Empirical antibiotic therapy modalities for Enterobacteriaceae bloodstream infections in older patients and their impact on mortality: a multicentre retrospective study.

PURPOSE: Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival. METHODS: This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression. RESULTS: Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality. CONCLUSION: While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality.

The Mortality of Infective endocarditis with and without Surgery in Elderly (MoISE) Study.

BACKGROUND: Infective endocarditis (IE) is increasingly affecting older patients. However, data on their management are sparse, and the benefits of surgery in this population are unclear. METHODS: We included patients with left-sided IE (LSIE) aged ≥ 80 years enrolled in a prospective endocarditis cohort managed in Aquitaine, France, from 2013 to 2020. Geriatric data were collected retrospectively to identify factors associated with the 1-year risk of death using Cox regression. RESULTS: We included 163 patients with LSIE (median age, 84 years; men, 59%; rate of prosthetic LSIE, 45%). Of the 105 (64%) patients with potential surgical indications, 38 (36%) underwent valve surgery: they were younger, more likely to be men with aortic involvement, and had a lower Charlson comorbidity index. Moreover, they had better functional status at admission (ie, the ability to walk unassisted and a higher median activities of daily living [ADL] score; n = 5/6 vs 3/6, P = .01). The 1-year mortality rate in LSIE patients without surgical indications was 28%; it was lower in those who were operated on compared with those who were not despite a surgical indication (16% vs 66%, P < .001). Impaired functional status at admission was strongly associated with mortality regardless of surgical status. In patients unable to walk unassisted or with an ADL score <4, there was no significant surgical benefit for 1-year mortality. CONCLUSIONS: Surgery improves the prognosis of older patients with LSIE and good functional status. Surgical futility should be discussed in patients with altered autonomy. The endocarditis team should include a geriatric specialist.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin 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 FINDINGS: This 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 <3 months, vitamin D supplementation >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. CONCLUSIONS: In 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 REGISTRATION: ClinicalTrials.gov NCT04344041.

Infectious diseases and cognition: do we have to worry?

OBJECTIVES: 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. METHODS: 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. RESULTS/ CONCLUSIONS: 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.

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

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.

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

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.

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

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.

Review: Helicobacter pylori and extragastric diseases.

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.

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

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 [19­104] 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.

Association between Helicobacter pylori infection and incident risk of dementia: The AMI cohort.

BACKGROUND: Chronic infectious diseases are increasingly being considered as potential contributors to dementia risk. Among those infections, Helicobacter pylori, the main cause of chronic gastritis worldwide, has been suggested. As the prevalence of H. pylori infection has decreased, the main objective of this work was to reconsider the association between H. pylori infection and the risk of incident dementia, including Alzheimer's disease. METHODS: Prospective cohort of 689 older (≥65 years) agricultural workers from Southwest France. Descriptive and comparative analyses were performed according to H. pylori status determined by serology at baseline. The risk of incident dementia according to H. pylori status over a 7-year follow-up was explored by survival analyses: Kaplan-Meier curve and Cox proportional hazards models. RESULTS: Two-hundred (29.0%) participants were H. pylori-positive at baseline. Compared to H. pylori-negative participants, they showed worse cognitive performances at baseline. Eighty-five incident dementia cases were diagnosed during the follow-up period. After adjustment for age, sex, education, apolipoprotein ε4, and several cardiovascular risk factors, H. pylori remained associated with an increased risk of dementia (HR 1.70, 95% CI, 1.05-2.74). The risk was stronger for Alzheimer's disease (HR 2.85, 95% CI, 1.58-5.12). CONCLUSIONS: Despite an observed decrease in H. pylori infection prevalence, this study provides evidence for the association between H. pylori infection and dementia. These results should encourage further research on the mechanisms underlying the contribution of infectious diseases to pathological brain aging, especially the influence of gut inflammation on the brain.

One Hundred Explicit Definitions of Potentially Inappropriate Prescriptions of Antibiotics in Hospitalized Older Patients: The Results of an Expert Consensus Study.

BACKGROUND: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. OBJECTIVE: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. METHODS: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey's rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. RESULTS: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). CONCLUSIONS: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics.

Extragastric diseases and Helicobacter pylori.

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.

Campylobacter fetus foodborne illness outbreak in the elderly.

In June 2021, a cluster of seven cases of Campylobacter fetus infections occurred in a rehabilitation center and caused significant morbidity in elderly patients including five with bacteremia and two with osteoarticular medical device infections. The genetic identity identified by whole genome sequencing of the different Campylobacter fetus strains confirms a common source. This foodborne illness outbreak may have resulted from the consumption of unpasteurized dairy products, such as a cow's raw milk cheese resulting from a farm-to-fork strategy.

International Consensus Recommendation Guidelines for Subcutaneous Infusions of Hydration and Medication in Adults: An e-Delphi Consensus Study.

Infusion of fluids and medications is traditionally performed intravenously. However, venous depletion in patients has led to the quest for vessel health preservation. A safe, effective, acceptable, and efficient alternative is the subcutaneous route. A lack of organizational policies may contribute to the slow uptake of this practice. This modified e-Delphi (electronic) study aimed to derive international consensus on practice recommendations for subcutaneous infusions of fluids and medications. A panel of 11 international clinicians, with expertise in subcutaneous infusion research and/or clinical practice, rated and edited subcutaneous infusion practice recommendations from evidence, clinical practice guidelines, and clinical expertise within an Assessment, Best Practice, and Competency (ABC) domain guideline model. The ABC Model for Subcutaneous Infusion Therapy provides a systematic guideline of 42 practice recommendations for the safe delivery of subcutaneous infusions of fluids and medications in the adult population in all care settings. These consensus recommendations provide a guideline for health care providers, organizations, and policy makers to optimize use of the subcutaneous access route.

Structured Pre-Consultation Interview at the First Call of Caregiver Regarding Memory Consultation: Effects on Caregiver Burden, Expectations, and Quality of Life.

Introduction: Case managers can guide caregivers during their search for care for relatives with neurocognitive disorders. The present study aimed to evaluate the effects of this procedure on caregiver burden and quality of life. Methods: Family caregivers searching for care at a memory clinic before the first consultation were provided written information and they provided verbal consent to participate in this pre-post intervention study. Intervention was a structured pre-consultation phone call interview given by the case manager to inform and organize individualize pathway of care. The mini-Zarit Burden Interview and the EuroQol five-dimensional questionnaire quality of life scores were recorded by an independent assessor before the intervention and 1 month thereafter. An expectation questionnaire was also completed during the assessments. The pre and post scores were compared using the Wilcoxon signed-rank test. Results: In total, 45 participants were enrolled and 35 were assessed twice. There was no significant change in the total mini-Zarit Burden Interview score; however, the levels of stress due to caring and meeting familial responsibilities (p = 0.025), and the fear of what the future holds for the participants' relative (p = 0.01) was lower at 1 month. The need for information about the pathways of care decreased, but no change in support satisfaction was observed. Quality of life was good and did not change. Conclusions: During the pre-consultation intervention, the case manager may fulfill several needs of caregivers, particularly to obtain personalized information, which should be implemented in memory clinics.

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

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.

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

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.

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

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.