Florence Ader

CHU de Lyon - Hôpital de la Croix-Rousse, Lyons, Rhône-Alpes, France

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Publications (57)133.87 Total impact

  • Case Reports 11/2014; 2014.
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    ABSTRACT: Introduction: The incomplete immune recovery upon effective long-term highly active antiretroviral therapy (HAART) has been associated with increased morbidity and mortality in HIV infected patients [1]. Immune cellular activation, Tregs or very low-level viraemia has been alternatively suspected, but never investigated simultaneously [2]. Materials and Methods: We performed a cross-sectional study in 87 aviraemic patients (men=62, mean CD4+T cells=570/mm(3), mean duration of HAART=12 years). Patients with at least 500 CD4+ T cells /mm(3) were classified as complete immunological responders (cIR), whereas remaining patients were classified as inadequate immunological responder (iIR). Tregs were characterized based on CD4+CD25highFoxP3+phenotype using a one-step intracellular staining. Effector Tregs and terminal effectors Tregs were respectively defined as CD4+CD25+FoxP3+CD45RA-, and CD4+CD25+FoxP3+CD45RA-HLADR+phenotypes as recently described [3]. Activated T cells were identified using (i) elevated HLA-DR expression for CD4+T cells, and (ii) increased expressions of HLA-DR, or CD38, or both (HLADR+CD38+cells) for CD8+T cells. Very low-level viraemia was defined as detectable viraemia between 1 and 39 cp/mL. Univariate and multivariate analyses were performed to identify determinants of iIR. Results: Thirty-nine patients were classified as iIR, and 48 as cIR. Patients from the iIR group were significantly older (55 vs 50 years, p=0.027), and had percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs significantly higher (5.3 vs 4%, p=0.014; 9 vs 7.5%, p=0,022; 8 vs 6.3%, p=0.01 and 1.8 vs 1.3%, p=0,033 among CD4+T cells, respectively). Neither the percentage of activated CD8+T cell nor very low-level viraemia were found to be associated with iIR. In the multivariate analysis, nadir of CD4+T cell count and percentage of Tregs were the only two parameters independently associated with iIR (OR=2.339, p=0.001, and OR=0.803, p=0.041, respectively). Conclusions: We present here the largest study investigating simultaneously immune response to long-term HAART, immune activation of CD4+ and CD8+ T cells, Tregs percentages and very low-level viraemia. Our results highlight the importance of Tregs in CD4 homeostasis. This aspect should now be prospectively explored in a large cohort of patients.
    Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19672. · 4.21 Impact Factor
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    ABSTRACT: The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant Herpes Simplex Virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5-10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002-2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002-2006 (7/182 patients) to 15.7% between 2007-2011 (28/178) (p=0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002-2006 to 46.5% (26/56) between 2007-2011 (p=0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance.
    Antiviral Research 11/2014; · 3.43 Impact Factor
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    ABSTRACT: Although methicillin-susceptible Staphylococcus aureus (MSSA) native bone and joint infection (BJI) constitutes the more frequent clinical entity of BJI, prognostic studies mostly focused on methicillin-resistant S. aureus prosthetic joint infection. We aimed to assess the determinants of native MSSA BJI outcomes.
    BMC Infectious Diseases 08/2014; 14(1):443. · 2.56 Impact Factor
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    ABSTRACT: Several vaccines are recommended in HIV-infected patients due to an increased risk of vaccine-preventable infections, severe forms of the disease, or shared transmission routes. Few data are available regarding vaccination coverage and its determinants in this population.
    Vaccine 06/2014; · 3.49 Impact Factor
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    ABSTRACT: BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.Bone Marrow Transplantation advance online publication, 3 February 2014; doi:10.1038/bmt.2013.235.
    Bone marrow transplantation 02/2014; · 3.00 Impact Factor
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    ABSTRACT: Prolonged antimicrobial therapy is recommended for methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10-year increase; 95% confidence interval [CI], 1.116 to 1.960; P = 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051; P = 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627; P = 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients.
    Antimicrobial Agents and Chemotherapy 02/2014; 58(2). · 4.57 Impact Factor
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    ABSTRACT: IntroductionThe mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active antiretroviral therapy remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viremia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. Materials and Methods We performed a cross sectional study in HIV-infected aviremic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters independently associated with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39) depending on CD4+ T cell count (> or < 500/mm3). Clinical and virological data (including very low level viremia) were collected. In parallel, immunophenotyping of CD4+ lymphocytes, including Tregs subsets, and CD8+ T cells was performed. ResultsPercentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4+ T cell count and percentage of Tregs were the only two parameters independently associated with iIR (OR=2.339, p=0.001, and OR=0.803, p=0.041). Conclusion We present here the largest study investigating simultaneously immune response to long-term HAART, activation of CD4+ and CD8+ T cells, Tregs percentages and very low-level viremia. Causative interactions between Tregs and CD4+ T cells should now be prospectively explored in a large cohort of patients.
    Clinical & Experimental Immunology 01/2014; · 3.28 Impact Factor
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    ABSTRACT: Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Physicians must be aware of typical clinical presentations (such as cervicofacial actinomycosis following dental focus of infection, pelvic actinomycosis in women with an intrauterine device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are necessary to identify the bacterium and typical microscopic findings include necrosis with yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the duration of antimicrobial therapy could probably be shortened to 3 months in patients in whom optimal surgical resection of infected tissues has been performed. Preventive measures, such as reduction of alcohol abuse and improvement of dental hygiene, may limit occurrence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic actinomycosis.
    Infection and Drug Resistance 01/2014; 7:183-97.
  • Case Reports 03/2013; 2013.
  • Médecine et Maladies Infectieuses 01/2013; · 0.91 Impact Factor
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    ABSTRACT: Microglial cells constitute the first line of defense of the central nervous system (CNS) against microbial invasion. Pathogens are detected thanks to an array of innate immune receptors termed pattern recognition receptors (PRRs). PRRs have been thoroughly characterized in bone marrow-derived macrophages, but the PRRs repertoire and functionality in microglial cells remain largely unknown. Microglial cells express various Toll-like Receptors and the Nod1/2 receptors. Recently, a novel innate immune signalling pathway, the inflammasome pathway has been uncovered. Inflammasome activation leads to caspase-1 activation, release of the proinflammatory cytokines, IL-1β and IL-18 and cell death in a process termed pyroptosis. One inflammasome receptor, NLRP3, has been characterized in microglial cells and associated with response to infections and in the initiation of neuro-degeneration in an Alzheimer's disease model. Legionella pneumophila (L.pneumophila) is a flagellated bacterium replicating within macrophages. In bone marrow-derived macrophages, L. pneumophila is detected in a flagellin-dependent manner by the Naip5-NLRC4 (Ipaf) inflammasome pathway. In this study, we decided to use L. pneumophila to investigate the presence and the functionality of this inflammasome in primary murine microglial cells. We show that microglial cells detect L. pneumophila infection in a flagellin-dependent manner leading to caspase-1-mediated bacterial growth restriction, infected cell death and secretion of the proinflammatory cytokines IL-1β and IL18. Overall, our data demonstrate that microglial cells have a functional Naip5-NLRC4 inflammasome likely to be important to monitor and clear CNS infections by flagellated bacteria. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.
    Glia 01/2013; · 5.47 Impact Factor
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    ABSTRACT: The inflammasome is an innate immune signaling platform leading to caspase-1 activation, maturation of pro-inflammatory cytokines and cell death. Recognition of DNA within the host cytosol induces the formation of a large complex composed of the AIM2 receptor, the ASC adaptor and the caspase-1 effector. Francisella tularensis, the agent of tularemia, replicates within the host cytosol. The macrophage cytosolic surveillance system detects Francisella through the AIM2 inflammasome. Upon Francisella novicida infection, we observed a faster kinetics of AIM2 speck formation in ASC(KO) and Casp1(KO) as compared to WT macrophages. This observation was validated by a biochemical approach thus demonstrating for the first time the existence of a negative feedback loop controlled by ASC/caspase-1 that regulates AIM2 complex formation/stability. This regulatory mechanism acted before pyroptosis and required caspase-1 catalytic activity. Our data suggest that sublytic caspase-1 activity could delay the formation of stable AIM2 speck, an inflammasome complex associated with cell death.
    Frontiers in Cellular and Infection Microbiology 01/2013; 3:14. · 2.62 Impact Factor
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    ABSTRACT: Legionella is the causative agent of Legionnaires' disease, a severe form of pneumonia. Detection of Legionella pneumophila serogroup 1 antigen in urine samples has shortened the delay of diagnosis and subsequent treatment initiation resulting in decreased mortality. Improved surveillance of potable water system reinforces the community prevention. In France, the National Reference Center for Legionella collects the strains responsible for sporadic or epidemic cases and crosslinks the data including epidemiological pattern, clinical presentation, and genetic analysis of the strains. Regarding host-pathogen interactions, major advances have been made recently in the understanding of L. pneumophila ability to subvert the host intracellular trafficking and the innate immune response leading to infection control.
    Medecine sciences: M/S 06/2012; 28(6-7):639-45. · 0.52 Impact Factor
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    ABSTRACT: We evaluated the contribution of amoebic coculture to the recovery of Legionella spp. from 379 respiratory samples. The sensitivity of axenic culture was 42.1%. The combination of axenic culture with amoebic coculture increased the Legionella isolation rate to 47.1%. Amoebic coculture was particularly efficient in isolating Legionella spp. from respiratory samples contaminated with oropharyngeal flora.
    Journal of clinical microbiology 02/2012; 50(5):1725-6. · 4.23 Impact Factor
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    ABSTRACT: The aim of the present study was to detect the Staphylococcus aureus delta-toxin using Whole-Cell (WC) Matrix Assisted Laser Desorption Ionization-Time-of-Flight (MALDI-TOF) mass spectrometry (MS), correlate delta-toxin expression with accessory gene regulator (agr) status, and assess the prevalence of agr deficiency in clinical isolates with and without resistance to methicillin and glycopeptides. The position of the delta-toxin peak in the mass spectrum was identified using purified delta-toxin and isogenic wild type and mutant strains for agr-rnaIII, which encodes delta-toxin. Correlation between delta-toxin production and agr RNAIII expression was assessed by northern blotting. A series of 168 consecutive clinical isolates and 23 unrelated glycopeptide-intermediate S. aureus strains (GISA/heterogeneous GISA) were then tested by WC-MALDI-TOF MS. The delta-toxin peak was detected at 3005±5 Thomson, as expected for the naturally formylated delta toxin, or at 3035±5 Thomson for its G10S variant. Multivariate analysis showed that chronicity of S. aureus infection and glycopeptide resistance were significantly associated with delta-toxin deficiency (p = 0.048; CI 95%: 1.01-10.24; p = 0.023; CI 95%: 1.20-12.76, respectively). In conclusion, the S. aureus delta-toxin was identified in the WC-MALDI-TOF MS spectrum generated during routine identification procedures. Consequently, agr status can potentially predict infectious complications and rationalise application of novel virulence factor-based therapies.
    PLoS ONE 01/2012; 7(7):e40660. · 3.53 Impact Factor
  • Christian Chidiac, Florence Ader
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    ABSTRACT: Community-acquired pneumonia are potentially life threatening infections for which accurate diagnosis and adequate antibiotic treatment are mandatory. S. pneumoniae remains the first bacterial agent and, is responsible, with L. pneumophila of most of fatal issues. Analysis of risk factors and severity signs by practitionners is required to properly manage such infections, Microbiological documentation is scarce in ambulatory medecine and account for less than 50% of hospitalised patients; thus, antibiotic treatment is empirical in most of cases. Amoxicillin remains drug of choice for ambulatory or hospitalized patients without risk factors or severity signs in medical wards, pristinamycin is recommended when an atypical agent cannot be rule out. Respiratory quinolone, mainly levofloxacin, can be prescribed in high risk patients, or in case of a failure of a first line of treatment.
    La Revue du praticien 10/2011; 61(8):1077-84.
  • International journal of antimicrobial agents 08/2011; 38(2):188-9. · 3.03 Impact Factor
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    ABSTRACT: Pseudomonas aeruginosa is a frequent cause of ventilator-acquired pneumonia (VAP). Candida tracheobronchial colonization is associated with higher rates of VAP related to P. aeruginosa. This study was designed to investigate whether prior short term Candida albicans airway colonization modulates the pathogenicity of P. aeruginosa in a murine model of pneumonia and to evaluate the effect of fungicidal drug caspofungin. BALB/c mice received a single or a combined intratracheal administration of C. albicans (1 × 10(5) CFU/mouse) and P. aeruginosa (1 × 10(7) CFU/mouse) at time 0 (T0) upon C. albicans colonization, and Day 2. To evaluate the effect of antifungal therapy, mice received caspofungin intraperitoneally daily, either from T0 or from Day 1 post-colonization. After sacrifice at Day 4, lungs were analyzed for histological scoring, measurement of endothelial injury, and quantification of live P. aeruginosa and C. albicans. Blood samples were cultured for dissemination. A significant decrease in lung endothelial permeability, the amount of P. aeruginosa, and bronchiole inflammation was observed in case of prior C. albicans colonization. Mortality rate and bacterial dissemination were unchanged by prior C. albicans colonization. Caspofungin treatment from T0 (not from Day 1) increased their levels of endothelial permeability and lung P. aeruginosa load similarly to mice receiving P. aeruginosa alone. P. aeruginosa-induced lung injury is reduced when preceded by short term C. albicans airway colonization. Antifungal drug caspofungin reverses that effect when used from T0 and not from Day 1.
    Critical care (London, England) 06/2011; 15(3):R150. · 5.04 Impact Factor
  • Thomas Baudry, Florence Ader
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    ABSTRACT: Several forms of supportive techniques for respiration in intensive care units (ICU) are currently available. The most widely used is invasive mechanical ventilation through the use of an endotracheal tube (ETT). ETTs are proved to be important contributors to the pathogenesis and development of ventilator-acquired pneumonia (VAP) as artificial airways interfere with a number of respiratory tract defence mechanisms and facilitate bacterial colonisation of the tracheobronchial tree. The occurrence of VAP is known to be one of the leading cause of morbidity and mortality in ICUs. On that basis, non-invasive techniques have been developed through the use of patient-ventilator interfaces in the form of facial masks which allow the development of ventilatory modalities working in synchrony with the patient. The purpose of this review is to examine the impact of non-invasive ventilation on the occurrence of ICU-acquired infections, most likely VAP, when used as an alternative for endotracheal intubation or when applied after early extubation. Regarding the reduction of endotracheal intubation, many studies have confirmed the net benefit of using non-invasive ventilation, mostly in chronic obstructive pulmonary diseases with acute hypercapnic ventilatory failure, in cardiogenic pulmonary edema, and in selected populations such as immunocompromised patients. Additionally, some studies have demonstrated a substantial benefit on hospital mortality. Early extubation with immediate application of non-invasive ventilation as a method to wean patients from invasive ventilation has shown a significant effect on hospital mortality. Overall, in our experience, patients with chronic obstructive pulmonary disease with hypercapnic acute respiratory failure are most likely benefiting from non-invasive ventilation either in the acute setting or during the immediate post-extubation phase. Acute cardiogenic patients must also receive primary respiratory non-invasive support. For immunocompromised patients, given the broad range of immunosuppression settings, the underlying condition should guide the decision of applying non-invasive support or not in a case by case approach.
    Infectious disorders drug targets. 06/2011; 11(4):384-8.

Publication Stats

427 Citations
133.87 Total Impact Points


  • 2010–2014
    • CHU de Lyon - Hôpital de la Croix-Rousse
      Lyons, Rhône-Alpes, France
    • Dana-Farber Cancer Institute
      • Department of Cancer Immunology and AIDS
      Boston, Massachusetts, United States
  • 2009–2014
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
    • CHU de Lyon - Hôpital Gériatrique Antoine Charial 
      Lyons, Rhône-Alpes, France
  • 2008–2013
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
    • Laboratoire de Recherche en Informatique
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • HCL
      Noida, Uttar Pradesh, India
  • 2008–2011
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2005–2008
    • Centre Hospitalier Régional Universitaire de Lille
      • Intensive Care Unit
      Lille, Nord-Pas-de-Calais, France
    • Centre hospitalier Gustave Dron
      Tourcoing, Nord-Pas-de-Calais, France
  • 2007
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France