 pg/mL [14-58], p <.05). By contrast, P. aeruginosa killing was similar in patients whether or not they acquired a nosocomial infection., Conclusion: A decrease in S. aureus killing capabilities of neutrophils can be evidenced within the days before occurrence of a nosocomial infection.