ASPERGILLOSE INVASIVE EN HEMATOLOGIE : DE L ENVIRONNEMENT AU PATIENT (à propos de l'étude épidémiologique et clinique des cas d'aspergillose invasive observés en unité de soins intensifs d'hématologie au centre hospitalier de Versailles)

L Aspergillose invasive (AI) est une maladie grave, dont la létalité est importante chez les patients d hématologie. La précocité du diagnostic influe sur la stratégie thérapeutique et de fait le pronostic. Deux études ont été réalisées au Centre Hospitalier de Versailles en 2009 et 2010. La première s est intéressée aux outils diagnostiques, le plus utilisé étant la détection de l antigène Galactomannane. Les faux positifs en Galactomannane sont connus tels que l association Pipéracilline-Tazobactam (PT), principal antibiotique utilisé en hématologie. L étude a été conduite chez la totalité des patients en aplasie hospitalisés en Soins Intensifs d hématologie (USI) et en unité d hématologie conventionnelle. Ce travail suggère que l association entre faux-positifs en GM et PT n est plus systématique, mais peut encore exister selon le laboratoire fournisseur, en effet 1 des 3 laboratoires avait une association statistique. Elle confirme également l intérêt de teste les lots de PT in vitro. La seconde étude a porté sur les patients hospitalisés uniquement en USI sur les deux années. Nous avons étudié de façon quasi-expérimentale, l impact de l épuration de l air d une part sur l environnement et d autre part sur l incidence des AI dans l USI d hématologie du Centre Hospitalier de Versailles. En effet, la mise en place des PlasmairsTM s est divisée en deux phases, la première en 2009, et la seconde en 2011-2012. Nous avons pu, de ce fait, comparer, dans le même temps et dans le même lieu, les prélèvements environnementaux des chambres équipées et non équipées, et l incidence des AI selon les séjours en chambre équipée ou non. Pour les patients ayant été hospitalisés dans une chambre ne comportant pas de système de traitement de l air de type Plasmair , le risque de développer une aspergillose invasive est multiplié par 4,3 par comparaison avec les patients protégés (p=0,03). Nos données apportent un argumentaire très important en faveur de l efficacité et de l importance des mesures environnementales sur la contamination aérienne fungique et surtout pour la première fois à notre connaissance en dehors du contexte de la greffe de moelle osseuse, démontrent que ces mesures ont un impact direct sur le risque pour les patients aplasiques de développer une aspergillose invasiveInvasive aspergillosis (IA) is an opportunistic disease associated with a high death rate in patients with hemtological malignancy. Early diagnosis influences the therapeutic strategy and the prognosis. Two studies were conducted at the Centre Hospitalier de Versailles in 2009 and 2010. The first investigated the diagnostic value of the detection of galactomannan antigen. False postive galactomannan are known to be associated with the administration of piperacillin-tazobactam (PT), the main antibiotic used in hemtology. We tested all patients, in aplasia, hospitalized in the unit. Our results suggest that the association between a false positive GM and PT administration is not a systematic finding, but can be related to the laboratory supplier. This observation confirms the need to test the batches of PT in vitro before their use in the clinic. The second study conducted during a two years period and focused on patients hospitalized in the ICU. We had the opportunity to compare, during the same period of time and in the same unit, the impact of air purification on the contamination of the patient's room and the relationship between air purification and the incidence of AI. Patients hospitalized in a room having no system of air-purification (plasmair TM), had a relative the risk of developing invasive as high as 4.3 compared with protecte patient (p=0.03). Our study demonstrated the effectiveness of environmental measures on the fungal contamination of air in an hematologic ICU outside the bone marrow transplant setting Moreover, we established that these measures had a direct impact on the risk of developing invasive aspergillosis in neutropenic patientsST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Impact of medical and pharmaceutical interventions on anti-infective prescriptions: an observational study

International audienceAppropriate prescribing of anti-infectives is a public health challenge. In our hospital, clinical microbiologists (clinical microbiology mobile unit, UMMc) and clinical pharmacists (clinical pharmacy, PHAc) carry out interventions on anti-infective prescriptions to improve practices. Our main objective was to evaluate the acceptance of UMMc and PHAc interventions on anti-infective prescriptions by quantifying the rate of prescription change 24 h after intervention. The secondary objective was to characterize the type of intervention and associate the rate of change for each. All prescriptions are computerized, and interventions traced via DxCare® software, which feeds a local data warehouse (HEGP-CDW). This descriptive, retrospective, single-center, uncontrolled study was conducted from January 2015 to December 2018. The data were extracted over this period from the data warehouse and analyzed using R software. UMMc interventions were accepted 72.2% of the time and PHA interventions 87.3%. The types of interventions found were mostly dose adjustments (61.1% for the UMMc and 54.2% for the PHAc) and proposals to change or stop a drug. Interventions have an impact on anti-infective prescriptions and are generally followed by clinicians. For the category “discontinuation of a molecule”, almost half of the advice from the UMMc was refused. The collaboration between the UMMc and PHAc should be reinforced to improve acceptance

Influence of Renal Function and Age on the Pharmacokinetics of Levofloxacin in Patients with Bone and Joint Infections

Despite its efficacy and toxicity being exposure-related, levofloxacin pharmacokinetics in patients with bone and joint infections has been poorly described to date, so the possible need for a dose adjustment is unknown in this population. A prospective population pharmacokinetic study was conducted in 59 patients to answer this question. The final model consisted of a one-compartment model with first-order absorption and elimination. Mean parameter estimates (% interindividual variability) were 0.895 h−1 for the absorption rate constant (Ka), 6.10 L/h (40%) for the apparent clearance (CL/F), 90.6 L (25%) for the apparent distribution volume (V/F). Age and glomerular filtration rate (GFR), estimated by the modification of diet in renal disease formula, were related to CL/F by power models, and CL/F was found to increase for increasing GFR and decreasing age. For a similar GFR, the simulated area under the curve (AUC) was 55% higher in 70 years-old patients compared to 30 year-old patients. Based on this model, a 750 mg dose should provide an optimal exposure (AUC/ minimum inhibitory concentration (MIC) ≥100), with the possible exception of patients older than 60 years and with GFR <70 mL/min/m² who may necessitate a dose reduction, and patients with infections caused by bacteria with MIC close to 1 mg/L who may need an increase in the dose

Additional file 1 of Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal post-surgical spinal infections: a retrospective observational study

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Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils

International audienceAbstract The human pathogen Neisseria meningitidis can cause meningitis and fatal systemic disease. The bacteria colonize blood vessels and rapidly cause vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, we use a humanized mouse model to show that vascular colonization leads to the recruitment of neutrophils, which partially reduce bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles, adhesion molecules such as E-Selectin are not expressed on the endothelium, and intravascular neutrophil recruitment is minimal. Our results indicate that the colonization of capillaries and arterioles by N. meningitidis creates an intravascular niche that precludes the action of neutrophils, resulting in immune escape and progression of the infection

Incidence, risk factors and prediction of post-operative acute kidney injury following cardiac surgery for active infective endocarditis: an observational study.

International audienceINTRODUCTION: Cardiac surgery is frequently needed in patients with infective endocarditis (IE). Acute kidney injury (AKI) often complicates IE and is associated with poor outcomes. The purpose of the study was to determine the risk factors for post-operative AKI in patients operated on for IE. METHODS: A retrospective, non-interventional study of prospectively collected data (2000-2010) included patients with IE and cardiac surgery with cardio-pulmonary bypass. The primary outcome was post-operative AKI, defined as the development of AKI or progression of AKI based on the acute kidney injury network (AKIN) definition. We used ensemble machine learning ("Super Learning") to develop a predictor of AKI based on potential risk factors, and evaluated its performance using V-fold cross validation. We identified clinically important predictors among a set of risk factors using Targeted Maximum Likelihood Estimation. RESULTS: 202 patients were included, of which 120 (59%) experienced a post-operative AKI. 65 (32.2%) patients presented an AKI before surgery while 91 (45%) presented a progression of AKI in the post-operative period. 20 patients (9.9%) required a renal replacement therapy during the post-operative ICU stay and 30 (14.8%) died during their hospital stay. The following variables were found to be significantly associated with renal function impairment, after adjustment for other risk factors: multiple surgery (OR: 4.16, 95% CI: 2.98-5.80, p<0.001), pre-operative anemia (OR: 1.89, 95% CI: 1.34-2.66, p<0.001), transfusion requirement during surgery (OR: 2.38, 95% CI: 1.55-3.63, p<0.001), and the use of vancomycin (OR: 2.63, 95% CI: 2.07-3.34, p<0.001), aminoglycosides (OR: 1.44, 95% CI: 1.13-1.83, p=0.004) or contrast iodine (OR: 1.70, 95% CI: 1.37-2.12, p<0.001). Post-operative but not pre-operative AKI was associated with hospital mortality. CONCLUSIONS: Post-operative AKI following cardiopulmonary bypass for IE results from additive hits to the kidney. We identified several potentially modifiable risk factors such as treatment with vancomycin or aminoglycosides or pre-operative anemia

Comparison Between ESC and Duke Criteria for the Diagnosis of Prosthetic Valve Infective Endocarditis

International audienceObjectives: The primary objective was to assess the value of the European Society of Cardiology (ESC) criteria, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in prosthetic valve infective endocarditis (PVE). Secondary objectives were: 1) to assess the reproducibility of 18F-FDG-PET/CT; 2) to compare its diagnostic value with that of echocardiography; and 3) to assess the diagnostic value of the presence of a diffuse splenic uptake BACKGROUND: 18F-FDG PET/CT has been added as a major criterion in the ESC 2015 infective endocarditis (IE) guidelines, but the benefit of the ESC criteria has not been prospectively compared with the conventional Duke criteria.Methods: Between 2014 and 2017, 175 patients with suspected PVE were prospectively included in 3 French centers. After exclusion of patients with uninterpretable 18F-FDG PET/CT, 115 patients were evaluated, including 91 definite and 24 rejected IE, as defined by an expert consensus.Results: Cardiac uptake by 18F-FDG PET/CT was observed in 67 of 91 patients with definite PVE and 6 with rejected IE (sensitivity 73.6% [95% confidence interval (CI): 63.3% to 82.3%], specificity 75% [95% CI: 53.3% to 90.2%]). The ESC 2015 classification increased the sensitivity of Duke criteria from 57.1% (95% CI: 46.3% to 67.5%) to 83.5% (95% CI: 74.3% to 90.5%) (p < 0.001), but decreased its specificity from 95.8% (95% CI: 78.9% to 99.9%) to 70.8% (95% CI: 48.9% to 87.4%). Intraobserver reproducibility of 18F-FDG PET/CT was good (kappa = 0.84) but interobserver reproducibility was less satisfactory (kappa = 0.63). A diffuse splenic uptake was observed in 24 (20.3%) patients, including 23 (25.3%) of definite PVE, and only 1 (4.2%) rejected PVE (p = 0.024).Conclusions: 18F-FDG PET/CT is a useful diagnostic tool in suspected PVE, and explains the greater sensitivity of ESC criteria than Duke criteria. However, 18F-FDG PET/CT also presents with important limitations concerning its feasibility, specificity, and reproducibility. Our study describes for the first time a new endocarditis criterion, that is, the presence of a diffuse splenic uptake on 18F-FDG PET/CT