Yohann Dubois

University of Grenoble, Grenoble, Rhône-Alpes, France

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Publications (6)26.86 Total impact

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    ABSTRACT: Virulence of Pseudomonas aeruginosa is typically attributed to its type III secretion system (T3SS). A taxonomic outlier, the P. aeruginosa PA7 strain, lacks a T3SS locus, and no virulence phenotype is attributed to PA7. We characterized a PA7-related, T3SS-negative P. aeruginosa strain, CLJ1, isolated from a patient with fatal hemorrhagic pneumonia. CLJ1 is highly virulent in mice, leading to lung hemorrhage and septicemia. CLJ1-infected primary endothelial cells display characteristics of membrane damage and permeabilization. Proteomic analysis of CLJ1 culture supernatants identified a hemolysin/hemagglutinin family pore-forming toxin, Exolysin (ExlA), that is exported via ExlB, representing a putative two-partner secretion system. A recombinant P. aeruginosa PAO1ΔpscD::exlBA strain, deficient for T3SS but engineered to express ExlA, gained lytic capacity on endothelial cells and full virulence in mice, demonstrating that ExlA is necessary and sufficient for pathogenicity. This highlights clinically relevant T3SS-independent hypervirulence, isolates, and points to a broader P. aeruginosa pathogenic repertoire.
    Cell host & microbe 02/2014; 15(2):164-76. · 13.02 Impact Factor
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    ABSTRACT: We evaluated the respective influence of the causative pathogen and infection site on hospital mortality from severe sepsis related to community-, hospital-, and intensive care unit-acquired infections. We used a prospective observational cohort 10-yr database. We built a subdistribution hazards model with corrections for competing risks and adjustment for potential confounders including early appropriate antimicrobial therapy. Twelve intensive care units. We included 4,006 first episodes of acquisition-site-specific severe sepsis in 3,588 patients. INTEVENTIONS: None. We included 1562 community-acquired, 1432 hospital-acquired, and 1012 intensive care unit-acquired episodes of severe sepsis. After adjustment, we found no independent associations of the causative organism, multidrug resistance of the causative organism, infection site, or presence of bacteremia with mortality. Early appropriate antimicrobial therapy was consistently associated with better survival in the community-acquired (0.64 [0.51-0.8], p = .0001), hospital-acquired (0.72 [0.58-0.88], p = .0011), and intensive care unit-acquired (0.79 [0.64-0.97], p = .0272) groups. The infectious process may not exert as strong a prognostic effect when severity, organ dysfunction and, above all, appropriateness of early antimicrobials are taken into account. Our findings emphasize the importance of developing valid recommendations for early antimicrobial therapy.
    Critical care medicine 04/2011; 39(8):1886-95. · 6.37 Impact Factor
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    ABSTRACT: Although Pseudomonas aeruginosa is a leading pathogen responsible for ventilator-associated pneumonia (VAP), the excess in mortality associated with multi-resistance in patients with P. aeruginosa VAP (PA-VAP), taking into account confounders such as treatment adequacy and prior length of stay in the ICU, has not yet been adequately estimated. A total of 223 episodes of PA-VAP recorded into the Outcomerea database were evaluated. Patients with ureido/carboxy-resistant P. aeruginosa (PRPA) were compared with those with ureido/carboxy-sensitive P. aeruginosa (PSPA) after matching on duration of ICU stay at VAP onset and adjustment for confounders. Factors associated with onset of PRPA-VAP were as follows: admission to the ICU with septic shock, broad-spectrum antimicrobials at admission, prior use of ureido/carboxypenicillin, and colonization with PRPA before infection. Adequate antimicrobial therapy was more often delayed in the PRPA group. The crude ICU mortality rate and the hospital mortality rate were not different between the PRPA and the PSPA groups. In multivariate analysis, after controlling for time in the ICU before VAP diagnosis, neither ICU death (odds ratio (OR) = 0.73; 95% confidence interval (CI): 0.32 to 1.69; P = 0.46) nor hospital death (OR = 0.87; 95% CI: 0.38 to 1.99; P = 0.74) were increased in the presence of PRPA infection. This result remained unchanged in the subgroup of 87 patients who received adequate antimicrobial treatment on the day of VAP diagnosis. After adjustment, and despite the more frequent delay in the initiation of an adequate antimicrobial therapy in these patients, resistance to ureido/carboxypenicillin was not associated with ICU or hospital death in patients with PA-VAP.
    Critical care (London, England) 04/2011; 15(2):R112. · 4.72 Impact Factor
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    ABSTRACT: Catheters are the leading source of bloodstream infections in critically ill patients. Because the clinical signs of infection are nonspecific, such infections are overly suspected, which results in unnecessary removal of catheters. A conservative approach might be attempted in mild infections, whereas catheters should always be removed in cases of severe sepsis or septic shock. Nowadays, comprehensive unit-based improvement programs are effective to reduce catheter-related bloodstream infections (CR-BSIs). Rates of CR-BSI higher than 2 per 1000 catheter-days are no longer acceptable. A locally adapted checklist of preventive measures should include cutaneous antisepsis with alcoholic preparation, maximal barrier precaution, strict policy of catheter maintenance, and ablation of useless catheters. Antiseptic dressings and, to a lesser extent, antimicrobial-coated catheters, might be added to the prevention strategies if the level of infections remains high despite implementation of a prevention program. In the case of CR-BSI in intensive care units (ICUs), the catheter should be removed. In the case of persistence of fever or positive blood cultures after 3 days, inadequate antibiotic therapy, endocarditis, or thrombophlebitis should be ruled out.
    Seminars in Respiratory and Critical Care Medicine 04/2011; 32(2):139-50. · 2.75 Impact Factor
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    ABSTRACT: Catheters are the leading source of bloodstream infections for patients in the intensive care unit (ICU). Comprehensive unit-based programs have proven to be effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable. The locally adapted list of preventive measures should include skin antisepsis with an alcoholic preparation, maximal barrier precautions, a strict catheter maintenance policy, and removal of unnecessary catheters. The development of new technologies capable of further decreasing the now low CR-BSI rate is a major challenge. Recently, new materials that decrease the risk of skin-to-vein bacterial migration, such as new antiseptic dressings, were extensively tested. Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent bacterial migration from the hub to the bloodstream. This review discusses the available knowledge about these new technologies.
    Annals of intensive care. 01/2011; 1:34.
  • Yohann Dubois, Jean-françois Timsit
    La Revue du praticien 12/2008; 58(17):1929-34.