Publications by authors named "Christian Brun-Buisson"

203 Publications

Costs and Outcomes of 1-year post-discharge care trajectories of patients admitted with infection due to antibiotic-resistant bacteria.

J Infect 2021 Feb 5. Epub 2021 Feb 5.

Epidemiology and Modeling of bacterial Evasion to Antibacterials Unit (EMEA), Institut Pasteur, Paris, France; Université Paris-Saclay, UVSQ, Inserm, CESP, 94807, Villejuif, France. Electronic address:

Background: The impact of antibiotic resistance (AMR) on initial hospital management has been extensively studied but its consequences after hospital discharge remain largely unknown. We aimed to analyze hospital care trajectories, cumulative length of hospital stays (c-LOS) and associated costs of care over a 1-year period after hospitalization with incident AMR infection.

Method: All incident bacterial infection-related hospitalizations occurring from January 1, 2015, to December 31, 2015 and recorded in the French national health data information system were extracted. Bacterial resistance ICD-10 codes determined six infection status. Inpatient and outpatient care consumption and associated costs were studied. The impact of resistance on c-LOS was estimated using a Poisson regression. A sequence analysis through optimal matching method was conducted to identify hospital trajectories along with an extrapolation.

Finding: Of the 73,244 patients selected, 15.9% had AMR infection, thus providing 58,286 incident AMR infections after extrapolation. c-LOS was significantly longer for infections with resistant bacteria, reaching 20.4 days and 2.9 additional days IC95%[2.6; 3.2] for skin and soft tissue infections. An estimated 29,793 (51.1%) patients had hospital readmission within the following year, for a total cost of €675 million. Five post-discharge trajectories were identified: Post-hospitalization mainly at home (68.4% of patients); Transition to home from rehabilitation care (12.3%); Early death (<3 months) (9.7%); Late death (7.4%), and Long-term hospitalization (2.2%).

Interpretation: AMR has an impact on patients' c-LOS stay beyond the initial hospitalization. Half of patients hospitalized due to AMR are readmitted to hospital within the ensuing year, along five different trajectories.

Funding: French Ministry of health.
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http://dx.doi.org/10.1016/j.jinf.2021.02.001DOI Listing
February 2021

Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease.

J Clin Med 2020 Nov 19;9(11). Epub 2020 Nov 19.

DHU A-TVB, Service de Médecine Intensive Réanimation, 51 Avenue du Maréchal de Lattre de Tassigny, AP-HP Hôpitaux Universitaires Henri Mondor, 94010 Créteil, France.

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before-after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 μg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14-18] vs. 13 [13,14] days ( = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% ( = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.
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http://dx.doi.org/10.3390/jcm9113718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699579PMC
November 2020

Quantifying risk of disease due to extended-spectrum β-lactamase producing Enterobacteriaceae in patients who are colonized at ICU admission.

J Infect 2020 05 4;80(5):504-510. Epub 2020 Mar 4.

AP-HP, Hôpitaux Universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, 51, Av de Lattre de Tassigny, Créteil 94010 France; Faculté de Médecine de Créteil, IMRB, GRC CARMAS, Université Paris Est Créteil, Créteil 94010, France; INSERM, Unité U955, Créteil F-94010, France. Electronic address:

Background: The prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) has globally increased and spread to the community. No clinical score is available to select carriers in whom these organisms can be empirically targeted at ICU admission.

Methods: We prospectively assessed between 2009 and 2017 the prevalence of ESBL-PE infection in carriers at ICU admission. A logistic regression was used to determine independent risk factors associated with ESBL-PE infection, and to build a clinical risk score.

Results: Of the 8,061 admissions over the study 7-year period, 745 (9%) patients were ESBL-PE carriers at admission, of whom 395 had infections at ICU admission including 59 (15%) who had culture-proven ESBL-PE related infection. By multivariable analysis, age >60 years, cirrhosis, being on broad-spectrum antibiotics within the past three months, urinary or intra-abdominal source of infection, and the absence of chronic pulmonary disease, were the five independent factors associated with ESBL-PE infection in carriers. A clinical risk score ranging from 0 to 7 was built based on these variables, with an area under the receiver operating characteristic curve (ROC) of 0.82 (95% CI 0.78-0.86); p <0.001. The prevalence of ESBL-PE infection for clinical risk scores of 0-1, 2-3, 4-5, or 6-7 was 0%, 4%, 26%, and 49%, respectively. The negative predictive value when Mondor ESBL risk score is <4 was 97%.

Conclusion: ESBL-PE related infection was not common in carriers at ICU admission. A clinical risk score may spare ESBL-PE carriers with lower risk of ESBL-PE infection at ICU admission unnecessary empiric carbapenem therapy.
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http://dx.doi.org/10.1016/j.jinf.2020.02.023DOI Listing
May 2020

Selective decontamination of the digestive tract (SDD) in critically ill patients: a narrative review.

Intensive Care Med 2020 02 9;46(2):343-349. Epub 2019 Dec 9.

Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Selective decontamination of the digestive tract (SDD) is an infection prevention measure for intensive care unit (ICU) patients that was proposed more than 30 years ago, and that is currently considered standard of care in the Netherlands, but only used sporadically in ICUs in other countries. In this narrative review, we first describe the rationale of the individual components of SDD and then review the evidence base for patient-centered outcomes, where we distinguish ICUs with low prevalence of antibiotic resistance from ICUs with moderate-high prevalence of resistance. In settings with low prevalence of antibiotic resistance, SDD has been associated with improved patient outcome in three cluster-randomized studies. These benefits were not confirmed in a large international cluster-randomized study in settings with moderate-to-high prevalence of antibiotic resistance. There is no evidence that SDD increases antibiotic resistance. We end with future directions for research.
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http://dx.doi.org/10.1007/s00134-019-05883-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042187PMC
February 2020

A multiplex analysis of sepsis mediators during human septic shock: a preliminary study on myocardial depression and organ failures.

Ann Intensive Care 2019 Jun 4;9(1):64. Epub 2019 Jun 4.

AP-HP, Service de Réanimation Médicale, Hôpitaux universitaires Henri Mondor, DHU A-TVB, 94010, Créteil, France.

Background: The mechanisms of organ failure during sepsis are not fully understood. The hypothesis of circulating factors has been suggested to explain septic myocardial dysfunction. We explored the biological coherence of a large panel of sepsis mediators and their clinical relevance in septic myocardial dysfunction and organ failures during human septic shock.

Methods: Plasma concentrations of 24 mediators were assessed on the first day of septic shock using a multi-analyte cytokine kit. Septic myocardial dysfunction and organ failures were assessed using left ventricle ejection fraction (LVEF) and the Sequential Organ Failure Assessment score, respectively.

Results: Seventy-four patients with septic shock (and without immunosuppression or chronic heart failure) were prospectively included. Twenty-four patients (32%) had septic myocardial dysfunction (as defined by LVEF < 45%) and 30 (41%) died in ICU. Hierarchical clustering identified three main clusters of sepsis mediators, which were clinically meaningful. One cluster involved inflammatory cytokines of innate immunity, most of which were associated with septic myocardial dysfunction, organ failures and death; inflammatory cytokines associated with septic myocardial dysfunction had an additive effect. Another cluster involving adaptive immunity and repair (with IL-17/IFN pathway and VEGF) correlated tightly with a surrogate of early sepsis resolution (lactate clearance) and ICU survival.

Conclusions: In this preliminary study, we identified a cluster of cytokines involved in innate inflammatory response associated with septic myocardial dysfunction and organ failures, whereas the IL-17/IFN pathway was associated with a faster sepsis resolution and a better survival.
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http://dx.doi.org/10.1186/s13613-019-0538-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548788PMC
June 2019

A Payer Perspective of the Hospital Inpatient Additional Care Costs of Antimicrobial Resistance in France: A Matched Case-Control Study.

Appl Health Econ Health Policy 2019 06;17(3):381-389

Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, Paris-Saclay University, 2, avenue de la Source de la Bièvre, 78180, Montigny-Le-Bretonneux, France.

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.
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http://dx.doi.org/10.1007/s40258-018-0451-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535148PMC
June 2019

Pleural effusion during weaning from mechanical ventilation: a prospective observational multicenter study.

Ann Intensive Care 2018 Nov 1;8(1):103. Epub 2018 Nov 1.

AP-HP, DHU A-TVB, Service de Réanimation Médicale, Hôpitaux Universitaires Henri Mondor, 94010, Créteil, France.

Background: Pleural effusion is common during invasive mechanical ventilation, but its role during weaning is unclear. We aimed at assessing the prevalence and risk factors for pleural effusion at initiation of weaning. We also assessed its impact on weaning outcomes and its evolution in patients with difficult weaning.

Methods: We performed a prospective multicenter study in five intensive care units in France. Two hundred and forty-nine patients were explored using ultrasonography. Presence of moderate-to-large pleural effusion (defined as a maximal interpleural distance ≥ 15 mm) was assessed at weaning start and during difficult weaning.

Results: Seventy-three (29%) patients failed weaning, including 46 (18%) who failed the first spontaneous breathing trial (SBT) and 39 (16%) who failed extubation. Moderate-to-large pleural effusion was detected in 81 (33%) patients at weaning start. Moderate-to-large pleural effusion was associated with more failures of the first SBT [27 (33%) vs. 19 (11%), p < 0.001], more weaning failures [37 (47%) vs. 36 (22%), p < 0.001], less ventilator-free days at day 28 [21 (5-24) vs. 23 (16-26), p = 0.01], and a higher mortality at day 28 [14 (17%) vs. 14 (8%), p = 0.04]. The association of pleural effusion with weaning failure persisted in multivariable analysis and sensitivity analyses. Short-term (48 h) fluid balance change was not associated with the evolution of interpleural distance in patients with difficult weaning.

Conclusions: In this multicenter observational study, pleural effusion was frequent during the weaning process and was associated with worse weaning outcomes.
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http://dx.doi.org/10.1186/s13613-018-0446-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211142PMC
November 2018

Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial.

JAMA 2018 11;320(20):2087-2098

Medical Microbiology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.

Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown.

Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance.

Design, Setting, And Participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum β-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017.

Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily.

Main Outcomes And Measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period.

Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline.

Conclusions And Relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care.

Trial Registration: ClinicalTrials.gov Identifier: NCT02208154.
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http://dx.doi.org/10.1001/jama.2018.13765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583563PMC
November 2018

Long-term Quality of Life in Adult Patients Surviving Purpura Fulminans: An Exposed-Unexposed Multicenter Cohort Study.

Clin Infect Dis 2019 07;69(2):332-340

Service de Réanimation Médicale, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil.

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.
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http://dx.doi.org/10.1093/cid/ciy901DOI Listing
July 2019

Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study.

Intensive Care Med 2018 Sep 20;44(9):1502-1511. Epub 2018 Aug 20.

Service de Réanimation Médicale, Groupe de Recherche CARMAS, Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire Henri Mondor, 51, Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil, France.

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.
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http://dx.doi.org/10.1007/s00134-018-5341-3DOI Listing
September 2018

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

N Engl J Med 2018 Mar;378(9):809-818

From Service de Médecine Intensive et Réanimation, Hôpital Raymond Poincaré, Garches (D.A., V.M.), Laboratory of Infection and Inflammation Unité 1173, University of Versailles Saint-Quentin-en-Yvelines, INSERM, Montigny-le-Bretonneux (D.A.), Service de Pharmacologie Clinique-Centre d'Investigation Clinique (CIC) INSERM 1414, Centre Hospitalier Universitaire (CHU) de Rennes-Université de Rennes 1, Hôpital Pontchaillou, Rennes (A.R., E.B.), Service de Réanimation Médicale (C.B.-B.) and Service d'Anesthésie et des Réanimations Chirurgicales (G.D., F.C.), Hôpital Henri-Mondor (Assistance Publique-Hôpitaux de Paris [AP-HP]), Créteil, Réanimation Médicale et Toxicologique, Hôpital Lariboisière (AP-HP), Université Paris-Diderot, INSERM Unité Mixte de Recherche Scientifique (UMRS) 1144 (B. Megarbane), Réanimation Médicale-Hôpitaux Universitaires Paris Centre-Site Cochin (AP-HP) and Université Paris Descartes (A. Cariou), Médecine Intensive et Réanimation, Pôle 2i, Infection et Immunité, Hôpital Bichat-Claude Bernard, AP-HP, Infection, Antimicrobiens, Modélisation, Evolution (IAME) Unité 1137, Université Paris Diderot, INSERM (J.-F.T.), Service d'Anesthésie et Réanimations Chirurgicales, Hôpitaux Universitaires Paris Centre-Site Cochin (AP-HP) (F.B.), and Service de Réanimation Médicale, Hôpital Pitié-Salpêtrière (AP-HP), and Université Paris Sorbonne INSERM, UMRS 1166-Institute of Cardiometabolism and Nutrition (A. Combes), Paris, Service de Réanimation Médicale, Hôpital Universitaire François Mitterrand, Lipness Team, INSERM Research Center Lipids, Nutrition, Cancer-Unité Mixte de Recherche (UMR) 1231 and Laboratoire d'Excellence LipSTIC, and CIC 1432, Epidémiologie Clinique, Université de Burgundy, Dijon (J.-P.Q., A.D.), Service d'Anesthésie-Réanimation, Centre Hospitalier d'Etampes, Etampes (S.S., T.H.), Réanimation Médico-Chirurgicale, CIC INSERM 1414, Grand Hôpital de l'Est Francilien Site de Meaux, Hôpital Saint Faron, Meaux (X.F.), Service de Réanimation Médicale, CHU de Grenoble, Grenoble (C.S.), Service d'Anesthésie et de Réanimation, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Aix Marseille Université, CIC 1409, and CIC 9502, Marseille (C.M.), Service de Réanimation Polyvalente, Groupe Hospitalier Paris Saint Joseph, and Service de Réanimation Médicale, CHU de Rouen-Hôpital Charles Nicolle, Rouen (B. Misset), Service de Réanimation Polyvalente, Centre Hospitalier de Valenciennes, Valenciennes (M.A.B.), Service de Réanimation Médico-Chirurgicale, Centre Hospitalier Départemental de Vendée, Site de La Roche-sur-Yon, Les Oudairies, La Roche-sur-Yon (G. Colin), Réanimation Médicale Polyvalente, CHU Gabriel Montpied (B.S.), and Pôle de Médecine Péri-Opératoire, Génétique, Reproduction, et Développement, UMR-Centre National de la Recherche Scientifique 6293, Université Clermont-Auvergne, INSERM Unité 1103, CHU Clermont-Ferrand (J.-M.C.), Clermont-Ferrand, Service d'Anesthésie, Réanimation Chirurgicale, Hôtel Dieu-Hôpital Mère-Enfant, CHU Nantes, Laboratoire EA3826 Thérapeutiques et Expérimentales des Infections, Nantes (K.A.), Réanimation Polyvalente, Centre Hospitalier Régional Universitaire Bretonneau, Tours (E.M.), Service d'Anesthésie-Réanimation, Centre Hospitalier de Périgueux, Périgueux (L.C.), Service de Réanimation Chirurgicale, Hôpital Central, CHU de Nancy, Nancy (C.C.), Service de Réanimation Polyvalente, INSERM CIC 1435-CHU Dupuytren, Limoges (B.F.), Service Réanimation Médicale Polyvalente et Unité de Surveillance Continue, Centre Hospitalier Régional d'Orléans, Orléans (T.B.), Réanimation Chirurgicale, Département d'Anesthésie-Réanimations-Urgences, Service d'Assistance Médicale d'Urgence (SAMU) 86, Hôpital de la Miletrie, CHU, Poitiers (F.P.), Service de Réanimation Médicale, Centre Hospitalier Lyon-Sud (Hospices Civils de Lyon), Pierre-Bénite (J.B.), Service d'Anesthésie-Réanimation, Hôpital Saint Camille, Bry-sur-Marne (J.-F.L.), Réanimation Polyvalente, Hôpital Jean Verdier (AP-HP), Bondy (R.A.), Service de Réanimation Médicale, CHU Amiens-Picardie-Site Sud, Amiens (M.S.), Service de Réanimation Médicale et Maladies Infectieuses, Centre Hospitalier Tourcoing Gustave Dron, Tourcoing (O.L.), and Service de Réanimation Médicale-SAMU 25, Hôpital Jean Minjoz-CHU de Besançon, Besançon (G. Capellier) - all in France.

Background: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.

Methods: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group).

Results: Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure-free days (14 vs. 12 days, P=0.003). The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group.

Conclusions: In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. (Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health; APROCCHSS ClinicalTrials.gov number, NCT00625209 .).
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http://dx.doi.org/10.1056/NEJMoa1705716DOI Listing
March 2018

Comparing antibiotic consumption between two European countries: are packages an adequate surrogate for prescriptions?

Euro Surveill 2017 Nov;22(46)

Ministère de la Santé, Paris, France.

Defined daily doses (DDD) are the gold standard indicator for quantifying prescriptions. Since 2014, the European Centre for Disease Prevention and Control (ECDC) has also been using the number of packages per 1,000 inhabitants per day (ipd), as a surrogate for prescriptions, to report antibiotic consumption in the community and to perform comparisons between European Union (EU) countries participating in the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). In 2015, consumption was reported to range across Europe from 1.0 to 4.7 packages per 1,000 ipd. Our analysis showed that consumption of antibiotics for systemic use per 1,000 ipd was on average 1.3 times greater in France than in Belgium when considering prescriptions in the numerator, 2.5 times greater when considering packages and 1.2 times greater when considering DDD. As long as the same metrics are used over time, antibiotic consumption data aggregated and disseminated by ECDC are useful for assessing temporal trends at the European level and within individual countries; these data may also be used for benchmarking across EU countries. While DDD - although imperfect - are the most widely accepted metric for this purpose, antibiotic packages do not appear suitable for comparisons between countries and may be misleading.
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http://dx.doi.org/10.2807/1560-7917.ES.2017.22.46.17-00352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718399PMC
November 2017

Piperacillin-tazobactam as alternative to carbapenems for ICU patients.

Ann Intensive Care 2017 Nov 10;7(1):113. Epub 2017 Nov 10.

Réanimation médicale, Hôpital Henri Mondor, Université Paris Est Créteil (UPEC), Créteil, France.

Several studies suggest that alternatives to carbapenems, and particulary beta-lactam/beta-lactamase inhibitor combinations, can be used for therapy of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE)-related infections in non-ICU patients. Little is known concerning ICU patients in whom achieving the desired plasmatic pharmacokinetic/pharmacodynamic (PK/PD) target may be difficult. Also, in vitro susceptibility to beta-lactamase inhibitors might not translate into clinical efficacy. We reviewed the recent clinical studies examining the use of BL/BLI as alternatives to carbapenems for therapy of bloodstream infection, PK/PD data and discuss potential ecological benefit from avoiding the use of carbapenems. With the lack of prospective randomized studies, treating ICU patients with ESBL-PE-related infections using piperacillin-tazobactam should be done with caution. Current data suggest that BL/BLI empirical use should be avoided for therapy of ESBL-PE-related infection. Also, definitive therapy should be reserved to patients in clinical stable condition, after microbial documentation and results of susceptibility tests. Optimization of administration and higher dosage should be used in order to reach pharmacological targets.
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http://dx.doi.org/10.1186/s13613-017-0334-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681454PMC
November 2017

Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.

Shock 2018 06;49(6):641-648

Service de Réanimation Médicale, Hôpitaux Universitaires Henri Mondor, Hôpitaux de Paris, DHU A-TVB, Créteil, France.

Background: Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators.

Methods: Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded.

Results: Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia.

Conclusion: Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.
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http://dx.doi.org/10.1097/SHK.0000000000001015DOI Listing
June 2018

Association between relative adrenal insufficiency and septic cardiomyopathy: a preliminary report.

Intensive Care Med 2017 12 4;43(12):1924-1926. Epub 2017 Aug 4.

Service de Réanimation Médicale, AP-HP, Centre Hospitalo-Universitaire Henri Mondor, DHU A-TVB, 51, Avenue du Mal de Lattre de Tassigny, 94010, Créteil Cedex, France.

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http://dx.doi.org/10.1007/s00134-017-4901-2DOI Listing
December 2017

Etiologies, diagnostic work-up and outcomes of acute respiratory distress syndrome with no common risk factor: a prospective multicenter study.

Ann Intensive Care 2017 Dec 19;7(1):69. Epub 2017 Jun 19.

Service de Réanimation Médicale, DHU A-TVB, Hôpitaux Universitaires Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil Cedex, 94010, France.

Background: Patients meeting the Berlin definition for the acute respiratory distress syndrome (ARDS) might lack exposure to one or more "common" risk factors and exhibit different clinical phenotype and outcomes. We aimed to compare the clinical presentation and outcome of ARDS patients with or without risk factors, the impact on hospital mortality, and to assess the diagnostic work-up performed. The current study is an ancillary analysis of an international, multicenter, prospective cohort study (the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure, LUNG SAFE). Patients meeting ARDS criteria within 2 days of acute hypoxemic respiratory failure onset were included in the study and categorized as having risk factors or not. Outcomes were compared using propensity score matching.

Results: Among 2813 patients, 234 (8.3% [7.3-9.3]) had no ARDS risk factor identified. These were older, had more frequent chronic diseases and presented with less severe SOFA and non-pulmonary SOFA scores (p < 0.001). Compared to other ARDS, CT scan (32.1 vs 23.9%, p < 0.001) and open lung biopsy (2.6 vs 0.2%, p < 0.001) were slightly more frequent but left heart filling pressures assessment was not (69.4 vs 68.4%, p > 0.99). Among ARDS with no risk factor, 45 patients (19.2%) had a specific diagnosis made. As compared to others, patients having ARDS with no risk factor had a lower ICU but not hospital mortality (34.6 vs 40.0%; p = 0.12). A matched cohort analysis confirmed the lack of significant difference in mortality.

Conclusion: Eight percent of ARDS patients have no identified risk factor, 80% of whom have no etiological diagnosis made. The outcome of ARDS with no risk factor was comparable to other ARDS but few had a comprehensive diagnostic work-up, potentially leading to missed curable diseases. Trial registration clinicaltrials.gov Identifier: NCT02010073.
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http://dx.doi.org/10.1186/s13613-017-0281-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476531PMC
December 2017

Frequency, associated factors and outcome of multi-drug-resistant intensive care unit-acquired pneumonia among patients colonized with extended-spectrum β-lactamase-producing Enterobacteriaceae.

Ann Intensive Care 2017 Dec 12;7(1):61. Epub 2017 Jun 12.

Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, 94010, Créteil, France.

Background: We assessed prevalence, associated factors and prognosis of extended-spectrum beta-lactamase-producing Enterobacteriaceae pneumonia acquired in intensive care unit (ESBL-PE pneumonia) among carriers. Variables associated with nosocomial pneumonia caused by carbapenem-resistant bacteria (CRB) were also assessed.

Methods: A 6-year prospective study (May 2009-March 2015) in the medical ICU of an 850-bed university-affiliated hospital was conducted.

Results: Of the 6303 patients admitted, 843 (13.4%) had ESBL-PE carriage detected. Among carriers, 111 (13%) patients developed ICU-acquired pneumonia of whom 48 (43%) had ESBL-PE pneumonia (6% of carriers). By multivariable analysis, SAPS II at admission >43 [OR 2.81 (1.16-6.79)] and colonization with Enterobacter sp. or K. pneumoniae species [OR 10.96 (2.93-41.0)] were independent predictive factors for ESBL-PE pneumonia in colonized patients, whereas receipt of >2 days of amoxicillin/clavulanic acid during the ICU stay [OR 0.24 (0.08-0.71)] was protective. Patients with ESBL-PE pneumonia had a higher SOFA score (p = 0.037) and more frequent septic shock at pneumonia onset (p = 0.047). However, ESBL-PE pneumonia was not an independent predictor of mortality. Twenty-five patients had pneumonia caused by CRB. Chronic renal insufficiency, administration of third-generation cephalosporin within the past 3 months, acute respiratory distress syndrome before pneumonia and prior therapy with a carbapenem or fluoroquinolones were associated with CRB pneumonia in this selected population.

Conclusions: Although few ESBL-PE carriers developed ESBL-PE pneumonia overall, a high proportion of pneumonia were caused by ESBL-PE in carriers developing ICUAP. ESBL-PE pneumonia was not an independent predictor of mortality. As pneumonia caused by CRB is increasing, knowledge of factors associated with ESBL-PE or CRB pneumonia may help empiric therapy of pneumonia among ESBL-PE carriers.
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http://dx.doi.org/10.1186/s13613-017-0283-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468364PMC
December 2017

Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial.

Intensive Care Med 2017 Nov 3;43(11):1613-1625. Epub 2017 Apr 3.

APHP-Henri Mondor, Public Health Department, 94010, Créteil, France.

Purpose: Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE).

Methods: Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCyclerSeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE).

Results: A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P < 0.001], with an absolute increase of 14.5% (95% CI 8.4-20.7). A trend towards an association was observed for SIE [35.4% (17/48) vs. 9.5% (2/21); OR 6.22 (0.98-39.6)], but not for FN [32.1% (70/218) vs. 30.2% (67/222), P = 0.66]. Overall, turn-around time was shorter during IP than during CP (22.9 vs. 49.5 h, P < 0.001) and hospital costs were similar (median, mean ± SD: IP €14,826, €18,118 ± 17,775; CP €17,828, €18,653 ± 15,966). Bootstrap analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients.

Conclusion: Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.
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http://dx.doi.org/10.1007/s00134-017-4766-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633620PMC
November 2017

Erratum to 'Predominance of healthcare-associated cases among episodes of community-onset bacteraemia due to extended-spectrum β-lactamase-producing Enterobacteriaceae' [International Journal of Antimicrobial Agents 49/1 67-73].

Int J Antimicrob Agents 2017 04 6;49(4):480-481. Epub 2017 Mar 6.

Medical Intensive Care Unit and Infection Control Unit, Henri Mondor University Hospital, APHP, Paris-Est Créteil University (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijantimicag.2017.02.007DOI Listing
April 2017

Left ventricular systolic dysfunction during septic shock: the role of loading conditions.

Intensive Care Med 2017 May 15;43(5):633-642. Epub 2017 Feb 15.

AP-HP, Hôpitaux universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, 94010, Créteil, France.

Purpose: The clinical significance of septic myocardial dysfunction is controversial, a fact that may be explained by the influence of loading conditions. Many indices may be useful to characterize cardiac function during septic shock, but their feasibility and physiological coherence in the clinical setting are unknown.

Methods: Hemodynamic and echocardiographic data with tissue Doppler and speckle tracking were prospectively recorded on the first 3 days of human septic shock. Hypokinesia, normokinesia, and hyperkinesia were defined as a left ventricular ejection fraction (LVEF) of <45, 45-60, and >60%, respectively. Twelve hemodynamic indices exploring contractility and loading conditions were assessed and analyzed.

Results: Two hundred and ninety-seven echocardiographies were performed in 132 patients. During the first 24 h (H), 48 (36.4%) patients were hyperkinetic, 55 (41.7%) were normokinetic, and 29 (22.0%) patients were hypokinetic. Thirteen patients had a secondary hypokinesia absent at H but present at H or H, for an overall incidence of 42 (31.8%) during the first 3 days. Despite a limited feasibility (<50%), global LV longitudinal peak systolic strain was impaired in a majority (>70%) of the patients assessed, including all those with depressed LVEF, and declined early in patients whose LVEF secondarily deteriorated. Most contractility indices were inversely correlated with afterload indices. Hyperkinetic patients exhibited the worst reduction in afterload indices. Hospital mortality was significantly higher in patients with LV hyperkinesia than in their counterparts: 30 (62.5%) vs. 35 (41.7%), p = 0.02.

Conclusions: Speckle tracking-derived strain was reduced in the majority of patients with septic shock, revealing covert septic myocardial dysfunction, but had poor feasibility. We found an inverse correlation between most of the contractility and afterload indices. Precise evaluation of afterload is crucial for adequate interpretation of LV systolic function in this setting.
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http://dx.doi.org/10.1007/s00134-017-4698-zDOI Listing
May 2017

Antimicrobial strategy for severe community-acquired legionnaires' disease: a multicentre retrospective observational study.

J Antimicrob Chemother 2017 05;72(5):1502-1509

AP-HP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Service de Réanimation Médicale, Créteil, France.

Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases.

Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality.

Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used.

Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P  =   0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P  =   0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P  =   0.02].

Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates.
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http://dx.doi.org/10.1093/jac/dkx007DOI Listing
May 2017

[Prudent antibiotic use in response to the antimicrobial resistance challenges].

Rev Prat 2017 02;67(2):217-222

Université Paris-Est-Créteil, groupe hospitalier Henri-Mondor, Créteil, France.

Prudent antibiotic use in response to the antimicrobial resistance challenges. Appropriate antimicrobial use and hospital infection control are the two pillars on which control of antimicrobial resistance relies. Components of prudent antimicrobial prescribing in the hospital setting include : 1) an accurate microbiological diagnosis of the infection treated using appropriate microbiological samplings before initiating therapy, while avoiding treatment of patients only colonised ; 2) reappraisal of therapy at 48 to 72 h, considering de-escalation and considering PK/PD parameters; 3) reappraisal of therapy in between the 5th and 7th day, giving consideration to shortening the duration of therapy to the minimum effective length. Local epidemiology is also important to consider, especially in high-risk units. Antimicrobial stewardship teams have an important role to play in the overall fight against antimicrobial resistance in hospitals, notably regarding good prescribing of "critically important" antibiotics.
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February 2017

Clostridium difficile contamination of health care workers' hands and its potential contribution to the spread of infection: Review of the literature.

Am J Infect Control 2017 01;45(1):51-58

National Reference Laboratory for Clostridium difficile, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Groupe de recherche clinique EPIDIFF, Université Pierre et Marie Curie, Paris, France.

Background: Clostridium difficile infection (CDI) can be transmitted from patient to patient by the hands of health care workers (HCWs); however, the relative importance of this route in the spread of C difficile in the hospital is currently unknown. Our aim was to review studies examining HCWs' hand carriage and its potential role in CDI transmission.

Methods: First, English-speaking references addressing HCWs' hand sampling obtained from the PubMed database were reviewed. Second, C difficile outbreaks definitely or probably implicating HCWs were retrieved from the Outbreak Database Web site (www.outbreak-database.com). Finally, cases of C difficile occurring in HCWs after contact with an infected patient were retrieved from PubMed.

Results: A total of 11 studies dealing with HCWs' hand carriage were selected and reviewed. Between 0% and 59% of HCWs' hands were found contaminated with C difficile after caring for a patient with CDI. There were several differences between studies regarding site of hands sampling, timing after contact, and bacteriologic methods. Only 2 C difficile outbreaks implicating HCWs and 6 series of cases of transmission from patients to HCWs have been reported.

Conclusions: This review shows that HCWs' hands could play an important role in the transmission of C difficile. Hand hygiene and reduction of environmental contamination are essential to control C difficile transmission.
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http://dx.doi.org/10.1016/j.ajic.2016.08.017DOI Listing
January 2017

Prognostic Value of Relative Adrenal Insufficiency During Cardiogenic Shock: A Prospective Cohort Study With Long-Term Follow-Up.

Shock 2017 01;47(1):86-92

*AP-HP, CHU Henri Mondor, DHU A-TVB, Department of Medical Intensive Care, Créteil, France †Université Paris Est Créteil, Faculté de Médecine, Groupe de recherche clinique CARMAS, Créteil, France ‡AP-HP, CHU Henri Mondor, DHU A-TVB, Department of Cardiology, Créteil, France §AP-HP, CHU Henri Mondor, Department of Biochemistry, Créteil, France.

Background: Relative adrenal insufficiency (RAI) is common in intensive care unit patients, particularly during septic shock (SS). Cardiogenic shock (CS) may share some pathophysiological features with SS. The aim of this study was to evaluate the prevalence and long-term prognosis of RAI during CS.

Patients And Methods: Prospective observational study conducted in the intensive care and cardiology units in one university hospital in France. Patients meeting the criteria for CS without prior corticosteroid therapy were included. Total blood cortisol levels were assessed immediately before (T0) a short corticotropin stimulation test (0.25 mg i.v. of tetracosactrin) and 30 and 60 min afterward. Δmax was defined as the difference between the maximal value after the test and T0.

Results: Of the 92 patients enrolled, 42 (46%) (95% confidence interval [CI] [36%-56%]) died in hospital and 7 more died during a median follow-up of 616 [57-2,498] days, for an overall mortality rate of 53% (95% CI [43%-63%]). Three groups were identified based on the corticotropin test: group 1 (T0 ≤798 nmol/L and Δmax >473 nmol/L), group 2 ([T0 >798 nmol/L and Δmax >473 nmol/L] or [T0 ≤798 nmol/L and Δmax ≤473 nmol/L]), and group 3 (T0 >798 nmol/L and Δmax ≤473 nmol/L) with an overall survival of 76%, 43%, and 15%, respectively (log rank P = 0.003). In the multivariable analysis, adrenal nonresponse (group 3) was an independent predictor of mortality (P = 0.04), along with left ventricular ejection fraction, Simplified Acute Physiology Score II, and cardiac arrest.

Conclusions: These data suggest that a short corticotropin test has a good prognostic value in CS and allows identifying patients at higher risk of death.
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http://dx.doi.org/10.1097/SHK.0000000000000710DOI Listing
January 2017

Predominance of healthcare-associated cases among episodes of community-onset bacteraemia due to extended-spectrum β-lactamase-producing Enterobacteriaceae.

Int J Antimicrob Agents 2017 Jan 16;49(1):67-73. Epub 2016 Nov 16.

Medical Intensive Care Unit and Infection Control Unit, Henri Mondor University Hospital, APHP, Paris-Est Créteil University (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France. Electronic address:

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are endemic pathogens worldwide. Infection with ESBL-PE may be associated with inadequate antibiotic therapy and a poor outcome. However, risk factors for ESBL-PE community-acquired infections are ill-defined. An observational multicentre study was performed in 50 hospitals to identify the prevalence of and risk factors for community-acquired ESBL-PE bacteraemia. All patients presenting with community-onset Enterobacteriaceae bacteraemia were recorded over a 2-month period (between June and November 2013). Risk factors and 14-day outcomes of patients were investigated. Among 682 Enterobacteriaceae bacteraemia episodes recorded, 58 (8.5%) were caused by ESBL-PE. The most frequent species isolated were Escherichia coli (537; 76.7%) and Klebsiella spp. (68; 9.7%), of which 49 (9.1%) and 8 (11.8%), respectively, were ESBL-producers. Most ESBL-PE episodes were healthcare-associated, and only 22 (38%) were apparently community-acquired. The main risk factor for community-acquired ESBL-PE bacteraemia was a prior hospital stay of ≥5 days within the past year. The overall 14-day survival was 90%; only 4 (6.9%) of 58 patients with ESBL-PE bacteraemia died. Inadequate initial antibiotic therapy was administered to 55% of patients with ESBL-PE bacteraemia but was not associated with increased 14-day mortality. Although many patients had community-onset ESBL-PE bacteraemia, almost two-thirds of the episodes were actually healthcare-associated, and true community-acquired ESBL-PE bacteraemia remains rare. In our essentially non-severely ill population, inappropriate initial therapy was not associated with a higher risk of mortality.
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http://dx.doi.org/10.1016/j.ijantimicag.2016.09.032DOI Listing
January 2017

Septic shock with no diagnosis at 24 hours: a pragmatic multicenter prospective cohort study.

Crit Care 2016 Nov 6;20(1):360. Epub 2016 Nov 6.

Service de réanimation Médicale, Groupe de Recherche CARMAS, Centre Hospitalier Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, 51, avenue du Maréchal de Lattre de Tassigny, Créteil, 94010, France.

Background: The lack of a patent source of infection after 24 hours of management of shock considered septic is a common and disturbing scenario. We aimed to determine the prevalence and the causes of shock with no diagnosis 24 hours after its onset, and to compare the outcomes of patients with early-confirmed septic shock to those of others.

Methods: We conducted a pragmatic, prospective, multicenter observational cohort study in ten intensive care units (ICU) in France. We included all consecutive patients admitted to the ICU with suspected septic shock defined by clinical suspicion of infection leading to antibiotic prescription plus acute circulatory failure requiring vasopressor support.

Results: A total of 508 patients were admitted with suspected septic shock. Among them, 374 (74 %) had early-confirmed septic shock, while the 134 others (26 %) had no source of infection identified nor microbiological documentation retrieved 24 hours after shock onset. Among these, 37/134 (28 %) had late-confirmed septic shock diagnosed after 24 hours, 59/134 (44 %) had a condition mimicking septic (septic shock mimicker, mainly related to adverse drug reactions, acute mesenteric ischemia and malignancies) and 38/134 (28 %) had shock of unknown origin by the end of the ICU stay. There were no differences between patients with early-confirmed septic shock and the remainder in ICU mortality and the median duration of ICU stay, of tracheal intubation and of vasopressor support. The multivariable Cox model showed that the risk of day-60 mortality did not differ between patients with or without early-confirmed septic shock. A sensitivity analysis was performed in the subgroup (n = 369/508) of patients meeting the Sepsis-3 definition criteria and displayed consistent results.

Conclusions: One quarter of the patients admitted in the ICU with suspected septic shock had no infection identified 24 hours after its onset and almost half of them were eventually diagnosed with a septic shock mimicker. Outcome did not differ between patients with early-confirmed septic shock and other patients.
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http://dx.doi.org/10.1186/s13054-016-1537-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097846PMC
November 2016

A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med 2017 04;195(7):871-880

9 Institut national de la santé et de la recherche médicale, UMR 955, Université Paris Est, Créteil, France.

Rationale: During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O, but its impact on clinical outcomes remains unknown.

Objectives: To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations.

Methods: This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with Pa ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, Pa ≤ 50 mm Hg, and oxygen saturation (arterial [Sa] or measured by pulse oximetry [Sp]) ≤ 90%. A 6-month follow-up was performed.

Measurements And Main Results: The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, Pa, and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality.

Conclusions: Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).
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http://dx.doi.org/10.1164/rccm.201601-0083OCDOI Listing
April 2017

A diagnostic nomogram for delayed hemolytic transfusion reaction in sickle cell disease.

Am J Hematol 2016 12 7;91(12):1181-1184. Epub 2016 Sep 7.

Laboratory of Excellence GRex, INSERM U955, Equipe 2, Créteil, France.

Diagnosis of delayed hemolytic transfusion reactions (DHTR), one of the most dreaded complications of transfusion in patients with sickle cell disease (SCD), is challenging and not straightforward. Current diagnostic approaches are complex and not consensual; they are based on assessment of hemoglobin (Hb) drop and enhanced hemolysis, features also seen during classical vaso-occlusive events. In this observational study, we tested the hypothesis that the rate of decline in HbA after an index transfusion is a surrogate marker for the destruction of transfused RBC, which could be used diagnostically. We examined 421 transfusion episodes (in 128 patients of a French referral center for SCD) for which an Hb electrophoresis was obtained within 1 week following an index transfusion and repeated within 2 months (before a subsequent scheduled transfusion or during an acute complication). Chart review found DHTR to be present in 26 cases (6.2%), absent in 389 cases (92.4%), and possible in six cases (1.4%). As expected, DHTR was associated with accelerated hemolysis (increased serum bilirubin and lactic dehydrogenase concentrations) and a decline in total Hb as compared to the early post-transfusion value. However, the decline in HbA concentration appeared more effective in segregating between patients without DHTR and others. We propose a diagnostic nomogram for DHTR based on Hb A as a biologic marker of the survival of transfused RBCs. Am. J. Hematol. 91:1181-1184, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajh.24537DOI Listing
December 2016

Aspergillus-positive lower respiratory tract samples in patients with the acute respiratory distress syndrome: a 10-year retrospective study.

Ann Intensive Care 2016 Dec 13;6(1):52. Epub 2016 Jun 13.

Groupe Henri Mondor-Albert Chenevier, Centre Hospitalier Universitaire Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, Assistance Publique-Hôpitaux de Paris, 51, Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.

Background: The detection of Aspergillus spp. in endotracheal aspirate cultures of mechanically ventilated patients may reflect either colonization or infection. However, little is known about the prevalence and the impact on outcome of respiratory tract sample positive for Aspergillus during the acute respiratory distress syndrome (ARDS).

Methods: We conducted a monocentric, retrospective study over a 10-year period (January 2006-December 2015) in the ICU of a university hospital. All consecutive adult patients with ARDS were included, and the diagnosis of invasive pulmonary aspergillosis was assessed using a previously validated algorithm.

Results: In total, 423 ARDS patients were included with 35 patients [8.3 %, 95 % CI (5.4-10.6)] having at least one respiratory tract sample positive for Aspergillus (Aspergillus(+) patients) after a median delay of 3 days (1-11) following ICU admission. Comorbidities did not differ between Aspergillus(+) and Aspergillus(-) patients except for more frequent immunosuppression in Aspergillus(+) patients (40 vs. 22 %; p = 0.02). There was no difference between Aspergillus(-) and Aspergillus(+) patients regarding in-ICU mortality, ventilator-free days at day 28, and incidence of ventilator-associated pneumonia, but need for renal replacement therapy was higher in Aspergillus(+) patients than in others (49 vs. 27 %; p = 0.01). Seventeen [4.0 %, 95 % CI (2.1-5.9)] patients had putative/proven aspergillosis. After adjusting on covariates associated with ICU mortality, putative/proven aspergillosis was associated with in-ICU mortality [aOR = 9.58 (1.97-46.52); p = 0.005], while Aspergillus colonization was not [aOR = 0.64 (0.21-1.99); p = 0.44].

Conclusions: Eight percent of ARDS patients had Aspergillus spp.-positive respiratory tract cultures. These had a higher risk of mortality only when categorized as having putative or proven invasive pulmonary aspergillosis.
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http://dx.doi.org/10.1186/s13613-016-0156-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906097PMC
December 2016