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Objectives: To describe the real-life use of temocillin for non-urinary tract infections, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure., Method: Retrospective multicentric study in 14 tertiary care hospitals, including all patients who received at least one dose of temocillin for ESBL infections from 1 January 2016 to 31 December 2021 for non-urinary tract infections. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. Logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure., Results: Data on 163 infection episodes were collected; 133 were due to ESBL-producing Enterobacterales and 128 were included in the effectiveness analysis. Median (IQR) age was 61 (53-70) years and 61.7% of patients were male. Main indications were lower respiratory tract infection (LRTI; 28.9%), intra-abdominal infections (IAI; 28.1%) and cutaneous infections (12.5%). The main bacteria involved were Klebsiella pneumoniae (48.4%), Escherichia coli (25.0%) and Enterobacter cloacae (24.2%). Polymicrobial infections occurred in 45.3% of cases. Temocillin was used as monotherapy in 86/128 (67.2%). Failure was found in 36/128 (28.1%) cases. In multivariable analysis, the only factor associated with failure was initial severity of the episode [adjusted OR 3.0 (95% CI: 1.06-8.69)]., Conclusions: During non-urinary tract infections, the main use of temocillin was for LRTIs and IAIs due to ESBL-producing E. coli and K. pneumoniae . The main risk factor for failure was initial severity of the disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: We evaluated the effect of fecal microbiota transplantation (FMT) on the clearance of carbapenemase-producing Enterobacterales (CPE) carriage., Methods: We performed a prospective, multi-center study, conducted among patients who received a single dose of FMT from one of four healthy donors. The primary endpoint was complete clearance of CPE carriage two weeks after FMT with a secondary endpoint at three months. Shotgun metagenomic sequencing was performed to assess gut microbiota composition of donors and recipients before and after FMT., Results: Twenty CPE-colonized patients were included in the study, where post-FMT 20% (n = 4/20) of patients met the primary endpoint and 40% (n = 8/20) of patients met the secondary endpoint. Kaplan-Meier curves between patients with FMT intervention and the control group (n = 82) revealed a similar rate of decolonization between groups. Microbiota composition analyses revealed that response to FMT was not donor-dependent. Responders had a significantly lower relative abundance of CPE species pre-FMT than non-responders, and 14 days post-FMT responders had significantly higher bacterial species richness and alpha diversity compared to non-responders (p < 0.05). Responder fecal samples were also enriched in specific species, with significantly higher relative abundances of Faecalibacterium prausnitzii, Parabacteroides distasonis, Collinsella aerofaciens, Alistipes finegoldii and Blautia&#95;A sp900066335 (q<0.01) compared to non-responders., Conclusion: FMT administration using the proposed regimen did not achieve statistical significance for complete CPE decolonization but was correlated with the relative abundance of specific bacterial taxa, including CPE species., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of interests A.R.W, G.G, and S.C are employees of Vedanta Biosciences and have an equity interest in the company. Vedanta Biosciences holds patents related to this work. The authors vouch for the accuracy and completeness of the data and data analyses. This content is solely the responsibility of the authors., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This narrative review aims to discuss the main interest in and cautions associated with the use of expired antibiotics in the context of repeated shortages, notably in Europe. Articles concerning the topic of expiry dates related to antibiotic use were reviewed using keywords in the PubMed ® /MEDLINE and Google Scholar databases to identify the most extensive evidence-based documentation. The present review evaluates the potential interest and efficacy of using expired drugs and their possible related adverse events. Overall, in the context of drug shortages, expiry dates could be safely extended for at least one year for most solid antibiotics (tablets or powder) used in daily clinical practice, as long as they are stored under the right conditions, in accordance with the summary of product characteristics.

Background: Proton pump inhibitors (PPIs) are largely used in older adults and data are needed in off-label indications, such as the prevention of upper gastrointestinal bleeding (UGIB) in patients receiving oral anticoagulants (OACs). This study aimed to assess whether PPIs reduce the risk of UGIB in patients initiating oral anticoagulation., Methods: We conducted a longitudinal study based on the French national health database. The study population included 109,693 patients aged 75-110 years with a diagnosis of atrial fibrillation who initiated OACs [vitamin K antagonist (VKA) or direct OAC (DOAC)] between 2012 and 2016. We used multivariable Cox models weighted by inverse of probability of treatment to estimate the adjusted hazard ratio (aHR) of UGIB between PPI users and nonusers over a 6- and 12-month follow-up., Results: PPI users represented 23% of the study population (28% among VKA initiators and 17% among DOAC initiators). The mean age (83 ± 5.3 years) and proportion of women (near 60%) were similar between groups. The risk of UGIB in the first 6 months after initiation of OAC decreased by 20% in PPI users compared with PPI nonusers [aHR 6 months = 0.80, 95% confidence interval (CI) 0.65-0.98], but was not significantly modified when the follow-up was extended to 12 months (aHR 12 months = 0.90, 95% CI 0.76-1.07), with a stronger effect among patients treated with vitamin K antagonists (aHR 6 months = 0.73, 95% CI 0.58-0.93; aHR 12 months = 0.81, 95% CI 0.67-0.99)., Conclusions: This study suggests that PPIs were associated with reduced risk of gastrointestinal bleeding after initiation of oral anticoagulation in older patients with atrial fibrillation, particularly within 6 months after initiation of an antivitamin K antagonist., (© 2023. The Author(s).)

Purpose: Potentially inappropriate medications (PIMs) have become a major issue in improving prescribing practices and reducing the risk of adverse drug events in older people. However, very few studies have compared exposition to PIMs controlling for differences in demographic and health between nursing home residents (NHRs) and community-dwelling older adults (CDOAs). This study aimed to assess the prescribing pattern of PIMs between NHRs and CDOAs., Methods: We conducted a cross-sectional study over three months in 2019 using the French Health Insurance databases. The study population included 274 971 NHRs and 4 893 721 CDOAs aged 75 years or over. The prevalence ratio (PR) between NHRs and CDOAs of 17 PIM indicators, based on the Beers and STOPP criteria lists, was assessed using multivariable robust Poisson regression adjusted for age, sex, diseases, and polypharmacy., Results: During the study period, 54% of NHRs and 29% of CDOAs received at least one PIM. After adjustment, the prevalence of PIMs was 33% higher among NHRs compared to CDOAs (aPR = 1.33; 95% CI [1.33-1.34]). NHRs received PIMs related to benzodiazepines (aPR = 1.43; 95% CI [1.42-1.43]), anticholinergic drugs (aPR = 1.29; 95% CI [1.27-1.31]), and at least three central nervous system-active drugs (aPR = 1.94; 95% CI [1.92-1.96]) more frequently. Prevalence of PIMs related to non-steroidal anti-inflammatory drugs (aPR = 0.50; 95% CI [0.48-0.52]) and long-acting benzodiazepines (aPR = 0.84; 95% CI [0.82-0.85]) was lower among NHRs., Conclusion: The NHRs were at greater risk for PIM than CDOAs, although differences exist according to the category of PIMs. As the population is aging, it is essential to promote and evaluate interventions in NHs and the community to enhance medication optimization., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Temocillin is a β-lactam that is not hydrolysed by ESBLs., Objectives: To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure., Methods: Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure., Results: Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ± 15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6)., Conclusions: The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae , with a favourable clinical outcome. The main risk factor for failure was neurological disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Proton pump inhibitors (PPIs) have become the agents of choice for acid-related diseases. In some clinical situations, PPI therapy by oral or intravenous route may be difficult especially among elderly and patients in palliative care. Off-label PPI subcutaneous injection could be the last alternative to improve patient relief, despite limited published data. We report a case of linitis plastica, peritoneal carcinomatosis and occlusive syndrome who suffered from painful regurgitations which rapidly improved after subcutaneous pantoprazole. No related adverse effects were observed during PPI therapy. Despite some limitations, this report suggests that off-label subcutaneous pantoprazole could be an interesting alternative route when intravenous infusion may be difficult or harmful for elderly and patients in palliative care. Nevertheless, clinical safety and efficiency data on larger populations are needed to validate this use in such population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare the impact of a care bundle including medication reconciliation at discharge by a pharmacist versus standard of care, on continuity of therapeutic changes between hospital and primary care and outcome of patients, within 1 month after discharge., Methods: Randomised controlled trial in 120 adult patients with at least one chronic disease and three current medications before admission, hospitalised in an infectious disease department of a tertiary hospital and discharged home. Patients were randomly assigned (1:1) to receive a discharge care bundle including medication reconciliation, counselling session and documentation transfer to primary care physician (PCP) (intervention group) or standard of care (control group). Primary outcome was the proportion of in-hospital prescription changes, not maintained by the PCP, 1 month after discharge. Secondary outcome measures included the proportion of patients experiencing early PCP's consultation, hospital readmissions or adverse reactions within 1-month postdischarge and cost of discharge prescriptions., Results: Baseline characteristics were comparable between the two groups. One month after discharge, the proportion of in-hospital prescription changes, not maintained by the PCP, was 11% in the intervention group versus 24% in the control group (P = .007). The median delay before PCP's consultation was longer in the intervention group (30.5 vs 19.5 days, P = .013), there were fewer patients readmitted to hospital (3.4% vs 20.7%, P = .009, odds ratio (OR) = 0.13 [0.02-0.53]) and fewer patients who suffered from adverse drug reaction (7.0% vs 22.8%, P = .04, OR = 0.26 [0.07-0.78])., Conclusion: This care bundle resulted in the reduction of treatment changes between hospital discharge and primary care., (© 2021 John Wiley & Sons Ltd.)

Bloodstream infections (BSIs) among older patients are frequent with high rate of mortality. Infections with multidrug-resistant organisms (MDRO) are associated with higher mortality than with susceptible microorganisms. We aimed to evaluate the prevalence of MDRO infection during BSI in older population and the factors associated with unfavorable outcome. This study is a retrospective cohort of all BSI episodes occurring among older patients (> 65yo), from April 1, 2010, to December 31, 2016, in a French university hospital for geriatric medicine. A total of 255 BSI episodes were analyzed. Mean age was 86.3±6.5 years, and sex ratio (M/F) was 0.96. Main comorbidities were orthopedic device (26.7%), active neoplasia (24.3%), and diabetes mellitus (18.4%). Main primary sites of infection were urinary tract infections (56.9%), respiratory tract infections (10.6%), intra-abdominal infections (7.1%), and skin and soft tissue infections (4.7%). Main bacteria identified were Escherichia coli (45.1%), Staphylococcus aureus (14.1%), enterococci (10.7%), coagulase-negative staphylococci (CoNS) (5.5%), and streptococci (5.1%). MDROs were involved in 17.2% of BSI (gram-negative bacilli: 9.0%; CoNS: 4.3%; and methicillin-resistant S. aureus (MRSA): 3.9%). The main factor associated with MDRO BSI was colonization with MDRO (OR=6.29; 95%CI=2.9-14.32). Total mortality was 18.4% and significantly higher in case of initial severity (OR=3.83; 95%CI=1.75-8.38), healthcare-associated infection (OR=5.29; 95%CI=1.11-25.30), and MRSA BSI (OR=9.16; 95%CI=1.67-50.16). BSI due to MDRO is frequent in older population and is strongly associated with carriage of MDRO. Healthcare-associated BSI, severe episodes, and BSI due to MRSA are associated with unfavorable outcome. In these cases, a broad-spectrum antibiotic should be promptly initiated., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders. Today there is no consensus about the management of sialorrhoea, but off-label use of ophthalmic atropine eyedrop administered sublingually may offer benefits, despite limited safety data. We report 2 cases of atropine overdose after sublingual administration illustrating that atropine can expose to severe adverse effects when administered sublingually. The noncompartmental pharmacokinetic study of atropine performed in 1 patient highlighted that systemic absorption of sublingual atropine was effective (C max [1 h] = 2.2 ng mL -1 ; approximately) after a single dose of 1 mg., (© 2021 British Pharmacological Society.)

The medication circuit is a complex, transversal and risky process. It involves interdependent clinical and logistical stages. Its automation and computerisation are real levers for securing the patient's medication management and optimising the organisation of care. It allows care staff to free up precious time to provide care, particularly in geriatrics., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Objective: Mycophenolate mofetil is widely used in kidney transplant recipients. Mycophenolate mofetil is hydrolysed by blood esterases to mycophenolic acid (MPA), the active drug. Although MPA therapeutic drug monitoring has been recommended to optimise the treatment efficacy by the area under the plasma concentration vs time curve, little is known regarding MPA concentrations in peripheral blood mononuclear cells, where MPA inhibits inosine monophosphate dehydrogenase. This study aimed to build a pharmacokinetic model using a population approach to describe MPA total and unbound concentrations in plasma and into peripheral blood mononuclear cells in 78 adult kidney transplant recipients receiving mycophenolate mofetil therapy combined with tacrolimus and prednisone., Methods: Total and unbound plasma concentrations and peripheral blood mononuclear cell concentrations were assayed. A three-compartment model, two for plasma MPA and one for peripheral blood mononuclear cell MPA, with a zero-order absorption and a first-order elimination was used to describe the data., Results: Mycophenolic acid average concentrations in peripheral blood mononuclear cells were well above half-maximal effective concentration for inosine monophosphate dehydrogenase and no relationship was found with the occurrence of graft rejection. Three covariates affected unbound and intracellular MPA pharmacokinetics: creatinine clearance, which has an effect on unbound MPA clearance, human serum albumin, which influences fraction unbound MPA and the ABCB1 3435 C>T (rs1045642) genetic polymorphism, which has an effect on MPA efflux transport from peripheral blood mononuclear cells., Conclusion: This population pharmacokinetic model demonstrated the intracellular accumulation of MPA, the efflux of MPA out of the cells being dependent on P-glycoprotein transporters. Nevertheless, further studies are warranted to investigate the relevance of MPA concentrations in peripheral blood mononuclear cells to dosing regimen optimisation.

Background: Complement pathway inhibition may provide benefit for severe acute respiratory illnesses caused by viral infections such as COVID-19. We present results from a nonrandomized proof-of-concept study of complement C5 inhibitor eculizumab for treatment of severe COVID-19., Methods: All patients ( N  = 80) with confirmed SARS-CoV-2 infection and severe COVID-19 admitted to our intensive care unit between March 10 and May 5, 2020 were included. Forty-five patients were treated with standard care and 35 with standard care plus eculizumab through expanded-access emergency treatment. The prespecified primary outcome was day-15 survival. Clinical laboratory values and biomarkers, complement levels, and treatment-emergent serious adverse events (TESAEs) were also assessed., Findings: At day 15, estimated survival was 82.9% (95% CI: 70.4%‒95.3%) with eculizumab and 62.2% (48.1%‒76.4%) without eculizumab (log-rank test, P  = 0.04). Patients treated with eculizumab experienced a significantly more rapid decrease in lactate, blood urea nitrogen, total and conjugated bilirubin levels and a significantly more rapid increase in platelet count, prothrombin time, and in the ratio of arterial oxygen tension over fraction of inspired oxygen versus patients treated without eculizumab. Eculizumab-associated changes in complement levels, laboratory values, and biomarkers were consistent with terminal complement inhibition, reduced hypoxia, and decreased inflammation. TESAEs of special interest occurring in >5% of patients treated with/without eculizumab were ventilator-associated pneumonia (51%/24%), bacteremia (11%/2%), gastroduodenal hemorrhage (14%/16%), and hemolysis (3%/18%)., Interpretation: Findings from this proof-of-concept study suggest eculizumab may improve survival and reduce hypoxia in patients with severe COVID-19. Randomized studies evaluating the efficacy and safety of this treatment approach are needed., Funding: Programme d'Investissements d'Avenir: ANR-18-RHUS60004., Competing Interests: Djillali Annane: reports non-financial support from Alexion Pharmaceuticals Inc. and grants from Programme d'Investissements d'Avenir during the conduct of the study; other (investigator) from Alexion outside the submitted work. Nicholas Heming: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study; other (investigator) from Alexion outside the submitted work. Lamiae Grimaldi-Bensouda: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study. Véronique Frémeaux-Bacchi: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study; grants and personal fees from Alexion, personal fees from Roche, personal fees from Apellis, and personal fees from Biocryps outside the submitted work. Marie Vigan: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study. Anne-Laure Roux: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study. Armance Marchal: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study. Hugues Michelon: reports non-financial support from Alexion Pharmaceuticals Inc, during the conduct of the study. Martin Rottman: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study. Pierre Moine: reports non-financial support from Alexion Pharmaceuticals Inc. during the conduct of the study; non-financial support and other (investigator) from Alexion outside the submitted work., (© 2020 The Author(s).)

Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.g., size, shape, thickness) are likely to influence swallowability. Herein, we used the acceptability reference framework (the ClinSearch acceptability score test (CAST))-a 3D-map juxtaposing two acceptability profiles-to investigate the impact of tablet size on acceptability. We collected 938 observer reports on the tablet intake by patients ≥65 years in hospitals or care homes. As we might expect, tablets could be classified as accepted in older patients without dysphagia ( n = 790), while not in those with swallowing disorders ( n = 146). However, reducing the tablet size had a significant impact on acceptability in this subpopulation: tablets <6.5 mm appeared to be accepted by patients with swallowing disorders. Among the 309 distinct tablets assessed in this study, ranging in size from 4.7 to 21.5 mm, 83% are ≥6.5 mm and consequently may be poorly accepted by institutionalized older people and older inpatients suffering from dysphagia. This underlines the need to develop and prescribe medicines with the best adapted characteristics to reach an optimal acceptability in targeted users.

Midazolam is a short-acting benzodiazepine approved for sedation and anesthesia induction. Recent data suggested that midazolam may also be used in off-label indications such as treatment of behavioral and psychological disturbances in older people. Given the scarcity of published data and a lack of evidence in older people in such indications, midazolam raises concern because it may also cause serious-related adverse events. To provide a better understanding of its real-life use in geriatrics, we examined the prescribing practices of midazolam in French older inpatients. Of the 460 patients aged 65 years and over hospitalized at the time of the study, 21 had a prescription of midazolam (5%) which was mainly prescribed for anxiolysis (n = 12), premedication before painful procedures (n = 5), and agitation (n = 4). Midazolam was often prescribed "as required," and the median duration of prescription was 6 months. This work results in a better knowledge and information about the use of midazolam in older people. These prescribing practices, which are not anecdotal, also plead for age-specific guidelines for the treatment of behavioral and psychological disturbances., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

Background: In institutional care, oral liquid pharmaceutical products are widely prescribed for older patients, especially for those with swallowing disorders. As medicines acceptability is a key factor for compliance in the older population, this study investigated the acceptability of oral liquid pharmaceutical products in this targeted population., Methods: An observational, multicenter, prospective study was conducted in eight geriatric hospitals and eight nursing homes in France. Observers reported several behaviours/events describing the many aspects of acceptability for various pharmaceutical products' uses in patients aged 65 and older. Acceptability scores of oral liquid pharmaceutical products were obtained using an acceptability reference framework (CAST - ClinSearch Acceptability Score Test®): a 3D-map summarizing the different users' behaviors, with two clusters defining the positively and negatively accepted profiles materialized by the green and red zones, respectively., Results: Among 1288 patients included in the core study and supporting the acceptability reference framework, 340 assessments were related to the administration of an oral liquid pharmaceutical product. The mean age of these patients was 87 (Range [66-104y]; SD = 6.7), 68% were women and 16% had swallowing disorders. Globally, the oral liquid pharmaceutical products were classified as "positively accepted," the barycenter of the 340 assessments, along with the entire confidence ellipses surrounding it, were positioned on the green zone of the map. Sub-populations presenting a different acceptability profile have also been identified. For patients with swallowing disorders, the oral liquid pharmaceutical products were classified as "negatively accepted," the barycenter of the 53 assessments along with 87% of its confidence ellipses were associated with this profile. A gender difference was observed for unflavored oral liquids. In women, they were classified "negatively accepted," the barycenter of the 68 assessments with 75% of its confidence ellipses were located in the red zone, while they were classified "positively accepted" in men., Conclusion: This study showed that oral liquid pharmaceutical products are a suboptimal alternative to solid oral dosage forms in patients with swallowing disorders. To ensure an optimal acceptability, prescribers should also consider the presence of a taste-masker in these oral liquids. As highlighted herein, palatability remains crucial in older populations, especially for women.

Palatability is a recognized driver of medicine acceptability in pediatrics but deemed less relevant in older populations due to sensory decline. Preliminary findings from an observational study implicated palatability problems with one Alzheimer's medicine. Among 1517 observer reports combining multiple measures on medicines uses in patients aged over 64, we focused on two original formulations of memantine (Ebixa ® , tablets ( n = 25) and oral solution ( n = 60)). Evaluations were scored with an acceptability reference framework (CAST), the rodent Brief Access Taste Aversion (BATA) model tested aversiveness. Focusing on women treated with Ebixa ® ( n = 54), the oral formulation sub-group was classified as "negatively accepted", while the coated tablet was associated with the "positively accepted" cluster. In men, both formulations belonged to the "positively accepted" profile. Using BATA, the original oral solution was categorized as highly aversive/untolerated while solutions of excipients only were well tolerated. Furthermore, the number of licks was significantly lower in female than in male rats. These results revealed that medicine palatability remains important for acceptability in older populations. Moreover, converging results from humans and animal models highlighted that palatability profiles can significantly vary between the sexes. These drivers should be closely considered during drug development to enhance acceptability in this population.

Purpose: Medicine acceptability, which is of the utmost importance for vulnerable patients' adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population., Methods: An observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years). Mapping and clustering explored these multiple observational measures and summarised the main information into an intelligible reference framework. Resampling statistics were used to validate the model's reliability., Results: A three-dimensional map and two clusters defining acceptability profiles, as positive or negative, emerged from the 1079 evaluations. Factors of interest (medicines, user features…) were positioned on the map at the barycentre of their evaluations and assigned to an acceptability profile. Focusing on patients' ability to swallow, we have highlighted the tool's efficacy in demonstrating the impact of user features on medicine acceptability., Conclusions: This multivariate approach provides a relevant judgement criterion for this multi-dimensional concept. Facilitating the choice of the most appropriate dosage form to achieve optimal acceptability in a targeted population, this tool is of real potential to improve clinical decisions.

Background: Elderly patients are more susceptible to Clostridium difficile infections (CDIs). Despite existing guidelines, there is no specific treatment for CDI in geriatrics. Vancomycin is commonly used in the treatment of CDI. Teicoplanin is an alternative glycopeptide which recently received marketing authorization approval for CDI in Europe., Objectives: Evaluate the potential interest of oral teicoplanin and assess whether such treatment could potentially become an alternative treatment in mild to severe CDIs in elderly patients., Methods: A prospective monocentric study was conducted over 10 months (from December 2015 to October 2016) in a geriatric unit (Sainte Périne, AP-HP, Paris, France). According to the remote infectious disease specialist, some hospitalized patients suffering from CDI and aged over 65 years received oral teicoplanin 200 mg twice a day (highest dose recommended). The clinical response to teicoplanin and relapses after treatment were evaluated. Patients were monitored up to 90 days after teicoplanin administration, and analyzed in non-responder imputation analysis., Results: Eleven patients received teicoplanin among 19 CDIs during the study time period. In non-responder imputation analysis, 90.9% (n = 10) successfully responded to oral teicoplanin. The rate of relapse observed after a 90-day follow-up was 36.4%. Patients reported no drug-related adverse effects., Conclusion: Oral teicoplanin is a glycopeptide that could be proposed as an alternative to other recommended drugs for CDI. In our case series, teicoplanin seems to be an effective therapy as a first-line regimen for CDI in geriatrics. Such treatment has good acceptability in geriatrics, considering it can be taken orally twice a day.

Objectives: To assess the impact of physician awareness to promote the prescription and the dispensing of generic drugs at hospital discharge., Methods: The study consisted in a Before/After Study design including the analysis of medical prescriptions at hospital discharge, after a pharmaceutical intervention to physicians in a geriatric ward. Each drug was classified according to its terms of prescribing (International Nonproprietary Name (INN), Generic or Trade Name). The primary endpoint defined is the rate of medication prescribed by INN or generic. Statistical analysis was performed on all medicines and according to the prescribers' status (junior/senior)., Results: Three hundred and fifty one drugs were prescribed in the group "before intervention" versus 301 in the group "after". The average number of drugs prescribed per patient was similar between the two groups (9.5 drugs/patient). A generic prescription has been improved by 5% between the two periods (19.7% "before" vs 24.3% "after", p=0.27). Analysis on prescriber status indicates that the pharmaceutical intervention had a significant impact on junior physicians, which resulted in improved prescribing of drug (INN or generic) from 17.6% to 31.4% between the two periods (p=0.006)., Conclusion: The pharmaceutical intervention to physicians has led to an improvement of drug prescription (INN or generic) at hospital discharge. This awareness has affected mainly junior prescribers hence the need to extend this type of intervention to all prescribers of our establishment.

Aims: This study aimed to determine the influence of gene candidates on mycophenolic acid (MPA) response during the first year of renal transplantation., Materials & Methods: A total of 218 renal transplant recipients who received MPA from the first day of transplantation at a fixed dose of 2 g/day were genotyped for ABCB1, ABCC2, UGT2B7, UGT1A9, SLCO1B1, SLCO1B3 and IMPDH1 polymorphisms. Clinical end points were MPA-related adverse drug reactions (ADRs) and acute rejection episodes during the first year post-transplantation., Results: After correction for multiple statistical testing, SLCO1B1 (encoding the hepatic uptake transporter OATP1B1) was the only gene associated with MPA-related ADRs, showing a 75% risk reduction in favor of a protective effect of the SLCO1B1*5 allele (p = 0.002). In vitro experiments showed that MPA metabolites MPA-phenyl-glucuronide and MPA-acyl-glucuronide are substrates of OATP1B1. Their transport was decreased in the presence of the variant transporter (OATP1B1*5)., Conclusion: These results suggest for the first time that carriers of the SLCO1B1*5 allele seem to be protected from MPA-related ADRs.