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Resume Le PTT auto-immun (PTTi) est une maladie rare presque constamment fatale en l’absence de traitement. Sa physiopathologie repose sur un deficit fonctionnel severe de la metalloprotease ADAMTS13 (activite

Age-related physiological changes, particularly immune system decline, may contribute to greater vulnerability to infectious diseases in older individuals. A growing body of evidence shows that both, acute, and chronic infections may be accompanied by cognitive disturbances as part of their manifestations. Given the importance of cognition in aging trajectories, the objective of this article was to review current knowledge on cognitive outcomes of infectious diseases in older adults, and to emphasize the importance of considering cognition as a domain of interest in its own rights in these diseases.A MEDLINE/PubMed database search was conducted to identify articles reporting cognitive impairment associated with various severe acute infections and specific chronic infectious conditions such as human immune deficiency virus, the herpes virus family, hepatitis C virus, Lyme borreliosis, Helicobacter pylori, periodontitis, and emerging pathogens like SARS-CoV-2, as well as potentially preventive strategies like vaccination.Taken together, the studies examined in the present review emphasize that numerous acute and chronic infectious diseases share mechanisms that, when added to specific risk factors frequently found in older persons, contribute to considerably increase the risk of cognitive outcomes such as cognitive decline and dementia. This review may help to appreciate the role that infectious diseases play in cognitive trajectories and thus promote further investigation on the topic.

Background There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD). Methods By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS. Results A single PAT course early-in-life exacerbated later DSS-induced colitis by both perturbing the microbial community and altering mucosal immune cell composition. By conventionalizing germ-free mice with either antibiotic-perturbed or control microbiota obtained 40 days after the challenge ended, we showed the transferrable and direct effect of the still-perturbed microbiota on colitis severity in the DSS model. Conclusions The findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.

Several studies have already explored individual and environmental risk factors for COVID-19 morality, however most study populations consisted of the overall population and mainly from China or the US. Our study focused on COVID-19 mortality in the elderly in seven European cities. Long-term exposure to air pollution was estimated through annual pollutant concentrations at the residential address averaged over the last two years of the study period between February and May 2020. We focused on the main outdoor air pollutants PM10, PM2.5, NO2 and O3. Short-term variations in air pollutants and weather parameters (e.g. temperature, UV, relative humidity) were also examined through a 20-day period before the confirmed PCR diagnostic of COVID-19. Individual risk factors such as smoking status, sex, body mass index (BMI), ischemic heart disease, diabetes, hypertension, chronic renal failure, history of cancer, COPD, and lung fibrosis, were taken into account. We found positive associations for diabetes and COVID-19 mortality (OR 2.2 CI 95% :1.1, 4.4). Using a multivariate logistic regression model adjusted for all patient characteristics and city, we fail to reject the null hypothesis of no association between COVID-19 mortality and long-term and short-term increase in PM2.5, PM10, NO2 and O3. Our study suffers from the fact that patient profiles strongly differ between high-polluted and less-polluted cities. Strong differences in COVID-19 mortalities were observed between cities, which could be due to differences in COVID-19 management and treatment, such as accessibility to reanimation and intensive units between cities. Overall, our study highlights the need to improve estimation of individual exposure to air pollution. Indeed, even with the high-efficiency modelisation systems used in our study, we were unable to estimate the effect of air pollution within each city, because variations in air pollution exposure were too small. Individual markers of air pollution exposure such as recently demonstrated with urinary black carbon or passive individual samplers, would be most suitable for future explorations. Concerning weather parameters, although previous studies concluded that increase in temperature and UV index could decrease COVID-19 morality, our data did not allow us to reject the null hypotheses.

BackgroundVitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Methods and findingsThis multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy 800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99],P= 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86],P= 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36],P= 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study.ConclusionsIn this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days.Trial registrationClinicalTrials.govNCT04344041.

Since the 1970s, outpatient parenteral antimicrobial therapy (OPAT) has been a viable option for patients who require intravenous antibiotics when hospitalization is not warranted. While the benefits of OPAT as a measure to improve the efficiency of healthcare delivery (i.e., reduced hospital days) and patient satisfaction are well-documented, OPAT is associated with a number of challenges, including line complications and reliance on daily healthcare interactions in some cases at home or in a clinic. To minimize the continued need for intensive healthcare services in the outpatient setting, there is trend toward patients self-administering antibiotics at home without the presence of healthcare workers, after adequate training. In most cases, patients administer the antibiotics through an established intravenous catheter. While this OPAT practice is becoming more accepted as a standard of care, the potential for line complications still exists. Outpatient subcutaneous antimicrobial therapy (OSCAT) has become an increasingly accepted alternative route of administration of antibiotics to IV by French infectious diseases physicians and geriatricians; however, currently, no antibiotics are approved to be administered subcutaneously. Antibiotics with longer half-lives that are completely absorbed and have a favorable local tolerability profile are ideal candidates for OSCAT and have the potential to maximize the quality and efficiency of parenteral antibiotic delivery in the outpatient setting. The increasing development of wearable, on-body subcutaneous delivery systems make OSCAT even more viable as they increase patient independence while avoiding line complications and potentially removing the need for direct healthcare professional observation.

Introduction En France, l’administration d’antibiotiques (ATB) par voie sous-cutanee (SC) est une pratique frequente en milieu hospitalier. Ses avantages (simplicite d’utilisation, effets indesirables rares et benins) lui conferent egalement un interet potentiel en medecine ambulatoire. Cependant, il n’existe aucune donnee disponible sur les modalites de recours a cette pratique par les medecins generalistes (MG). Materiels et methodes Enquete en ligne, realisee sur la base du volontariat, entre le 1/12/2020 et le 18/01/2021 aupres des MG de 36 departements francais. Resultats Au total, 369 MG ont participe (54 % d’âge Conclusion La voie SC pour administrer des ATB en medecine ambulatoire parait utile et plus de la moitie des MG y ont recours. Des etudes pharmacocinetiques complementaires sont donc indispensables pour valider l’utilisation de cette voie. Une meilleure formation des MG est egalement necessaire pour mieux encadrer cette pratique realisee hors AMM.

International audience; No abstract available

Depression symptoms and lower health-related quality of life (HRQoL) are associated with inflammation. This multicenter dietary intervention was shown to reduce inflammation in older people. This was the main outcome. Here, we describe the effects on HRQoL, anxiety, and depressive symptoms according to inflammation status. Overall, 125 healthy older subjects (65−80 year) were recruited (Italy, France, and Germany) and randomized into four arms (A, Healthy diet (HD); B, HD plus De Simone Formulation probiotic blend; C, HD plus AISA d-Limonene; D, HD plus Argan oil). The HD was weight maintaining, rich in antioxidant vitamins, polyphenols, polyunsaturated fatty acids (n6: n3 ratio = 3:1), and fiber. Data on inflammatory parameters, mental (MCS) and physical (PCS) component summaries of HRQoL (SF−36), anxiety symptoms (STAI state), and depressive symptoms (CES-D) were collected before and after 56 days of intervention. Body fat mass proportion (BFM) was considered a co-variable. A decrease of CES-D score was seen in the four arms (A: −40.0%, p = 0.001; B: −32.5%, p = 0.023; C: −42.8%, p = 0.004; and D: −33.3%, p = 0.21). Within the subgroups of subjects with medium/high inflammation a similar decrease in CES-D score occurred in all groups (A: −44.8%, p = 0.021; B, −46.7%, p = 0.024; C, −52.2%, p = 0.039; D, −43.8%, p = 0.037). The effect of interventions on CES-D was not related to baseline inflammation. MCS-HRQoL improved in A and C. There was no change in anxiety or PCS-HRQoL. In this trial with no control group, a decrease in depressive symptoms in healthy older volunteers was observed after a 2-month healthy diet intervention, independently of inflammation but with possible limitations due to participation.

Objectives To assess the 30-day mortality predictive markers in the oldest patients with Clostridioides difficile infection (CDI) and to analyze the accuracy of the European severity risk markers in this population. Design Observational prospective multicenter cohort study conducted by the French Infectious Diseases Society and Geriatrics Society networks. An electronic questionnaire was sent to members of both societies regarding their participation. Each investigator used an online survey to gather the data. Setting and participants Patients aged ≥75 years hospitalized in French geriatric or infectious wards with confirmed diagnosis of CDI between March 1, 2016 and May 1, 2017. Methods Clinical and laboratory parameters included medical history and comorbidities with the Cumulative Illness Rating Scale (CIRS). Criteria increasing the risk of severe disease were recorded as listed in the European guidelines. Therapeutic management, recurrence, and mortality rates were assessed at day 30 after diagnosis. Results Included patients numbered 247; mean age was 87.2 years (SD 5.4). Most of the CDI incidences (66.4%) were health care–associated infections, with 81% diagnosed within 30 days of hospitalization; CIRS mean score was 16.6 (SD 6.6). Markers of severity ≥3 included 97 patients (39.3%). Metronidazole was the main initial treatment (51.0%). C difficile infection in the older adult was associated with a 30-day mortality of 12.6%. Multivariate analysis showed that baseline CIRS score [hazard ratio (HR) 1.06 per 1-point increase, 95% confidence interval (CI) 1.00-1.12] and evidence of cardiac, respiratory, or renal decompensation (HR 3.04, 95% CI 1.40-6.59) were significantly associated with mortality. Conclusions and implications European severity markers are adequate in the oldest old. Organ failure and comorbidities appeared to be the main markers of prognosis, and these should raise the awareness of practitioners. Although antibiotic treatment was not predictive of mortality, our results point out the lack of adherence to current guidelines in this population.

International audience; Despite extensive research, the origin of Alzheimer's disease (AD) remains unknown. The role of infectious pathogens has recently emerged. Epidemiological studies have shown that Helicobacter pylori infection increases the risk of developing AD. We hypothesized that H. pylon-induced gastritis may be associated with a systemic inflammation and finally neuroinflammation. C57BL/6 mice were infected with H. pylori (n= 15) or Helicobacter felis (n= 13) or left uninfected (n = 9) during 18 months. Gastritis, amyloid deposition, astroglial and microglial cell area, and systemic and brain cytokines were assessed. The infection (H. felis>H. pylori) induced a severe gastritis and an increased neuroinflammation but without brain amyloid deposition or systemic inflammation.

Summary Introduction Malnutrition and nutrition-related diseases are associated with hospital admissions, disability, institutionalization, and mortality in older people. Specialists in Geriatric Medicine and nutrition evaluate nutritional status as part of the comprehensive geriatric assessment; however, malnutrition still remains under-recognized and under-managed. Our survey explored nutrition assessment approaches used in daily clinical practice by geriatricians across Europe. Methods A 19-item survey on methods and instruments for malnutrition assessment in geriatric settings, and details of any national guidelines, was sent to 40 postgraduate fellows of the European Academy of Medicine of Aging (EAMA, 2017–2019 class). Results Thirty-six of the 40 eligible EAMA participants, representing 14 European countries, responded. In clinical practice, MNA and MNA-SF were most frequently used for screening (44.1%, 52.9%, respectively) and diagnosing (45.7%, 40.0%) malnutrition. Weight loss (n = 36, 100%), body mass index (n = 30, 85.7%), and low energy/food intake (n = 27, 77.1%) were the most frequent clinical variables considered. The absolute and relative amount of weight loss, and over what time period, varied widely. These routinely considered clinical factors contribute to validated GLIM, ASPEN-AND and ESPEN criteria for diagnosis of malnutrition, but these criteria were seldom used (GLIM = 0%, ASPEN = 0%; n = 9, ESPEN = 25.7%). National guidelines were available in 9 of the 14 countries, and generally recommended MNA and MNA-SF for community-dwelling and hospitalized older patients. Albumin was often suggested as a nutritional marker. Conclusions Nutritional assessment is systematically performed in geriatrics; but differs widely among geriatricians and countries. Harmonizing guidelines with the new international consensus might provide best-evidence care for older people across Europe.

IMPORTANCE: Exposure to Borrelia burgdorferi (Bb) has been reported to be associated with certain neuropsychiatric disorders. OBJECTIVE: To establish the association between seropositivity to Bb and incidental neuropsychiatric disorders (eg, cognitive decline, incident dementia, and depressive symptoms) as well as functional decline. DESIGN, SETTING, AND PARTICIPANTS: This prospective, 6-year follow-up cohort study was conducted in a rural southwestern region of France and included 689 retired farmers 65 years or older randomly recruited from the Farmer Health Insurance System who agreed to submit a blood sample and were participants in the Aging Multidisciplinary Investigation study, an ongoing epidemiological prospective study of aging initiated in 2007. The data were analyzed from April to May 2019. EXPOSURES: Borrelia burgdorferi serology testing was performed in a 2-tiered approach. During the follow-up period, cognitive decline, incident dementia, depressive symptoms, and functional decline were repeatedly assessed. MAIN OUTCOMES AND MEASURES: Diagnosis of dementia relied on a 3-step procedure; cognitive decline was determined using the Mini-Mental State Examination and depressive symptomatology was assessed using the Center for Epidemiologic Studies Depression scale. For disability, scores on instrumental and basic activities of daily living were investigated. RESULTS: Of 689 participants, 432 (62.2%) were men and the mean (SD) age was 75.8 (6.4) years. The seroprevalence rate of Bb was 6.5%. At baseline, compared with Bb− participants, those who were Bb+ were older, predominantly men, and had lower depressive symptoms. No association between seropositivity and any of the studied outcomes (ie, cognitive decline, depressive symptoms, or functional decline) was found in the crude analysis and after adjusting for confounding variables. Regarding incident dementia, no increased risk was found among Bb+ participants (hazard ratio, 0.42; 95% CI, 0.1-1.17; adjusted for diverse confounders). CONCLUSIONS AND RELEVANCE: To our knowledge, this is one of the few longitudinal studies exploring the risk of neuropsychiatric disorders and functional decline associated with exposure to Bb. Despite its limitations (eg, a lack of information if clinical manifestations of Lyme borreliosis existed, date of exposure, or treatment received), this study suggests that seropositivity to Bb is not a risk factor for incidental neuropsychiatric disorders and functional decline.

The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility., Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (β-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens.

Objectives To describe the rationale for subcutaneous (SC) administration of antibiotics from available published data and to make propositions to help clinicians in daily practice. Design Narrative review. Setting and Participants Hospitalized patients, persons in long-term care facilities and ambulatory care. Methods We searched the MEDLINE/PubMed electronic database for evidence supporting SC administration of antibiotics up to September 2019; the results of this primary search were supplemented by searching the references of the identified articles, as well as by searching in Google Scholar. Results Regarding tolerability, efficacy, and pharmacokinetic/pharmacodynamic profiles, most studies suggest that the SC route could be an alternative to the intravenous route, particularly for time-dependent antibiotics and among certain patient populations, such as patients with poor venous access, swallowing disorders, or behavioral disturbance. However, clinical evidence of the benefits and risks of SC antibiotic administration is still scarce and of low level. Conclusions and Implications SC administration of antibiotics may be useful in various settings such as in hospitalized patients and among those in long-term care facilities or being cared for at home. However, further clinical studies are needed to assess the pharmacokinetic/pharmacodynamic properties, as well as the risks and benefits of SC administration of antibiotics. In this review, we highlight the potential benefits of SC administration of antibiotics and address practical recommendations for its use. This information will enable improvement of treatment strategies and present the SC route as a potential option in specific situations.

Introduction Les bacteriemies a enterobacteries (EB) sont frequentes chez les sujets âges. Le choix de l’antibiotherapie probabiliste est souvent difficile. Les modalites de traitement de ces infections (nature et duree de l’antibiotherapie) sont de plus encore mal codifiees dans cette population. L’objectif de cette etude etait de decrire les modalites de prise en charge des bacteriemies a EB du patient âge et de determiner la proportion d’antibiotherapie probabiliste efficace. Materiels et methodes Etude multicentrique retrospective. Chaque investigateur a inclus les 10 derniers patients > 75 ans pris en charge dans leur service (MCO, SSR, USLD ou EHPAD) pour une bacteriemie a EB. Des donnees cliniques, microbiologiques, therapeutique et pronostiques ont ete collectees. Resultats Quarante-sept centres en France et en Belgique (23 CH et 24 CHU) ont inclus 504 patients (87 ± 6 ans, 50 % d’hommes) vivant majoritairement au domicile (428, 85 %) et polypathologique (Charlson moyen 3,8 ± 1,8). La plupart des hemocultures ont ete prelevees en MCO (409 [180 geriatrie, 32 maladies infectieuses et 147 urgences]). Dix-sept pour cent (84/502) avaient une temperature 2 chez 94/457 (20 %) des patients. Escherichia coli (352, 69 %), Klebsiella pneumoniae (59, 11,5 %) et Enterobacter cloacae (23, 4,5 %) etaient les plus frequents. La resistance aux C3G, aux cotrimoxazole et aux fluoroquinolones concernait respectivement 14 % (75/504), 25 % (120/487) et 17 % (85/492) des souches. L’antibiotherapie probabiliste debutee dans les 24 heures apres le prelevement de la 1re hemoculture (448/504) etait efficace sur la souche ulterieurement identifiee dans 84 % des cas (378/448). Les antibiotiques les plus souvent prescrits en premiere intention etaient la ceftriaxone (230, 45 %), la cefotaxime (96, 19 %), la piperacilline–tazobactam (61, 12 %) et l’amoxicilline–acide clavulanique (60, 12 %). Les carbapenemes prescrites en probabiliste concernaient 14 patients ; 127 (25 %) patients ont recu une bitherapie (aminosides 59 [12 %] ou metronidazole 7 [7 %]). La voie sous-cutanee etait utilisee dans 10 % des cas. La mortalite intra hospitaliere etait de 17 % (87/504) ; 39 (7 %) patients ont ete transferes en reanimation. Au cours de l’hospitalisation, les patients ont presente une chute ou un episode confusionnel dans 9 % (44/469) et 28 % (127/457) des cas. Conclusion Des analyses complementaires sont en cours sur les modalites de traitement, leur efficacite et leur impact sur le pronostic. Une meilleure connaissance des modalites de prise en charge des bacteriemies a EB chez le patient âge va permettre de mieux cibler les actions de leur optimisation. Ces premiers resultats sont rassurants sur l’usage exceptionnel et raisonne des carbapenemes en probabiliste. Une antibiotherapie.

Introduction Les definitions explicites de prescriptions potentiellement inappropriees (PPI) de medicaments ont deja montre leur interet, particulierement en geriatrie. L’application de definitions explicites de PPI pour les antibiotiques peut etre un nouvel outil complementaire aux actions menees dans la lutte contre l’antibioresistance. Cependant, il n’existe aucun referentiel de definitions explicites specifiquement adapte aux antibiotiques. L’objectif etait de constituer une liste preliminaire de definitions explicites de PPI d’antibiotiques (PPI-atb) adaptees a la personne âgee hospitalisee dans une perspective de lutte contre l’antibioresistance. Materiels et methodes Le travail s’est deroule en 3 etapes : – une revue systematique de la litterature a ete realisee pour rechercher les definitions explicites existantes ; – une etude qualitative a reuni 28 experts infectiologues et geriatres afin de formuler de nouvelles definitions explicites concernant les personnes âgees hospitalisees et les problematiques actuelles d’antibioresistance ; – les definitions issues de ces deux travaux ont ete fusionnees apres traduction des definitions anglophones et regroupement des definitions similaires. Chaque etape du travail a suivi une methode en double lecture et a beneficie d’une validation par un comite de pilotage et par des groupes de travail externes. Resultats La revue systematique de la litterature a permis de relever 62 definitions explicites de PPI-atb issues de 93 articles. L’enquete qualitative a permis d’identifier 65 definitions lors de 4 focus groupes, dont 56 (85 %) etaient de nouvelles definitions explicites. La fusion de ces resultats a permis d’obtenir une liste preliminaire de 103 definitions explicites de PPI-atb. Conclusion Ce travail propose un contenu important de 103 definitions explicite de PPI-atb. Toutes ne sont pas pertinentes a ce stade du fait de la nature exploratoire du travail. Cette liste preliminaire necessite d’etre soumise a une enquete Delphi ou un panel d’experts retiendra les definitions explicites de PPI-atb qui pourraient etre utilisees dans des programmes de bon usage des antibiotiques.

In the last year, many studies have demonstrated a potential role of Helicobacter pylori in the pathogenic mechanisms of different extragastric diseases. While the role of H pylori in idiopathic thrombocytopenic purpura, idiopathic iron deficiency anemia, and vitamin B12 deficiency has already been demonstrated, there is growing evidence of other related conditions, especially cardiovascular, metabolic, and neurologic disorders, including neurodegenerative diseases. A summary of the results of the most relevant studies published over the last year on this attractive topic is presented in this review.

Managing infective endocarditis in older patients is of growing concern since this severe infection is increasingly frequent in this population and is responsible for high mortality and morbidity. Specific issues concerning diagnostic procedures, antibiotic therapy and cardiac surgical decisions in this patient setting are highlighted here. They indicate that infectious diseases physicians, cardiologists and cardiac surgeons should adapt their therapeutic strategy beyond the available guidelines. Recent data also showed that geriatric parameters, such as functional and nutritional status, are crucial components impacted by infective endocarditis and related to a worse outcome in older patients. Geriatricians are expert in evaluating older patients, and detecting and managing these problems. We discuss here why we consider that geriatricians should be involved in the management of these patients.

In older patients, the agreement is low between creatinine clearance estimated with the Cockcroft-Gault equation (eCrCl) and glomerular filtration rate estimated with the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI). The implications of these discrepancies for drug prescription have so far been assessed only for a few selected molecules. The aim of this study was to investigate the proportion of geriatric patients receiving drugs with a different recommended dose or indication (i.e. an adjustment discrepancy) depending on eCrCl versus eGFRCKD-EPI estimates of kidney function. Patients admitted to acute geriatric care units in our university hospital were eligible for inclusion. All drug classes were studied. We retrospectively determined recommended prescriptions according to eCrCl and eGFRCKD-EPI. Sixty percent of patients received at least one drug requiring dose adjustment and/or received a drug with a relative contraindication based on their estimated kidney function. Thirty-one percent of patients received at least one drug with an adjustment discrepancy: 20% received at least one drug for which the recommended dose differed depending on eCrCl versus eGFRCKD-EPI estimates of kidney function, 4% received a drug with a relative contraindication according to eCrCl but not eGFRCKD-EPI, and 7% received both. Factors independently associated with an adjustment discrepancy were older age and lower weight. Main drug classes involved were benzodiazepines, anticoagulants, and anti-microbial drugs. In acute geriatric care units, recommended drug dose adjustments are frequently discordant according to the equations used to estimate kidney function, notably for benzodiazepines, anticoagulants, and anti-microbial drugs. The consequences for treatment efficacy and safety should be investigated.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (/=60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 x 103/mm3 [9-57] vs 13 x 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age >/=60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.

BACKGROUND: The absence of fever in bacteremia in patients who are older is known to delay diagnosis. Our objective was to determine whether atypical presentation was associated to mortality as a result of bacteremia in this patient cohort as well as possible factors associated with this atypical presentation. METHODS: We conducted an observational prospective study in 2 French university hospitals in 2016-2017 including patients ages >/=75 years with bacteremia. Atypical presentation was defined as the absence of a temperature >/=38.3 degrees C or

Background Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria. Objectives To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons. Methods Patients >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0–24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386. Results Ten (mean ± SD age=87±7 years) and 16 (age=88±5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12±5.9 versus 12±7.4 mg/L, P=0.97; C2.5=97±42 versus 67±41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=184±90 versus 51±66 mg/L, P=0.001). The mean individual AUCs (1126.92±334.99 mg·h/L for IV versus 1005.3±266.0 mg·h/L for SC, P=0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted. Conclusions SC administration of ertapenem is an alternative to IV administration in older patients.

International audience; Alzheimer's disease (AD) is associated with Aß peptide and Tau protein deposits, but the initial process inducing the disease and ultimately neurodegeneration has not yet been elucidated. An infectious hypothesis is suggested by the alteration of the blood-brain barrier and the activation of neuroinflammation in the brain, which could play a role, especially in the decrease of Aß peptide clearance. Several viral or bacterial agents have been incriminated, including Helicobacter pylori. Infection by H. pylori is acquired during childhood and often lifetime persisting, inducing a chronic gastric inflammation, which remains asymptomatic in approximately 80% of cases. However H. pylori infection can induce systemic inflammation and increase homocysteine levels, contributing to worsen AD lesions. Association between H. pylori and AD is suggested by 1) epidemiologic studies, which show higher AD prevalence and more pronounced cognitive impairment in infected than in non-infected subjects; 2) experimental studies in murine models: a) in a first study we evaluated the impact of H. pylori infection on the brain of non-AD predisposed C57BL/6J mice. After an 18-month infection, H. pylori induced a significant gastric inflammation but no brain Aβ deposit nor increased neuroinflammation was observed in their brain; b) we currently study the impact of Helicobacter species infection on behavior and cerebral lesions of AD transgenic (APPswe/PS1dE9) mice and their wild type littermate. The results of these studies do not allow to conclude a significant association between AD and H. pylory infection but may contribute to a better understanding of the role of brain neuroinflammation in AD.

International audience; Background/ Objective:Although poorly documented, subcutaneous (SC) administration of antibiotics is common practice in France especially in Geriatrics Departments. The aim of this study was to determine the tolerance of such a practice.Design:Prospective observational multicentre study.Methods:Sixty-six physicians accepted to participate from 50 French Infectious Diseases and Geriatrics Departments. From May to September 2014, patients treated at least one day with SC antibiotics could be included. Modalities of subcutaneous administration, occurrence of local and systemic adverse effects (AE) and clinical course were collected until the end of the treatment.Results:Two hundred-nineteen patients (83.0 [19–104] yo) were included. Ceftriaxone (n = 163, 74.4%), and ertapenem (n = 30, 13.7%) were the most often prescribed antibiotics. The SC route was mainly used because of poor venous access (65.3%) and/or palliative care (32.4%). Fifty patients (22.8%) experienced at least one local AE that led to an increased hospital stay for two patients (4.0%) and a discontinuation of the SC infusion in six patients (12.0%). A binary logistic regression for multivariate analysis identified the class of antibiotic (p = 0.002) especially teicoplanin and the use of rigid catheter (p = 0.009) as factors independently associated with AE. In over 80% of cases, SC antibiotics were well tolerated and associated with clinical recovery.Conclusions:SC administration of antibiotics leads to frequent but local and mild AE. Use of non-rigid catheter appears to be protective against AE. As it appears to be a safe alternative to the intravenous route, more studies are needed regarding efficacy and pharmacokinetics.

Introduction Le purpura thrombotique thrombocytopenique (PTT) acquis est une microangiopathie thrombotique (MAT) associant une anemie hemolytique mecanique, une thrombopenie et des defaillances d’organes. Son diagnostic est confirme par un deficit severe en ADAMTS13 associe a des anticorps anti-ADAMTS13. Le PTT est fatal en l’absence d’un traitement associant echanges plasmatiques quotidiens, corticoides et rituximab. L’âge et le vieillissement cardiovasculaire semblent impliques dans le pronostic du PTT mais les caracteristiques du PTT chez le sujet âge restent encore mal connues. Patients et methodes Une etude retrospective a compare les cas de PTT declares au CNR MAT d’octobre 2000 a aout 2017 en fonction de leur âge (> ou Resultats Au total, 49 patients de plus de 60 ans (âge : 72 ans ; extremes 65–95, sex-ratio homme/femme : 0,53) et 340 de moins de 60 ans (âge : 38 ans ; extremes 16–59, sex-ratio H/F : 0,38) ont ete inclus. Les sujets âges avaient plus de facteurs de risque cardiovasculaires que les sujets jeunes (avec respectivement diabete : 10 (20 %) vs 13 (83 %), p = 0,0001, cardiopathie ischemique : 8 (16 %) vs 8 (2 %), p = 0,0002, dyslipidemie : 22 (46 %) vs 31 (9 %), p Conclusion Le PTT a une presentation neurologique atypique chez le sujet âge, marquee par une confusion et des troubles du comportement retardant probablement le diagnostic. Les atteintes cardiaques et renales sont plus frequentes chez les sujets âges, dont le terrain vasculaire est plus marque, les cytopenies sont moins profondes. Le traitement initial n’est pas modifie par l’âge mais certaines difficultes de prise en charge sont specifiques aux sujets âges comme l’abord vasculaire necessitant d’envisager des traitements alternatifs comme la ciclosporine per os. L’âge > 60 ans et la presence d’une atteinte cardiaque grevent le pronostic. L’augmentation de la mortalite entre j28 et 1 an chez le sujet âge, particulierement apres 70 ans, souligne l’attention a porter aux decompensations secondaires de comorbidites apres le traitement de l’episode de PTT.

Objectives: To determine whether Helicobacter pylori infection was associated with dementia and risk of developing dementia in a longitudinal population-based cohort of elderly adults living in the community. Design: Prospective community-based cohort study. Setting: The population-based Personnes Agees QUID (PAQUID) Study. Participants: Six hundred three noninstitutionalized individuals aged 65 and older living in the southwest of France followed from 1989 to 2008. Measurements: A descriptive and comparative analysis including dementia prevalence, according to H. pylori status (serology), was made at baseline. Cox proportional hazard models were used to study the risk of developing dementia according to H. pylori status assessed on sera samples from elderly adults initially free of dementia and followed for 20 years. A neurologist diagnosed dementia according to Diagnostic and Statistical Manual of Mental Disorders Third Edition criteria. Results: At baseline, 391 (64.8%) subjects (348 women, mean age 73.9 ± 6.5) were seropositive for H. pylori. Dementia prevalence was higher in the infected group (5.4% vs 1.4%, P = .02). After 20 years of follow-up, 148 incident cases of dementia were diagnosed. After controlling for age, sex, educational level, apolipoprotein E4 status, cardiovascular risk factors, and Mini-Mental State Examination score, H. pylori infection was determined to be a risk factor for developing dementia (hazard ratio = 1.46, P = .04). Conclusion: This longitudinal population-based study provides additional epidemiological support to the hypothesis of an association between dementia and H. pylori infection, which may enhance neurodegeneration.

Emmanuel Forestier,1 Thibaut Fraisse,2 Claire Roubaud-Baudron,3 Christine Selton-Suty,4 Leonardo Pagani5 1Infectious Diseases Department, Centre Hospitalier Métropole Savoie, Chambéry, France; 2Acute Geriatric Department, Centre Hospitalier, Alès, France; 3Geriatric Department, University Hospital, Bordeaux, France; 4Department of Cardiology, University Hospital, Nancy, France; 5Infectious Diseases Department, Centre Hospitalier Annecy-Genevois, Annecy, France Abstract: The incidence of infective endocarditis (IE) rises in industrialized countries. Older people are more affected by this severe disease, notably because of the increasing number of invasive procedures and intracardiac devices implanted in these patients. Peculiar clinical and echocardiographic features, microorganisms involved, and prognosis of IE in elderly have been underlined in several studies. Additionally, elderly population appears quite heterogeneous, from healthy people without past medical history to patients with multiple diseases or who are even bedridden. However, the management of IE in this population has been poorly explored, and international guidelines do not recommend adapting the therapeutic strategy to the patient’s functional status and comorbidities. Yet, if IE should be treated according to current recommendations in the healthiest patients, concerns may rise for older patients who suffer from several chronic diseases, especially renal failure, and are on polypharmacy. Treating frailest patients with high-dose intravenous antibiotics during a prolonged hospital stay as recommended for younger patients could also expose them to functional decline and toxic effect. Likewise, the place of surgery according to the aging characteristics of each patient is unclear. The aim of this article is to review the recent data on epidemiology of IE and its peculiarities in the elderly. Then, its management and various therapeutic approaches that can be considered according to and beyond guidelines depending on patient comorbidities and frailty are discussed. Keywords: infective endocarditis, elderly, antibiotic therapy, cardiac surgery, frailty

International audience; Several hypotheses are proposed for understanding the Alzheimer's disease (AD) pathological mechanisms, mainly the amyloid theory, but the process inducing Aß peptide deposit, tau protein degeneration, and ultimately neuronal loss, is still to be elucidated. Alteration of the blood-brain barrier and activation of neuroinflammation seem to play an important role in AD neurodegeneration, especially in the decrease of Aß peptide clearance, therefore suggesting a role of infectious agents. Epidemiological and experimental studies on cellular or murine models related to herpes simplex virus (HSV), spirochetes, Chlamydia pneumoniae or Borrelia, and systemic inflammation are reviewed. Aß peptide or tau protein could also behave like a prion protein. Infectious agents could thus have an impact on AD by direct interaction with neurotropism or systemic inflammation. Although the results of these studies are not conclusive, they may contribute to the understanding of AD pathology.

Introduction Un tiers des EI survient chez des patients de plus de 70 ans. L’objectif de notre etude a ete de decrire les caracteristiques des sujets âges atteints d’EI, en se focalisant sur leurs donnees geriatriques (autonomie, etats cognitif et nutritionnel), et d’en evaluer l’impact sur la prise en charge therapeutique et la morbi-morbidite a 3 mois. Materiels et methodes Etude observationnelle prospective ayant inclus dans 14 centres francais entre le 1/3/2015 et le 1/4/2016 des patients ≥ 75 ans atteints d’EI certaine ou possible. Une evaluation geriatrique a ete realisee la premiere semaine suivant le diagnostic d’EI (critere d’exclusion si non realisee), puis 3 mois apres pour les sujets vivants. Resultats Au total, 111 patients (âge moyen 83,1 ± 5,1 ans, hommes 53,2 %) ont ete inclus. L’EI a ete certaine chez 80 patients (72,7 %), sur prothese chez 35 patients (31,5 %) (dont 5 TAVI). Staphylococcus aureus (27,9 %) et les streptocoques d’origine digestive (36 %) ont ete les bacteries les plus impliquees. Sur le plan geriatrique, 98 patients (88,3 %) vivaient a domicile et 102 (91,9 %) marchaient avant l’EI. Le score de comorbidites Cumulative Illness Rating Scale (CIRS-G) a ete de 14,1 ± 6,9 et le score de Charlson pondere a l’âge 5,7 ± 1,8. L’autonomie de ces patients etait conservee dans les activites de la vie quotidienne 2 mois avant leur hospitalisation (score Activities in Daily Living [ADL] 5,1 ± 1,7/6). Lors de la premiere evaluation geriatrique, leur etat general etait altere (OMS = 4 pour 33 patients [30 %]). Au total, 61 patients (62,2 %) n’ont pas ete capables de marcher. Le score ADL a ete 3,2 ± 2,1. Au total, 37 patients (39,8 %) ont eu un score Mini Nutrional Assessment (MNA) Soixante-huit patients (61,3 %) ont ete traite par gentamycine pour une duree moyenne de 5,6 ± 5,4 jours. La duree moyenne du traitement antibiotique a ete de 39,5 ± 22,5 jours. 22 patients (19,8 %) ont eu un relais oral des antibiotiques. Dix-huit patients (16,2 %) ont ete operes, et 18 (16,2 %) n’ont pas ete operes malgre une indication theorique. La chirurgie n’a pas ete realisee car le risque operatoire a ete juge prohibitif en raison de l’etat general du patient (11 cas, 61,1 %) et/ou de ses capacites fonctionnelles (6 cas, 33,3 %). Les patients operes avaient moins de comorbidites (CIRS-G 9,2 ± 4,3 vs 15,2 ± 7, p Vingt-neuf patients (26,1 %) sont decedes dans les 3 mois suivant le diagnostic de l’EI. Aucune donnee infectiologique ni cardiologique de l’EI n’a influence significativement la mortalite. Les parametres geriatriques associes a une surmortalite (analyse bivariee) ont ete le score OMS (RR 1,8 (1,1–3,0), p = 0,01), le score ADL a j0 (RR 0,7 (0,5–0,9), p = 0,002), et le score MNA (RR 0,9 (0,8–1,0), p = 0,006). La mortalite a 3 mois a ete superieure chez les patients non operes alors qu’il y avait une indication theorique (52,9 %, p = 0,02), par rapport aux patients operes (16,3 %), et aux non operes sans indication (24,3 %). Les 55 patients evalues a 3 mois ont recupere une bonne autonomie (ADL 4,7 ± 1,8). Au total, 43 (81,1 %) marchaient et 45 (81,8 %) etaient revenus dans leur lieu de vie habituel. Leur MMS moyen a ete de 23,8 ± 5,7. Conclusion Les donnees geriatriques influencent directement la prise en charge et l’evolution de l’EI chez le sujet âge. Une evaluation et un suivi geriatriques de ces patients sont justifies.

Introduction Le purpura thrombotique thrombo-cytopenique (PTT) est une maladie rare au pronostic reserve associant une atteinte neurologique, une thrombopenie et une anemie hemolytique. Nous rapportons ici 3 cas de PTT « geriatriques » illustrant les difficultes diagnostiques, therapeutiques et ethiques dans cette population. Observation Cas no°1 : une patiente de 87 ans est adressee pour confusion et chutes repetees. La presence d’un syndrome neurologique, d’un purpura du bras droit, d’une thrombopenie et d’une anemie hemolytique (schizocytes a 7,5 %) fait suspecter le diagnostic PTT, confirme par une activite ADAMTS 13 indetectable et la presence d’anticorps inhibiteurs IgG. Une atteinte cardiaque, cerebrale et renale est associee a ce PTT sans etiologie retrouvee. Devant l’autonomie conservee de la patiente et des comorbidites limitees, des echanges plasmatiques (EP) et une corticotherapie (1 mg/kg/j) sont debutes avec une efficacite biologique. La patiente reste confuse et agitee, les EP sont suspendus. Un traitement par ciclosporine permet une amelioration clinico-biologique et un transfert en readaptation. Cas no°2 : une patiente de 85 ans est hospitalisee pour chutes repetees. Son autonomie est conservee. Un scanner cerebral revele un hematome sous-dural aigu. Le diagnostic de PTT est fait devant une anemie hemolytique (schizocytes a 4 %) associee a une thrombopenie, une activite ADAMTS 13 indetectable et la presence d’anticorps inhibiteurs IgG presents. Des atteintes cerebrales, cardiaque et renale sont presentes. Le bilan etiologique retrouve un adenocarcinome dedifferencie colique. Malgre un traitement par EP et corticotherapie puis secondairement par rituximab, survient une degradation neurologique et cardiaque entrainant le deces de la patient. Cas no°3 : un patient de 78 ans est hospitalise pour troubles du comportement, ataxie et abasie avec une thrombopenie. Une premiere IRM cerebrale est normale. A j7 apparait brutalement un deficit du membre superieur droit avec un infarctus cerebral recent a l’IRM. Une anemie hemolytique apparait secondairement faisant suspecter un PTT, confirme par une activite ADAMTS 13 indosable. Le bilan etiologique est negatif. Une transfusion de plasma et une corticotherapie sont inefficaces, la thrombopenie s’aggrave a 4000/mm3 et le patient decede d’une hemorragie digestive. Discussion La confusion fait partie avec l’alteration de l’etat general et la chute des 3 motifs d’hospitalisation les plus frequents en geriatrie, de plus l’anemie peut apparaitre secondairement ce qui rend le diagnostic de PTT difficile. La caracterisation de l’anemie avec la recherche de reticulocytes et de schizocytes 3 jours de suite est recommandee. La prise en charge du PTT chez le sujet âge repose sur les EP et la corticotherapie a 1 mg/kg/j en urgence par analogie au traitement chez les sujets jeunes. En cas de PTT refractaire, un traitement par rituximab est entrepris. La voie d’abord necessaire pour les EP ou les perfusions de rituximab s’est s’averee etre la difficulte principale rencontree du fait de l’agitation des nos 3 patients majoree par l’introduction de forte dose de corticoides. La mise en place de contentions physiques et chimiques est tres discutable ethiquement chez nos patients dont le confort reste la priorite devant une pathologie au pronostic tres reserve. Une etude du centre national de reference menee entre 2000 et 2009 a montre que le taux de mortalite etait d’environ 10 % chez les patients de moins de 60 ans et 35 % chez les plus âges [1] . La place de la ciclosporine reste a evaluer mais pourrait representer une alternative devant l’absence de voie d’abord [2] . Ces 3 situations survenues en 18 mois dans notre service ont ete l’occasion de confirmer l’interet de discussion entre geriatres, nephrologues et reanimateurs afin de determiner la prise en charge la plus adaptee a chaque patient âge dans ce contexte de pathologie rare, peu documentee au pronostic tres reserve. Conclusion La confusion et l’anemie sont tres frequentes en geriatrie. La caracterisation de l’anemie et la recherche d’une thrombopenie sont primordiales afin d’evoquer un PTT a juste titre. Devant la necessite de traitements invasifs, le pronostic vital effroyable et l’absence de donnee sur la qualite de vie des patients survivants, la strategie therapeutique devant un PTT du sujet âge doit etre discutee de facon collegiale entre geriatres, reanimateurs et nephrologues.

Introduction Les bacteriemies constituent une infection severe du sujet âge. La presentation clinique atypique frequente de ces infections peut retarder leur diagnostic et aggraver leur pronostic. L’objectif de ce travail etait de determiner les facteurs de risque de mortalite des bacteriemies du sujet âge, et les facteurs associes a une semiologie atypique. Materiels et methodes Une etude observationnelle prospective menee de 2016 a 2017, a inclus tout patient de plus de 75 ans hospitalise en service de geriatrie, medecine ou reanimation medicale presentant une bacteriemie, caracterisee par une hemoculture positive. Une clinique atypique correspondait a l’absence de temperature ≥ 38,3 °C ou Resultats Cent trente et un patients ont ete inclus (âge moyen : 85 ± 5,6 ans, 46,6 % de femmes). La mortalite a S1 etait de 9,2 % et a M3 de 41,4 %. En analyse multivariee, a S1, l’atypie semiologique tendait a etre associee au deces [odd ratio (OR) = 3,44, intervalle de confiance 95 % (IC) (0,82-14,49), p = 0,092] et l’infection par une bacterie a Gram negatif etait protectrice [OR = 0,08, IC95 % (0,01–0,41), p = 0,003]. A M3, l’atypie semiologique [OR = 3,97, IC95 % (1,34–11,77), p = 0,013], l’infection nosocomiale [OR = 5,69, IC95 % (2,04-15,87), p = 0,001], l’insuffisance cardiaque [OR = 4,79, IC 95 % (1,87-12,28), p = 0,001] et une neoplasie evolutive [OR = 3,20, IC95 % (1,13-9,06), p = 0,029] etaient associees a la mortalite. Les patients n’avaient pas retrouve leur niveau d’autonomie initial a 3 mois (score ADL a 2,9 vs 3,6, p = 0,052). Vingt pour cent (n = 27) des patients ont presente une semiologie atypique de la bacteriemie. Le diabete et les infections a S. aureus etaient les deux facteurs de risque de cette atypie identifies dans cette etude [OR = 2,46 (1,01–5,99), p = 0,048 et OR = 3,77 (1,14–12,41), p = 0,029, respectivement]. Conclusion Cette etude confirme le mauvais pronostic vital et fonctionnel des bacteriemies du sujet âge. La semiologie atypique est associee a une surmortalite. Des hemocultures devraient etre envisagees devant une symptomatologie brutale et inexpliquee chez un patient âge, notamment diabetique. La poursuite des inclusions permettra de determiner les facteurs de risque de deces des patients de profil clinique atypique pour mettre en place des strategies de prevention.

Introduction L’utilisation de la voie sous cutanee (SC) pour l’administration d’antibiotiques est frequente en France, en particulier en geriatrie, comme alternative a la voie intraveineuse (IV). Il existe cependant tres peu de donnees PKPD dans la litterature validant une telle pratique. L’emergence des enterobacteries secretrices de β-lactamases a spectre etendu (EBLSE) rend parfois necessaire l’emploi de carbapenemes dont l’ertapeneme. L’objectif de cette etude etait de determiner les donnees PK/PD de l’ertapeneme administre par voies sous cutanee et intraveineuse dans une population de patients âges. Materiels et methodes Il s’agit d’une etude observationnelle prospective, monocentrique incluant des patients âges de plus de 75 ans traites par ertapeneme depuis au moins 48 h (etat d’equilibre) par voie IV ou SC. Les concentrations d’ertapeneme serique (H0, H + 0,5 et H + 2,5) ont ete realisee par chromatographie en phase liquide couplee a la spectrometrie de masse. Les aires sous la courbe (ASC) ont ete calculees pour chaque voie et une simulation de Monte Carlo a ete realisee (1000 sujets âges) afin de determiner l’influence de la voie d’administration sur la probabilite de maintenir la concentration libre d’ertapeneme au-dessus de la concentration minimale inhibitrice (CMI) au moins 40 % du temps. Resultats Dix patients (âge moyen 87 ± 7,0 ans) traites par voie SC et 11 patients (88 ± 5,0 ans) par voie IV ont ete inclus dans l’etude. Les concentrations residuelles moyennes (H0) n’etaient pas significativement differentes entre la voie IV (11 ± 8 ug/mL) et la voie SC (11 ± 7 ug/mL) ; en revanche les concentrations maximales a la fin de la perfusion (H + 0,5 ; 186 ± 98 ug/mL versus 29 ± 22ug/mL) 2 h apres (101 ± 34 versus 58 ± 36ug/mL) etaient superieures avec la voie IV. Les ASC n’etaient pas differentes entre les 2 voies (986 ± 302 versus 887 ± 212 ug/mL*h, p = 0,27). La probabilite de maintenir la concentration d’ertapeneme libre au dessus de la CMI au moins 40 % du temps n’etait pas significativement differente entre les voies SC et IV. Il n’y a pas eu d’effets indesirables locaux notables. Conclusion Les premiers resultats de cette etude originale de PK/PD chez le sujet âge sont en faveur d’une utilisation possible de la voie SC pour la delivrance de l’ertapeneme par voie SC en alternative a la voie IV. La simplicite d’utilisation de la voie SC pourrait permettre de raccourcir les durees d’hospitalisation voire de les eviter dans cette population.

Resume Introduction La maladie des griffes du chat est une infection due a Bartonella henselae . Sa forme clinique la plus courante est une lesion cutanee (griffure de chat) associee a une adenopathie locoregionale. Les formes disseminees sont rares et peuvent etre source de difficultes diagnostiques. Observation Nous rapportons l’observation d’une atteinte systemique a B. henselae compliquee d’osteomyelite multifocale chez une patiente de 61 ans, immunocompetente, confirmee par PCR (adenopathie). La revue de la litterature retrouve 51 cas d’atteintes osseuses (confirmees dans 14 cas par une PCR a B. henselae positive). Conclusion Les atteintes osseuses de la maladie des griffes du chat chez l’adulte sont rares mais le diagnostic doit etre evoque grâce a l’interrogatoire. Les antibiotherapies utilisees et la place du traitement chirurgical sont discutees.

Resume Methode Nous avons analyse retrospectivement les caracteristiques demographiques, cliniques, biologiques, therapeutiques et evolutives de 11 patients hospitalises pour meningite prouvee a virus herpes simplex (HSV). Resultats Parmi eux, six etaient infectes par le VIH, quatre rapportaient un antecedent d’herpes genital et un des episodes meninges recurrents. Un debut brutal avec cephalees febriles etait note chez tous les patients et 9/11 avaient un syndrome meninge franc ; deux patients avaient des lesions anales herpetiques. L’analyse du liquide cephalorachidien (LCR) retrouvait dans tous les cas une hypercellularite a predominance lymphocytaire, une hyperproteinorachie moderee et une normoglycorachie. HSV a ete detecte dans le LCR de tous les patients par polymerase chain reaction (PCR). Le typage realise chez six patients etait positif dans tous les cas pour le virus herpes simplex de type 2 (HSV-2). Un traitement par acyclovir (ACV) intraveineux a ete debute chez 10/11 patients (extremes : trois a dix jours), avec relais par valaciclovir (VACV) (extremes : cinq a sept jours) ; un patient a ete traite par ACV per os dix jours. Dans tous les cas une remission complete des signes cliniques a ete observee en moins de 48 heures. Deux patients ont presente une meningite recurrente a HSV-2 dans les deux mois suivants, d’evolution favorable sous ACV intraveineux ; un relais par VACV 500 mg/j a ete prescrit au long cours sans nouvelle recurrence. Ensuite, aucun patient n’a presente de recurrence (suivi median : 30 mois). Conclusion Un traitement par ACV intraveineux avec relais par VACV semble etre associe a une bonne reponse clinique chez les patients presentant une meningite herpetique symptomatique. La duree de tels traitements reste a mieux evaluer.

There is increasing evidence to support the role of infectious agents in the progression of Alzheimer's disease (AD), especially Helicobacter pylori (H. pylori). The impact of Helicobacter infection on the brain of non-AD predisposed mice was studied. For that, C57BL/6J mice were infected by oral gavage with H. pylori SS1 (n = 6) and Helicobacter felis (H. felis) (n=6) or not infected (n = 6) for evaluation of neuroinflammation (anti-GFAP and anti-iba1 immunohistochemistry) and amyloid-β deposition (thioflavin-S stain and anti-Aβ immunohistochemistry). After 18-month of infection, H. pylori SS1 and H. felis infection induced a strong gastric inflammation compared to non-infected mice, but did not induce brain neuroinflammation or amyloid-β deposition.

Introduction L’arterite giganto-cellulaire est une maladie systemique bien decrite chez le sujet âge au pronostic ophtalmologique reserve. Le diagnostic peut etre difficile en raison de signe clinique trompeur ou aspecifique. Observation Une patiente de 89 ans est hospitalisee en geriatrie pour diplopie binoculaire intermittente avec douleurs retro-orbitaires et cephalees frontales depuis plusieurs jours. Ses antecedents sont une cardiopathie valvulaire avec une stenose aortique et une insuffisance mitrale, une sigmoidite diverticulaire et une phakoemulsification bilaterale. La patiente est autonome et vit a domicile. A l’admission, la patiente est subfebrile a 38,1 °C sans anomalie a l’examen neurologique ni ophtalmologique (mesure de l’acuite visuelle, examen des segments anterieur et posterieur, prise de pression intra-oculaire, test oculomoteur et analyse du champ visuel). L’examen physique ne retrouve que le souffle aortique connu et des arteres temporales proeminentes, les pouls temporaux sont abolis. L’ECG ne montre pas de fibrillation auriculaire. Le bilan biologique retrouve un syndrome inflammatoire biologique (CRP : 194 mg/L, n Discussion L’AGC est une maladie classiquement decrite, rare dans la population generale mais dont l’incidence augmente avec l’âge (incidence annuelle 3 a 5 fois plus importante apres 50 ans : 9,4 cas pour 100 000 habitants/an en France) [1] . L’atteinte ophtalmologique au cours de l’AGC survient chez 15 % des patients principalement sous la forme de neuropathie optique ischemique anterieure, de nevrite optique retrobulbaire ou de sclerite anterieure. Cette observation est didactique pour 2 raisons. La premiere est la presence d’une diplopie binoculaire intermittente comme dans 5 % des AGC. Cette diplopie est le plus souvent expliquee par une ischemie des muscles ou des nerfs oculomoteurs. La presence d’une diplopie binoculaire associee a une claudication de la mâchoire augmente la probabilite d’AGC chez les patients adresses pour biopsie de l’artere temporale. La presence d’une diplopie au diagnostic pourrait etre un signe de risque de perte visuelle au cours de l’AGC. Le diagnostic de diplopie binoculaire intermittente repose essentiellement sur un interrogatoire scrupuleux (image dedoublee de l’objet regarde avec les 2 yeux apparaissant le plus souvent quelques secondes) puisque le signe clinique peut etre absent lors de la consultation. L’accident ischemique transitoire, a fortiori chez le sujet âge, doit etre discute comme diagnostic differentiel, les 2 pathologies etant des urgences therapeutiques. Les bolus de corticoides IV representent le standard de prise en charge du fait de la localisation ophtalmologique. La seconde est l’epaississement scleral posterieur bilateral sur l’IRM en faveur d’une sclerite posterieure bilaterale peu symptomatique. La sclerite posterieure est connue pour etre associee a des nombreuses maladies systemiques comme la polyarthrite rhumatoide le granulomatose avec polyangeite, les spondylarthrites ankylosantes, l’arthrite psoriasique, la sarcoidose, la maladie de Behcet ou encore le syndrome de Cogan [2] . En raison du fond d’œil normal, le diagnostic de sclerite posterieure ne peut etre entierement pose mais l’association d’une douleur retro-orbitaire bilaterale avec l’epaississement scleral posterieur bilateral a l’IRM evoluant favorablement sous corticotherapie renforce la suspicion de sclerite posterieure bilaterale pauciclinique. A notre connaissance, un seul autre cas de sclerite posterieure bilaterale associee a une AGC a ete decrit [3] . Conclusion Nous rapportons ici le cas d’une AGC revelee par une diplopie binoculaire intermittente associee a une sclerite posterieure bilaterale. Le diagnostic d’AGC devrait etre systematiquement evoque devant une ou l’autre de ces anomalies chez un patient âge puisque le pronostic depend d’une prise en charge en urgence.

Primary human dendritic cells (DC) were used to explore the inflammatory effectors, including cytokines and microRNAs, regulated by Helicobacter pylori. In a 48 h ex-vivo co-culture system, both H. pylori B38 and B45 strains activated human DCs and promoted a strong inflammatory response characterized by the early production of pro-inflammatory TNF and IL-6 cytokines, followed by IL-10, IL-1ß and IL-23 secretion. IL-23 was the only cytokine dependent on the cag pathogenicity island status of the bacterial strains. DC activation and cytokine production were accompanied by an early miR-146a upregulation followed by a strong miR-155 induction, which mainly controlled TNFα production. These results pave the way for further investigations into the nature of H. pylori antigens and the subsequently activated signaling pathways involved in the inflammatory response to H. pylori infection, the deregulation of which may likely contribute to gastric lymphomagenesis.

In the last year, several diseases from outside of the gastrointestinal tract have been associated with Helicobacter pylori infection. Indeed, this bacterium produces a low-grade inflammatory state, induces molecular mimicry mechanisms, and interferes with the absorbance of nutrients and drugs possibly influencing the occurrence or the evolution of many diseases. In addition to its role in some hematologic conditions, such as immune thrombocytopenic purpura, idiopathic sideropenic anemia, and vitamin B12 deficiency, which were included in the current guidelines, several other conditions such as cardiovascular diseases, diabetes mellitus, hepatobiliary diseases, and neurologic disorders have also shown promising results.

Objective.To evaluate the efficacy compared to the relapse risk and tolerance of systematic rituximab (RTX) infusions as maintenance therapy for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), who entered remission taking conventional immunosuppressants or RTX.Methods.A retrospective study of the main clinical characteristics, outcomes, and RTX tolerance of patients who had received ≥ 2 RTX maintenance infusions in our center, regardless of induction regimen, between 2003 and 2010.Results.We identified 28 patients [4 MPA and 24 GPA; median age 55.5 yrs (range 18–78); 17 (60%) males] who received a median of 4 (range 2–10) RTX maintenance infusions, with median followup of 38 months (range 21–97) since diagnosis or last flare. None experienced a RTX infusion-related adverse event; 15 patients (among the 21 with available data) had hypogammaglobulinemia (predominantly IgM) prior to their last RTX maintenance infusion; 3 had infectious events (1 cutaneous abscess, 1 otitis, 1 fatal H1N1 flu). Two patients suffered pulmonary relapses shortly before a planned RTX maintenance infusion (both had increased antineutrophil cytoplasmic antibody levels and 1 had CD19+ lymphocyte reconstitution).Conclusion.Rituximab maintenance therapy was well tolerated but did not completely prevent relapses and persistent “grumbling” disease. These preliminary results remain to be confirmed by a randomized controlled trial currently in progress.