Incidence of Pneumocystis jiroveci Pneumonia among Groups at Risk in HIV-negative Patients

International audienceBackground - Pneumocystis jiroveci pneumonia in human immunodeficiency virus (HIV)-negative immunocompromised patients is associated with high mortality rates. Although trimethoprim-sulfamethoxazole provides a very effective prophylaxis, pneumocystosis still occurs and may even be emerging due to suboptimal characterization of patients most at risk, hence precluding targeted prophylaxis. Methods - We retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted in our institution, a referral center in the area, from January 1990 to June 2010, and extracted data on their underlying condition(s). To estimate incidence rates within each condition, we estimated the number of patients followed-up in our area for each condition by measuring the number of patients admitted with the corresponding international classification diagnostic code, through the national hospital discharge database (Program of Medicalization of the Information System [PMSI]). Results - From 1990 to 2010, 293 cases of pneumocystosis were documented, of which 154 (52.6%) tested negative for HIV. The main underlying conditions were hematological malignancies (32.5%), solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in 3 categories: 1) high risk (incidence rates >45 cases per 100,000 patient-year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma; 2) intermediate risk (25-45 cases per 100,000 patient-year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and 3) low risk (<25 cases per 100,000 patient-year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma. Conclusions - These estimates may be used as a guide to better target pneumocystosis prophylaxis in the groups most at risk

Constipation is independently associated with delirium in critically ill ventilated patients

International audienceDelirium is a central nervous system (CNS) dysfunction reported in up to 80 % of intensive care unit (ICU) patients associated with negative short- and long-term outcomes [1, 2]. Gastrointestinal motility disorders are frequent in ICU patients leading to frequent delayed passage of stools [3]. Because there is a bi-directional communication between the CNS and the digestive tract [4], we believed it relevant to test the hypothesis that constipation and delirium are related in ICU patients

Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study.

BACKGROUND: The presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP. METHODS: This was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients. RESULTS: Among 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone. CONCLUSION: Bacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors

Déterminants et conséquences de l'Emergence des souches communautaires de Staphylococcus Aureus résistant à la Meticilline

Staphylococcus Aureus résistants à la méticilline (SARM) est longtemps resté confiné au secteur hospitalier à la suite des premières descriptions, en 1962. La diffusion des SARM communautaires à partir de 1993 a eu des conséquences sévères en termes de santé publique. Un clone en particulier, USA300, a diffusé rapidement dans la population générale et les hôpitaux. Dans le premier volet de cette thèse (physiopathologie), nous démontrons que la leucocidine de Panton-Valentine est associée, chez le lapin, à une dissémination plus importante de l'infection dans un modèle de batériémie à SARM et à des pneumopathies plus sévères en cas d'inoculation intra-trachéale. Dans le second volet (épidemiologie), nous documentons l'émergence d'USA300 dans le principal centre de long séjour de San Francisco (épicentre de l'épidemie USA300) et dans les prisons. Dans le troisième volet (thérapeutique), nous testons de nouvellesoptions dans le modèle d'endocardite du lapin : daptomycine et ceftobiproleRENNES1-BU Santé (352382103) / SudocSudocFranceF

Dysfonctions monocytaires et activité indoléamine 2,3-dioxygénase au cours du choc septique

Le choc septique s'accompagne d'altérations monocytaires et d'une augmentation de l'activité IDO systémique. Le compartiment myéloïde circulant a été étudié par cytométrie en flux chez 14 patients atteints de choc septique et 23 volontaires sains. L'arginase 1 plasmatique a été dosée par ELISA chez des patients atteints de sepsis (n=68), cancers (n=7) et volontaires sains (n=9). La prolifération des cellules sanguines mononucléées (CMN) totales ou déplétées en cellules CD14+ a été testée in vitro. Le nombre de monocytes CD14+CD16+ et CD14+HLA-DR10/- est augmenté chez les patients septiques. Le nombre de monocytes CD14dimCD16+ est diminué. L'arginase 1 est plus élevée chez certains patients septiques et non corrélée à l'activité IDO. La déplétion des cellules CD14+ restaure partiellement la prolifération des CMN de patients septiques. La répartition des sous-populations monocytaires est perturbée au cours du choc septique et pourrait traduire l'acquisition d'un phénotype MDSC.Septic shock-associated immune dysfonction is characterized by monocyte alterations and enhanced IDO activity. Blood myeloid cells were studied by flow cytometry in 23 patients with septic shock and 14 healthy donors. Arginase 1 plasma levels were measured by ELISA in patients with septic shock (n=68), cancer (n=7) and healthy donors (n=9). Total and CD14-depleted peripheral blood mononuclear cells (PBMC) proliferation was assayed in vitro. CD14+CD16+ and CD14+HLA-DR10/- monocytes are increased whereas CD14dimCD16+ monocytes are decreased in septic patients. Plasmatic arginase 1 level is increased in some but not all septic patients. Depletion of CD14+ cells partially restores the proliferation of PBMC from septic patients. Monocyte subpopulations are imbalanced during septic shock and may reflect the acquisition of a MDSC phenotype.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Réponses immunitaires locales et systémiques au cours de l'agression aiguë

RENNES1-BU Santé (352382103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Toward new insights on the white blood cell differential by flow cytometry: A proof of concept study on the sepsis model

International audienceBackground:We sought to evaluate, on a model of sepsis, the clinical relevance of new parameters obtained on a white blood cell (WBC) differential by flow cytometry, implemented in the routine workflow of our hematology laboratory.Methods:A WBC with differential by flow cytometry was done on 459 patients at admission in intensive care unit. They were retrospectively categorized in having (i) infection or not or (ii) a high gravity score (severe sepsis or septic shock) or not. We analyzed by hierarchical clustering, in a multidimensional manner, 50 parameters provided by the flow cytometric platform in place of the standard seven parameters for a standard differential.Results:Our approach allows to discriminate on the basis of a WBC differential (i) infected patients at admission based on a 16 parameter signature, with a concordance rate of 72.7% and a specificity of 79.9% and (ii) patients with high gravity score (septic shock or severe sepsis) at admission with a signature of eight parameters, with a concordance rate of 74.7% and a specificity of 75.9%.Conclusions:This study shows the clinical relevance of an extended WBC differential to obtain by a flow cytometer integrated into a routine hematology laboratory workflow. Development of such approach implicates the redefinition of the WBC differential by integrating new parameters. © 2012 International Clinical Cytometry Societ

Incidence and risk factors for acquired colonization and infection due to extended-spectrum beta-lactamase-producing Gram-negative bacilli a retrospective analysis in three ICUs with low multidrug resistance rate

International audienceThe purpose of this study is to assess risk factors for the acquisition of extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) colonization and infection (AI) in ICUs with low ESBL-GNB prevalence rate. We conducted a retrospective observational study in three ICUs in Bretagne, France. All patients admitted from January 2016 to September 2017 with a length of stay of 2 days or more were included. Universal screening for ESBL-GNB colonization was performed in all participating ICUs. Of the 3250 included patients, 131 (4.0%) were colonized at admission, 59 acquired colonization while hospitalized (1.9%; 95% CI [1.5-2.5%]), and 15 (0.5%; 95% CI [0.3-0.8%]) acquired ESBL-GNB infections. In the case of infection, the specificity and the negative predictive values of preexistent colonization for the ESBL-GNB etiology were 93.2% [91.5-95.1%] and 95.2% [93.5-97.1%], respectively. Colonization was the main risk factor for ESBL-GNB AI (OR = 9.61; 95% CI [2.86-32.29]; p < 0.001). Antimicrobial susceptibility of non-ESBL-GNB isolates responsible for AI was similar for any non-carbapenem β-lactam (95%) and imipenem (94%). ESBL-GNB AIs were rare in ICUs with low ESBL-GNB prevalence rate. Prior colonization was the main risk factor for subsequent infection. Empirical carbapenem therapy could be avoided in non ESBL-GNB colonized patients with suspected AI