Bruno Mégarbane

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (271)878.41 Total impact

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    ABSTRACT: Critically ill patients who require renal replacement therapy (RRT) are vulnerable to catheter-related bloodstream infections (CRBSI). This study compared the risk of dialysis catheter infection according to the locking solution in the intensive care unit (ICU).
    Antimicrobial Agents and Chemotherapy 06/2014; · 4.57 Impact Factor
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    ABSTRACT: Prediction of arterial thromboembolic events (ATEs) in relation to supraventricular arrhythmia (SVA) has been poorly investigated in the intensive care unit (ICU). We aimed at evaluating CHADS2 and CHA2DS2-VASc scores to predict SVA-related ATE in the ICU.
    Journal of critical care. 05/2014;
  • B Mégarbane, D Résière
    Annales francaises d'anesthesie et de reanimation 05/2014; · 0.77 Impact Factor
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    ABSTRACT: Fomepizole, a potent alcohol dehydrogenase inhibitor was shown to be an effective and safe antidote for treating toxic alcohol poisoning in adults [1]. However, evidence for its effectiveness and safety in children remains limited [2]. We reviewed the records of children treated with fomepizole sulfate (Fomepizole AP-HP®), the only marketed product in France, manufactured and distributed by the state pharmaceutical agency for Paris hospitals (AGEPS).This article is protected by copyright. All rights reserved.
    Basic & Clinical Pharmacology & Toxicology 05/2014; · 2.18 Impact Factor
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    ABSTRACT: We investigated the predictive factors for extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE) causing infections among intensive care unit patients with prior documented ESBL-PE colonization. Using multivariate analysis, referral from medical ward, nursing home or rehabilitation center [Odds ratio (OR), 2.5; 95 % confidence interval (CI), [1.3-5.0]; p = 0.007], previous fluoroquinolone treatment (OR, 3.4; CI, [1.1-10.5]; p = 0.003), extracorporeal membrane oxygenation (OR, 4.6; CI, [1.3-15.9]; p = 0.02), and absence of prior positive ESBL-PE rectal swab culture (OR, 5.0; CI, [1.6-10.0]; p = 0.0009) were risk factors for ESBL-PE infection. Easily identifiable factors may help with targeting carbapenem prescriptions.
    Infection 04/2014; · 2.44 Impact Factor
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    ABSTRACT: In patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest, two blood gas management strategies are used regarding the PaCO2 target: α-stat or pH-stat. We aimed to compare the effects of these strategies on cerebral blood flow and oxygenation. Prospective observational single-center crossover study. ICU of University hospital. Twenty-one therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest more than 18 years old without history of cerebrovascular disease were included. Cerebral perfusion and oxygenation variables were compared in α-stat (PaCO2 measured at 37°C) versus pH-stat (PaCO2 measured at 32-34°C), both strategies maintaining physiological PaCO2 values: 4.8-5.6 kPa (36-42 torr). Bilateral transcranial middle cerebral artery flow velocities using Doppler and jugular vein oxygen saturation were measured in both strategies 18 hours (14-23 hr) after the return of spontaneous circulation. Pulsatility and resistance indexes and cerebral oxygen extraction were calculated. Data are expressed as median (interquartile range 25-75) in α-stat versus pH-stat. No differences were found in temperature, arterial blood pressure, and oxygenation between α-stat and pH-stat. Significant differences were found in minute ventilation (p = 0.006), temperature-corrected PaCO2 (4.4 kPa [4.1-4.6 kPa] vs 5.1 kPa [5.0-5.3 kPa], p = 0.0001), and temperature-uncorrected PaCO2 (p = 0.0001). No differences were found in cerebral blood velocities and pulsatility and resistance indexes in the overall population. Significant differences were found in jugular vein oxygen saturation (83.2% [79.2-87.6%] vs 86.7% [83.2-88.2%], p = 0.009) and cerebral oxygen extraction (15% [11-20%] vs 12% [10-16%], p = 0.01), respectively. In survivors, diastolic blood velocities were 25 cm/s (19-30 cm/s) versus 29 cm/s (23-35 cm/s) (p = 0.004), pulsatility index was 1.10 (0.97-1.18) versus 0.94 (0.89-1.05) (p = 0.027), jugular vein oxygen saturation was 79.2 (71.1-81.8) versus 83.3% (76.6-87.8) (p = 0.033), respectively. However, similar results were not found in nonsurvivors. In therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest at physiological PaCO2, α-stat strategy increases jugular vein blood desaturation and cerebral oxygen extraction compared with pH-stat strategy and decreases cerebral blood flow velocities in survivors.
    Critical care medicine 04/2014; · 6.37 Impact Factor
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    ABSTRACT: Background The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown. Methods In a multicenter, open-label trial, we randomly assigned 776 patients with septic shock to undergo resuscitation with a mean arterial pressure target of either 80 to 85 mm Hg (high-target group) or 65 to 70 mm Hg (low-target group). The primary end point was mortality at day 28. Results At 28 days, there was no significant between-group difference in mortality, with deaths reported in 142 of 388 patients in the high-target group (36.6%) and 132 of 388 patients in the low-target group (34.0%) (hazard ratio in the high-target group, 1.07; 95% confidence interval [CI], 0.84 to 1.38; P=0.57). There was also no significant difference in mortality at 90 days, with 170 deaths (43.8%) and 164 deaths (42.3%), respectively (hazard ratio, 1.04; 95% CI, 0.83 to 1.30; P=0.74). The occurrence of serious adverse events did not differ significantly between the two groups (74 events [19.1%] and 69 events [17.8%], respectively; P=0.64). However, the incidence of newly diagnosed atrial fibrillation was higher in the high-target group than in the low-target group. Among patients with chronic hypertension, those in the high-target group required less renal-replacement therapy than did those in the low-target group, but such therapy was not associated with a difference in mortality. Conclusions Targeting a mean arterial pressure of 80 to 85 mm Hg, as compared with 65 to 70 mm Hg, in patients with septic shock undergoing resuscitation did not result in significant differences in mortality at either 28 or 90 days. (Funded by the French Ministry of Health; SEPSISPAM number, NCT01149278 .).
    New England Journal of Medicine 03/2014; · 51.66 Impact Factor
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    ABSTRACT: On-admission coronary angiogram (CA) with angioplasty (percutaneous coronary intervention, PCI) may improve survival in patients resuscitated from out-of-hospital cardiac arrest (OHCA), but long-term survival data are scarce. We assessed long-term survival in OHCA patients managed with on-admission CA and PCI if indicated and compared survival rates in patients with/without acute coronary syndrome (ACS). Retrospective single-centre study including patients aged ≥18 years resuscitated from an OHCA without noncardiac cause, with sustained return of spontaneous circulation, undergoing on-admission CA with PCI if indicated. ACS was diagnosed angiographically. Survival was recorded at hospital discharge and at 5-year follow up. Survival probability was estimated by Kaplan-Meier survival curves. A total of 300 comatose patients aged 56 years (IQR 48-67 years) were included, 36% with ST-segment elevation. All had on-admission CA; 31% had ACS. PCI was attempted in 91% of ACS patients and was successful in 93%. Hypothermia was performed in 84%. Survival to discharge was 32.3%. After discharge, 5-year survival was 81.7±5.4%. Survival from admission to 5 years was 26.2±2.8%. ACS patients had better survival to discharge (40.8%) compared with non-ACS patients (28.5%, p=0.047). After discharge, 5-year survival was 92.2±5.4% for patients with ACS and 73.4±8.6% without ACS (hazard ratio, HR, 2.7, 95% CI 0.8-8.9, p=0.1). Survival from admission to 5 years was 37.4±5.2% for ACS patients, 20.7±3.0%, for non-ACS patients (HR 1.5, 95% CI 1.12-2.0, p=0.0067). OHCA patients undergoing on-admission CA had a very favourable postdischarge survival. Patients with OHCA due to ACS had better survival to discharge at 5-year follow up than patients with OHCA due to other causes.
    European heart journal. Acute cardiovascular care. 02/2014;
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    ABSTRACT: Drug fever (DF) is a febrile reaction induced by a drug without additional clinical features like skin eruption. This adverse drug reaction is probably common but under diagnosed. While its outcome is generally favourable, DF generates unnecessary diagnostic procedures as well as hospitalisations or hospitalisation prolongations. Clinical presentation and biological findings are not specific. Fever is generally well tolerated but may be accompanied by general symptoms mimicking sepsis. Moderate biological disorders could be expected, including elevation or decrease in white blood cell count, eosinophilia, liver cytolysis, and increased C-reactive protein. An infection should be systematically ruled out. Clinical or biological signs of severity should question DF diagnosis. When DF is suspected, the involved drug(s) should be stopped after a reliable assessment of imputability. Antibiotics represent the most often implicated drugs. Fever disappearance after discontinuing the suspected drug is the cornerstone of DF diagnosis. Before stopping the administration of the suspected drug(s), a risk/benefit ratio assessment is necessary. Consistently, it may be complicated to stop an antimicrobial drug when treating an infection or an immunosuppressive drug if required.
    La Revue de Médecine Interne. 01/2014; 35(3):183–188.
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    ABSTRACT: Background Pseudomonas aeruginosa is a major nosocomial pathogen in intensive care units (ICUs); however, endogenous versus exogenous origin of contamination remains unclear. Aim To identify individual and environmental ICU risk factors for P. aeruginosa acquisition. Methods A five-month prospective multicentric study was performed in ten French ICUs. Adult patients hospitalized in ICU for ≥24 h were included and screened for P. aeruginosa colonization on admission, weekly and before discharge. P. aeruginosa acquisition was defined by a subsequent colonization or infection if screening swabs on admission were negative. Water samples were obtained weekly on water taps of the ICUs. Data on patient characteristics, invasive devices exposure, antimicrobial therapy, P. aeruginosa water and patient colonization pressures, and ICU characteristics were collected. Hazard ratios (HRs) were estimated using multivariate Cox model. Findings Among the 1314 patients without P. aeruginosa on admission, 201 (15%) acquired P. aeruginosa during their ICU stay. Individual characteristics significantly associated with P. aeruginosa acquisition were history of previous P. aeruginosa infection or colonization, cumulative duration of mechanical ventilation and cumulative days of antibiotics not active against P. aeruginosa. Environmental risk factors for P. aeruginosa acquisition were cumulative daily ward ‘nine equivalents of nursing manpower use score’ (NEMS) [hazard ratio (HR): 1.47 for ≥30 points; 95% confidence interval (CI): 1.06–2.03] and contaminated tap water in patient’s room (HR: 1.76; CI: 1.09–2.84). Conclusion Individual risk factors and environmental factors for which intervention is possible were identified for P. aeruginosa acquisition.
    Journal of Hospital Infection. 01/2014;
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    ABSTRACT: Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P < 0.05) without altering minute volume (VE). In combination to DZP, BUP/NLX significantly increased expiratory time (P < 0.01) and decreased f (P < 0.01), tidal volume (VT, P < 0.001), and VE (P < 0.001) while BUP only decreased VT(P < 0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P < 0.001) and decreased f (P < 0.01) and VE (P < 0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined.
    Toxicology Letters 01/2014; · 3.15 Impact Factor
  • B. Mégarbane, D. Résière
    Annales francaises d'anesthesie et de reanimation 01/2014; · 0.77 Impact Factor
  • Maria Theodosiou, Arsia Amir-Aslani, Bruno Mégarbane
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    ABSTRACT: Regardless of stringent safety regulations and increased compound selectivity by pharmaceutical companies, prediction of toxicity in humans is still far from perfect and adverse drug reactions are still detected after drug marketing. High costs of failures due to toxicity has led pharmaceutical companies to search for screening methods that would allow detection of toxicity issues at an early stage and improve their preclinical and clinical toxicology. Thanks to the last decade's biotechnology revolution, new technologies like toxicogenomics have demonstrated the capacity to improve toxicity assessment. However, our understanding of toxicological mechanisms is still incomplete and a wide range of approaches must be used to gain insight into toxicity issues. Consequently, an array of in silico, in vitro and in vivo methods is utilized to predict toxicity and its causative mechanisms, improving drug development processes and minimizing costs of failure.
    Biotechnology Letters 11/2013; · 1.85 Impact Factor
  • B Mégarbane
    Annales francaises d'anesthesie et de reanimation 11/2013; · 0.77 Impact Factor
  • Journal of Emergency Medicine 11/2013; · 1.33 Impact Factor
  • Bruno Mégarbane, Lucie Chevillard
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    ABSTRACT: Damage to lungs may occur from systemic as well as inhalational exposure to various illegal drugs of abuse. Aspiration pneumonia probably represents the most common pulmonary complication in relation to consciousness impairment. Some pulmonary consequences may be specifically related to one given drug. Prolonged smoking of marijuana may result in respiratory symptoms suggestive of obstructive lung disease. Non-cardiogenic pulmonary edema has been attributed to heroin, despite debated mechanisms including attempted inspiration against a closed glottis, hypoxic damage to alveolar integrity, neurogenic vasoactive response to stress, and opiate-induced anaphylactoid reaction. Naloxone-related precipitated withdrawal resulting in massive sympathetic response with heart stunning has been mistakenly implicated. In crack users, acute respiratory syndromes called "crack-lung" with fever, hemoptysis, dyspnea, and pulmonary infiltration on chest X-rays have been reported up-to 48h after free-base cocaine inhalation, with features of pulmonary edema, interstitial pneumonia, diffuse alveolar hemorrhage, and eosinophil infiltration. The high-temperature of volatilized cocaine and the presence of impurities, as well as cocaine-induced local vasoconstriction have been suggested to explain alveolar damage. Some other drug-related pulmonary insults result from the route of drug self-administration. In intravenous drug users, granulomatous pneumonia with multinodular patterns on thoracic imaging is due to drug contaminants like talcum. Septic embolism from right-sided endocarditis represents an alternative diagnosis in case of sepsis from pulmonary origin. Following inhalation, pneumothorax, and pneumomediastinum have been attributed to increased intrathoracic pressure in relation to vigorous coughing or repeated Valsalva maneuvers, in an attempt to absorb the maximal possible drug amount. In conclusion, pulmonary consequences of illicit drugs are various, resulting in both acute life-threatening conditions and long-term functional respiratory sequelae. A better understanding of their spectrum and the implicated mechanisms of injury should help to improve patient management.
    Chemico-biological interactions 10/2013; · 2.46 Impact Factor
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    ABSTRACT: IMPORTANCE Despite advances in care, mortality and morbidity remain high in adults with acute bacterial meningitis, particularly when due to Streptococcus pneumoniae. Induced hypothermia is beneficial in other conditions with global cerebral hypoxia. OBJECTIVE To test the hypothesis that induced hypothermia improves outcome in patients with severe bacterial meningitis. DESIGN, SETTING, AND PATIENTS An open-label, multicenter, randomized clinical trial in 49 intensive care units in France, February 2009-November 2011. In total, 130 patients were assessed for eligibility and 98 comatose adults (Glasgow Coma Scale [GCS] score of ≤8 for <12 hours) with community-acquired bacterial meningitis were randomized. INTERVENTIONS Hypothermia group received a loading dose of 4°C cold saline and were cooled to 32°C to 34°C for 48 hours. The rewarming phase was passive. Controls received standard care. MAIN OUTCOMES AND MEASURES Primary outcome measure was the Glasgow Outcome Scale score at 3 months (a score of 5 [favorable outcome] vs a score of 1-4 [unfavorable outcome]). All patients received appropriate antimicrobial therapy and vital support. Analyses were performed on an intention-to-treat basis. The data and safety monitoring board (DSMB) reviewed severe adverse events and mortality rate every 50 enrolled patients. RESULTS After inclusion of 98 comatose patients, the trial was stopped early at the request of the DSMB because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51%]) vs the control group (15 of 49 patients [31%]; relative risk [RR], 1.99; 95% CI, 1.05-3.77; P = .04). Pneumococcal meningitis was diagnosed in 77% of patients. Mean (SD) temperatures achieved 24 hours after randomization were 33.3°C (0.9°C) and 37.0°C (0.9°C) in the hypothermia and control group, respectively. At 3 months, 86% in the hypothermia group compared with 74% of controls had an unfavorable outcome (RR, 2.17; 95% CI, 0.78-6.01; P = .13). After adjustment for age, score on GCS at inclusion, and the presence of septic shock at inclusion, mortality remained higher, although not significantly, in the hypothermia group (hazard ratio, 1.76; 95% CI, 0.89-3.45; P = .10). Subgroup analysis on patients with pneumococcal meningitis showed similar results. Post hoc analysis showed a low probability to reach statistically significant difference in favor of hypothermia at the end of the 3 planned sequential analyses (probability to conclude in favor of futility, 0.977). CONCLUSIONS AND RELEVANCE Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Careful evaluation of safety issues in future trials on hypothermia are needed and may have important implications in patients presenting with septic shock or stroke. TRIAL REGISTRATION Identifier: NCT00774631.
    JAMA The Journal of the American Medical Association 10/2013; · 29.98 Impact Factor
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    ABSTRACT: AIMS: To assess long-term outcomes and the management of critical left-sided infective endocarditis (IE) and evaluate the impact of surgery. METHODS AND RESULTS: Among the 198 patients included prospectively for IE across 33 adult intensive care units (ICU) in France from 1 April 2007 to 1 October 2008, 137 (69%) were dead at a median follow-up time of 59.5 months. Characteristics significantly associated with mortality were: Sepsis-related Organ-Failure Assessment (SOFA) score at ICU admission [Hazard ratio (HR), 95% Confidence Interval (CI) of 1.43 (0.79-2.59) for SOFA 5-9; 2.01 (1.05-3.85) for SOFA 10-14; 3.53 (1.75-7.11) for SOFA 15-20; reference category SOFA 0-4; P = 0.003]; prosthetic mechanical valve IE [HR 2.01; 95% CI 1.09-3.69, P = 0.025]; vegetation size ≥15 mm [HR 1.64; 95% CI 1.03-2.63, P = 0.038]; and cardiac surgery [HR (95%CI), 0.33 (0.16-0.67) for surgery ≤1 day after IE diagnosis; 0.61 (0.29-1.26) for surgery 2-7 days after IE diagnosis; 0.42 (0.21-0.83) for surgery >7 days after IE diagnosis; reference category no surgery; P = 0.005]. One hundred and three (52%) patients underwent cardiac surgery after a median time of 6 (16) days. Independent predictors of surgical intervention on multivariate analysis were: age ≤60 years [Odds ratio (OR) 5.30; 95% CI (2.46-11.41), P < 0.01], heart failure [OR 3.27; 95% CI (1.03-10.35), P = 0.04], cardiogenic shock [OR 3.31; 95% CI (1.47-7.46), P = 0.004], septic shock [OR 0.25; 95% CI (0.11-0.59), P = 0.002], immunosuppression [OR 0.15; 95% CI (0.04-0.55), P = 0.004], and diagnosis before or within 24 h of ICU admission [OR 2.81; 95% CI (1.14-6.95), P = 0.025]. SOFA score calculated the day of surgery was the only independently associated factor with long-term mortality [HR (95% CI) 1.59 (0.77-3.28) for SOFA 5-9; 3.56 (1.71-7.38) for SOFA 10-14; 11.58 (4.02-33.35) for SOFA 15-20; reference category SOFA 0-4; P < 0.0001]. Surgical timing was not associated with post-operative outcomes. Of the 158 patients with a theoretical indication for surgery, the 58 deemed not fit had a 95% mortality rate. CONCLUSION: Mortality in patients with critical IE remains unacceptably high. Factors associated with long-term outcomes are the severity of multiorgan failure, prosthetic mechanical valve IE, vegetation size ≥15 mm, and surgical treatment. Up to one-third of potential candidates do not undergo surgery and these patients experience extremely high mortality rates. The strongest independent predictor of post-operative mortality is the pre-operative multiorgan failure score while surgical timing does not seem to impact on outcomes.
    European Heart Journal 08/2013; · 14.10 Impact Factor
  • Katell Peoc'h, Bruno Megarbane
    Journal of medical toxicology: official journal of the American College of Medical Toxicology 07/2013;
  • B Mégarbane, H Alhaddad
    BJA British Journal of Anaesthesia 05/2013; 110(5):842. · 4.24 Impact Factor

Publication Stats

2k Citations
878.41 Total Impact Points


  • 2007–2014
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2001–2014
    • Hôpital Ambroise Paré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Billancourt, Île-de-France, France
  • 2013
    • Grenoble École de Management
      Grenoble, Rhône-Alpes, France
    • University of Utah
      • Division of Emergency Medicine
      Salt Lake City, UT, United States
  • 2006–2013
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • University of Otago
      • Department of Preventive & Social Medicine
      Dunedin, Otago, New Zealand
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      Lutetia Parisorum, Île-de-France, France
  • 2009–2011
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2002–2011
    • Assistance Publique – Hôpitaux de Paris
      • Department of Cardiology
      Paris, Ile-de-France, France
  • 2010
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Caen
      Caen, Lower Normandy, France
  • 2008–2010
    • University of Nebraska Medical Center
      • Department of Pathology and Microbiology
      Omaha, Nebraska, United States
  • 2003–2010
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2005–2007
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2000–2001
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      • Service de Réanimation Médicale et des Maladies Infectieuses
      Lutetia Parisorum, Île-de-France, France