Publications by authors named "Claire Roubaud Baudron"

30 Publications

  • Page 1 of 1

Outpatient Subcutaneous Antimicrobial Therapy (OSCAT) as a Measure to Improve the Quality and Efficiency of Healthcare Delivery for Patients With Serious Bacterial Infections.

Front Med (Lausanne) 2020 23;7:585658. Epub 2020 Dec 23.

CHU de Bordeaux, Pôle de Gérontologie Clinique, Bordeaux, France.

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.
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http://dx.doi.org/10.3389/fmed.2020.585658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785854PMC
December 2020

The Reply.

Am J Med 2020 08;133(8):e445

CHU de Bordeaux, Pôle de Gérontologie Clinique, F-33000 Bordeaux, France; Univ. Bordeaux, INSERM UMR 1034 BaRITOn, F-33000 Bordeaux, France. Electronic address:

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http://dx.doi.org/10.1016/j.amjmed.2020.04.010DOI Listing
August 2020

A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis.

Genome Med 2020 07 25;12(1):65. Epub 2020 Jul 25.

Departments of Medicine and Microbiology, New York University School of Medicine (NYUSM), New York, NY, 10016, USA.

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.
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http://dx.doi.org/10.1186/s13073-020-00764-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382806PMC
July 2020

Subcutaneous Antibiotic Therapy: The Why, How, Which Drugs and When.

J Am Med Dir Assoc 2021 Jan 14;22(1):50-55.e6. Epub 2020 Jul 14.

CHU de Bordeaux, Pôle de Gérontologie Clinique, Bordeaux, France; Université Bordeaux, INSERM UMR 1053 BaRITOn, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jamda.2020.04.035DOI Listing
January 2021

Quality of Life: Psychological Symptoms-Effects of a 2-Month Healthy Diet and Nutraceutical Intervention; A Randomized, Open-Label Intervention Trial (RISTOMED).

Nutrients 2020 Mar 18;12(3). Epub 2020 Mar 18.

Department Gastroenterology and Hepatology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.

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%, = 0.001; B: -32.5%, = 0.023; C: -42.8%, = 0.004; and D: -33.3%, = 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%, = 0.021; B, -46.7%, = 0.024; C, -52.2%, = 0.039; D, -43.8%, = 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.
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http://dx.doi.org/10.3390/nu12030800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146172PMC
March 2020

Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection.

mBio 2019 12 24;10(6). Epub 2019 Dec 24.

Department of Medicine, New York University Langone Medical Center, New York, New York, USA

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 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. 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 -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.
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http://dx.doi.org/10.1128/mBio.02820-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935859PMC
December 2019

Alzheimer's Disease and Helicobacter pylori Infection: Inflammation from Stomach to Brain?

J Alzheimers Dis 2020 ;73(2):801-809

University of Bordeaux, UMR BaRITOn, INSERM 1053, Bordeaux, France.

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. pylori-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.
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http://dx.doi.org/10.3233/JAD-190496DOI Listing
November 2020

Managing infective endocarditis in older patients: do we need a geriatrician?

Aging Clin Exp Res 2019 Nov 22. Epub 2019 Nov 22.

CHU de Bordeaux, Pôle de Gérontologie Clinique, University of Bordeaux, 33000, Bordeaux, France.

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.
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http://dx.doi.org/10.1007/s40520-019-01400-6DOI Listing
November 2019

Emerging viruses in older population Chikungunya, West Nile fever and Dengue.

Aging Clin Exp Res 2019 Nov 18. Epub 2019 Nov 18.

CHU Bordeaux, Pôle de Gérontologie Clinique, 33000, Bordeaux, France.

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http://dx.doi.org/10.1007/s40520-019-01389-yDOI Listing
November 2019

Is the subcutaneous route an alternative for administering ertapenem to older patients? PHACINERTA study.

J Antimicrob Chemother 2019 12;74(12):3546-3554

CHU Bordeaux, Service Pharmacie à Usage Intérieur, département de Pharmacie Clinique, F-33000 Bordeaux, France.

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.
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http://dx.doi.org/10.1093/jac/dkz385DOI Listing
December 2019

Association of Seropositivity to Borrelia burgdorferi With the Risk of Neuropsychiatric Disorders and Functional Decline in Older Adults: The Aging Multidisciplinary Investigation Study.

JAMA Neurol 2020 02;77(2):210-214

University Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France.

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.
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http://dx.doi.org/10.1001/jamaneurol.2019.3292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777246PMC
February 2020

Acute Clostridioides difficile Infection in Hospitalized Persons Aged 75 and Older: 30-Day Prognosis and Risk Factors for Mortality.

J Am Med Dir Assoc 2020 01 17;21(1):110-114. Epub 2019 Sep 17.

Pôle de Gériatrie, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, Poitiers, France; Centre d'Investigation Clinique CIC 1402, INSERM, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, Poitiers, France.

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.
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http://dx.doi.org/10.1016/j.jamda.2019.07.002DOI Listing
January 2020

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Blood 2019 12;134(24):2209-2217

Service d'Hématologie, AP-HP.6, Paris, France; and.

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 or ≥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 × 103/mm3 [9-57] vs 13 × 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.
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http://dx.doi.org/10.1182/blood.2019000748DOI Listing
December 2019

Review: Helicobacter pylori and extragastric diseases.

Helicobacter 2019 Sep;24 Suppl 1:e12636

CHU Bordeaux, Pôle de Gérontologie Clinique, Bordeaux, France.

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.
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http://dx.doi.org/10.1111/hel.12636DOI Listing
September 2019

Atypical Presentation of Bacteremia in Older Patients Is a Risk Factor for Death.

Am J Med 2019 11 1;132(11):1344-1352.e1. Epub 2019 Jun 1.

CHU Bordeaux, Pôle de Gérontologie Clinique, Bordeaux, France; Université de Bordeaux, INSERM UMR 1053 BaRITOn, Bordeaux, France. Electronic address:

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°C or <36°C, chills, or hypotension. Mortality and dependence for activities of daily living (ADL) were recorded at 1 week (D7) and 3 months (D90).

Results: Among the 151 patients (mean age 85.4±5.8 years) enrolled, atypical presentation prevalence was 21.2%. D7 and D90 mortality rates were 7.9% and 40.0%, respectively. Atypical presentation was independently associated with D7 (odds ratio (OR) 4.46, 95% confidence interval (CI) 1.04-19.24) and D90 mortality (OR 3.76, 95% CI 1.30-10.92) after controlling for other prognostic factors. Patients with diabetes and those infected with Staphylococcus aureus were more likely to have atypical signs of infection. ADL score decreased from 3.6±2.0 before bacteremia to 2.8±2.1 at D90 (P <0.001).

Conclusion: Patients who are older with bacteremia have poor vital and functional prognoses in the short and long terms. The absence of typical signs of infection is associated with mortality. Blood culture should be considered for patients who are older, especially with diabetes with acute unexplained clinical manifestations.
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http://dx.doi.org/10.1016/j.amjmed.2019.04.049DOI Listing
November 2019

Detecting both current and prior Helicobacter pylori infection is important to assess its impact on dementia.

Alzheimers Dement 2019 05 8;15(5):721-722. Epub 2019 Mar 8.

University of Bordeaux, Population Health Research Center, INSERM UMR 1219, Bordeaux, France.

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http://dx.doi.org/10.1016/j.jalz.2018.12.020DOI Listing
May 2019

Discrepancy Between Equations Estimating Kidney Function in Geriatric Care: A Study of Implications for Drug Prescription.

Drugs Aging 2019 02;36(2):155-163

CHU Bordeaux, Département de Gérontologie Clinique, Avenue du Haut-Lévêque, F-33604, Pessac, France.

Background: 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 (eGFR). The implications of these discrepancies for drug prescription have so far been assessed only for a few selected molecules.

Objective: 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 eGFR estimates of kidney function.

Methods: 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 eGFR.

Results: 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 eGFR estimates of kidney function, 4% received a drug with a relative contraindication according to eCrCl but not eGFR, 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.

Conclusion: 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.
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http://dx.doi.org/10.1007/s40266-018-0618-3DOI Listing
February 2019

Tolerance of subcutaneously administered antibiotics: a French national prospective study.

Age Ageing 2017 01;46(1):151-155

Pôle de Gériatrie, Centre Hospitalier Universitaire de Poitiers, Université de Poitiers, F-86000 Poitiers, France

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.
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http://dx.doi.org/10.1093/ageing/afw143DOI Listing
January 2017

Managing infective endocarditis in the elderly: new issues for an old disease.

Clin Interv Aging 2016 2;11:1199-206. Epub 2016 Sep 2.

Infectious Diseases Department, Centre Hospitalier Annecy-Genevois, Annecy, France.

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.
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http://dx.doi.org/10.2147/CIA.S101902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015881PMC
February 2017

[Alzheimer's disease and Helicobacter pylori infection: a possible link?].

Geriatr Psychol Neuropsychiatr Vieil 2016 Mar;14(1):86-94

Université de Bordeaux, Bordeaux, France, Inserm U853, Bordeaux, France, Pôle de gérontologie clinique, CHU Hôpitaux de Bordeaux, Bordeaux, France.

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.
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http://dx.doi.org/10.1684/pnv.2016.0584DOI Listing
March 2016

[Alzheimer's disease: the infectious hypothesis].

Geriatr Psychol Neuropsychiatr Vieil 2015 Dec;13(4):418-24

Université de Bordeaux, Bordeaux, France, Inserm U853, Bordeaux, France, Pôle de gérontologie clinique, CHU Hôpitaux de Bordeaux, Bordeaux, France.

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.
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http://dx.doi.org/10.1684/pnv.2015.0574DOI Listing
December 2015

An Eighteen-Month Helicobacter Infection Does Not Induce Amyloid Plaques or Neuroinflammation in Brains of Wild Type C57BL/6J Mice.

J Alzheimers Dis 2015 ;45(4):1045-50

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.
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http://dx.doi.org/10.3233/JAD-143129DOI Listing
March 2016

Extragastric diseases and Helicobacter pylori.

Helicobacter 2013 Sep;18 Suppl 1:44-51

Université de Bordeaux, Laboratoire de Bactériologie, Bordeaux, France; Pôle de Gérontologie Clinique, Bordeaux, France; INSERM U853, Bordeaux, France.

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.
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http://dx.doi.org/10.1111/hel.12077DOI Listing
September 2013

Inflammatory cytokine and microRNA responses of primary human dendritic cells cultured with Helicobacter pylori strains.

Front Microbiol 2013 20;4:236. Epub 2013 Aug 20.

Bacteriology Laboratory, Université Bordeaux Bordeaux, France ; Institut National de la Santé et de la Recherche Médicale, U853 Bordeaux, France.

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 TNFα and IL-6 cytokines, followed by IL-10, IL-1β, 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.
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http://dx.doi.org/10.3389/fmicb.2013.00236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747313PMC
August 2013

Change of the dependent variable.

Neurobiol Aging 2013 Jun 4;34(6):e1. Epub 2013 Feb 4.

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http://dx.doi.org/10.1016/j.neurobiolaging.2012.12.022DOI Listing
June 2013

Does Helicobacter pylori infection increase incidence of dementia? The Personnes Agées QUID Study.

J Am Geriatr Soc 2013 Jan 18;61(1):74-8. Epub 2012 Dec 18.

INSERM, U853, F-33000, Bordeaux, France.

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 Agées 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.
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http://dx.doi.org/10.1111/jgs.12065DOI Listing
January 2013

Impact of chronic Helicobacter pylori infection on Alzheimer's disease: preliminary results.

Neurobiol Aging 2012 May 1;33(5):1009.e11-9. Epub 2011 Dec 1.

Institut National de la Sante et de la Recherche Medicale U853, Bordeaux, France.

Recent case-control studies reported an association between H. pylori infection and Alzheimer's disease (AD). Our aim was to compare cognitive impairment, neuroinflammation, and cerebrovascular lesion load in a group of AD patients according to their H. pylori status. For the 53 AD patients included, we assessed: clinical data (vascular comorbidities and cognitive assessment), biological data (especially fibrinogen, homocysteine levels, apolipoprotein E4 genotype; cerebrospinal fluid [CSF] total tau protein [Tau], phospho-tau(181) protein [pTau(181)]), and amyloid beta peptide levels, serum/CSF-cytokines (interleukin [IL]-1β, IL-6, IL-8, tumor necrosis factor [TNF]-α) and pepsinogen I/pepsinogen II (PgI/PgII) ratio, and cerebrovascular lesion load (magnetic resonance imaging [MRI] fluid-attenuated inversion recovery [FLAIR] with the Fazekas and Schmidt scale). H. pylori infection was diagnosed by enzyme-linked immunosorbent assay (ELISA) and immunoblot test. H. pylori infection was associated with a decreased Mini Mental State Examination (MMS) (p = 0.024), and higher CSF pTau(181) (p = 0.014) and tau (p = 0.021) levels. A decreased PgI/II ratio (i.e., an increased gastric atrophy) was associated with the infection (p = 0.005). Homocysteine levels were positively correlated to Fazekas score (r = 0.34; p = 0.032) and to H. pylori immunoglobulin (Ig)G levels (r = 0.44; p = 0.001). Higher CSF cytokine levels (IL-8, p = 0.003; TNF-α, p = 0.019) were associated with the infection, but systemic inflammation results were controversial. Finally, in multivariate analysis, a lower MMSE score (odds ratio [OR], 0.83 [0.72-0.97]; p = 0.017), plasma IL-1β level (OR, 0.31 [0.11-0.87]; p = 0.025), an increased gastric atrophy, i.e., a lower PgI/PgII ratio (OR, 0.63 [0.43-0.93]; p = 0.020) were still associated with the infection. AD patients infected by H. pylori tended to be more cognitively impaired. Studies are needed to attest to the impact of H. pylori infection on AD course, especially on cerebrovascular lesions and neuroinflammation.
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http://dx.doi.org/10.1016/j.neurobiolaging.2011.10.021DOI Listing
May 2012

Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis.

J Rheumatol 2012 Jan 15;39(1):125-30. Epub 2011 Nov 15.

Department of Internal Medicine, Hôpital Cochin, 27 rue du faubourg Saint-Jacques, 75679 Paris Cedex 14, France.

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.
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http://dx.doi.org/10.3899/jrheum.110143DOI Listing
January 2012

Lymph node tuberculosis and paradoxical evolution.

J Am Geriatr Soc 2010 Jan;58(1):192-3

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http://dx.doi.org/10.1111/j.1532-5415.2009.02635.xDOI Listing
January 2010

[Herpes simplex virus meningitis in 11 patients].

Med Mal Infect 2008 Mar 10;38(3):141-5. Epub 2008 Jan 10.

Département de Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpêtrière, Paris, France.

Method: We reviewed retrospectively the demographic, clinical, biological characteristics and outcomes of 11 patients with HSV meningitis.

Results: Among the 11 patients, six were infected with HIV, four had a documented history of genital herpes, and one recurrent meningitis. In all cases, the onset of symptoms was abrupt, with severe headache and fever. On admission, 9/11 patients had severe meningismus; two patients had HSV anogenital ulcerations. CSF analysis showed in every case a significant increased of leukocytes with a lymphocytic pleocytosis, a mild elevated protein level and a normal glucose level. HSV was detected in the CSF in every case by PCR: the typing performed on six patients was positive in every case for HSV-2. Intravenous acyclovir (IV ACV) was started in 10/11 cases (range: 3-10 days), switched to valaciclovir (VACV) (range: 5-7 days); one patient was treated with ACV per os for 10 days. The total resolution of symptoms occurred within 48hours in every case. Two patients presented with recurrent HSV-2 meningitis in the next two months, with favorable outcome under IV ACV: a switch to long term VACV 500mg/day was prescribed without any recurrence. No patient presented with recurrence after a median follow-up of 30 months.

Conclusion: Early recognition and treatment might improve the outcome of such infections. Adjunctive oral VACV after IV ACV treatment seems to be associated with a good clinical response in patients presenting with HSV meningitis. The duration of such treatments, including prophylactic treatments to prevent recurrent episodes must be better documented.
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http://dx.doi.org/10.1016/j.medmal.2007.11.011DOI Listing
March 2008