Exposure to doxycycline increases risk of carrying a broad range of enteric antimicrobial resistance determinants in an elderly cohort.

OBJECTIVES: High rates of antibiotic prescription in residential aged care are likely to promote enteric carriage of antibiotic-resistant pathogens and increase the risk of antibiotic treatment failure. Despite their importance, relationships between antibiotic exposures and patterns of enteric resistance carriage in this population remain poorly understood. METHODS: We conducted a cross-sectional metagenomic cohort analysis of stool samples from residents of five long-term aged-care facilities in South Australia. Taxonomic composition was determined, and enteric carriage of antibiotic resistance genes (ARGs) was identified and quantified against the Comprehensive Antibiotic Resistance Database. Both the detection and abundance of stool taxa and ARGs were related to antibiotic exposures up to 12 months prior. Factors associated with the abundance of ARGs of high clinical concern were identified. RESULTS: Stool samples were provided by 164 participants (median age: 88 years, IQR 81-93; 72% female). Sixty-one percent (n = 100) of participants were prescribed antibiotics at least once in the prior 12 months (median prescriptions: 4, range: 1-52), most commonly a penicillin (n = 55, 33.5%), cephalosporin (n = 53, 32.3%), diaminopyrimidine (trimethoprim) (n = 36, 22%), or tetracycline (doxycycline) (n = 21, 12.8%). More than 1100 unique ARGs, conferring resistance to 38 antibiotic classes, were identified, including 20 ARGs of high clinical concern. Multivariate logistic regression showed doxycycline exposure to be the greatest risk factor for high ARG abundance (adjusted odds ratio [aOR]=14.8, q<0.001) and a significant contributor to inter-class selection, particularly for ARGs relating to penicillins (aOR=3.1, q=0.0004) and cephalosporins (aOR=3.4, q=0.003). High enteric ARG abundance was associated with the number of separate antibiotic exposures (aOR: 6.4, q<0.001), exposures within the prior 30 days (aOR: 4.6, q=0.008) and prior 30-100 days (aOR: 2.6, q=0.008), high duration of antibiotic exposure (aOR: 7.9, q<0.001), and exposure to 3 or more antibiotic classes (aOR: 7.4, q<0.001). Carriage of one or more ARGs of high clinical concern was identified in 99% of participants (n = 162, median: 3, IQR: 2-4), involving 11 ARGs conferring resistance to aminoglycosides, four to beta-lactams, one to glycopeptides, three to fluoroquinolones, and one to oxazolidinones. Carriage of ARGs of high clinical concern was positively associated with exposure to doxycycline (aminoglycoside, fluoroquinolone, and oxazolidinone ARGs) and trimethoprim (fluoroquinolone and beta-lactam ARGs). Analysis of doxycycline impact on microbiota composition suggested that observed resistome changes arose principally through direct ARG selection, rather than through the antibiotic depletion of sensitive bacterial populations. CONCLUSIONS: The gut microbiome of aged care residents is a major reservoir of antibiotic resistance. As a critical antibiotic in medical practice, a comprehensive understanding of the impact of doxycycline exposure on the gut resistome is paramount for informed antibiotic use, particularly in an evolving landscape of prophylactic applications. Near-universal asymptomatic carriage of clinically critical resistance determinants is highly concerning and reinforces the urgent need for improved management of antibiotic use in long-term aged care.

Screening and treatment of anxiety symptoms within an interdisciplinary comprehensive epilepsy center.

Youth with epilepsy (YWE) are at elevated risk for anxiety, yet anxiety is often undetected and understudied in this population. Most research on anxiety in YWE is based on parent proxy-report and broad-band measures with limited sensitivity. The aim of the current study was to: 1) examine rates of anxiety symptoms in YWE using a diagnosis-specific, self-report measure of anxiety symptoms, 2) assess differences in anxiety symptoms by sociodemographic and medical variables, and 3) evaluate changes in anxiety symptoms following a brief behavioral health intervention delivered within an interdisciplinary epilepsy clinic visit. As part of routine clinical care, 317 YWE [Mage=13.4+2.5 years (range 7-19 years); 54% female; 84% White: Non-Hispanic] completed the Multidimensional Anxiety Scale for Children, self-report (MASC-10), with a subset completing the MASC-10 at a second timepoint (n=139). A retrospective chart review was completed and sociodemographic, medical variables and behavioral health interventions were collected. Thirty percent of YWE endorsed elevated anxiety symptoms, with higher rates in those who were younger. YWE who received a behavioral health intervention for anxiety (n=21) demonstrated greater decreases in anxiety symptoms from Time 1 to Time 2 compared to those who did not receive a behavioral intervention (n=108). The integration of psychologists into pediatric epilepsy clinics may have allowed for early identification of anxiety symptoms, as well behavioral interventions to address these symptoms, which has the potential to decrease the need for more intensive services.

The development and validation of the One Health Community Assessment.

Interdisciplinary collaborations to address human, animal, and environmental health have been emphasized since the inception of the One Health framework. A quantitative survey instrument was developed to measure perceptions of the impacts of pets on One Health. Using the exploratory sequential mixed methods approach, 20 interviews were conducted with individuals from a racially diverse and low-socioeconomic status community in the U.S. to understand their perceptions of One Health. Data from those interviews informed the development of a Likert scale survey measuring individual perceptions of community, human, pet, and environmental health and welfare, as well as the connections between the domains of the One Health triad (human, animal, and environment). The resulting One Health Community Assessment (OHCA) was administered in two urban and two rural underserved U.S. communities longitudinally (2018-2021) through door-to-door data collection as well as phone, email, and text surveys. Validation of the instrument was completed using data collected in the third and fourth years of the study (n = 654). Factor analysis with orthogonal varimax rotation was used to assess the structure and internal consistency of the OHCA. Five subscales explained 42.4% of the variance in our 92-item instrument: community health (Cronbach's α = 0.897), human health (α = 0.842), pet health (α = 0.899), environmental health (α = 0.789), and connections between domains of One Health (α = 0.762). The OHCA represents the first reliable and validated instrument to measure the impacts of pets on One Health.

Patient and healthcare provider perceptions of acceptability of fingerstick point-of-care hepatitis C testing at Aboriginal Community Controlled Health Services in Australia.

BACKGROUND: Hepatitis C (HCV) is highly prevalent in First Nations communities globally. Barriers in the uptake of testing and treatment create challenges to realise elimination of HCV in these communities. In efforts to reduce barriers to testing and treatment, the SCALE-C study implemented an HCV test-and-treat intervention integrating point-of-care HCV testing and FibroScan®. SCALE-C was carried out at four Aboriginal Community Controlled Health Services (ACCHS; renowned for providing culturally safe care) in four regional towns in Australia. This qualitative analysis sought to understand healthcare provider and patient perceptions of acceptability of a community-based HCV test-and-treat intervention within ACCHS. METHODS: Semi-structured interviews were undertaken with 23 patient participants and 14 healthcare personnel (including Aboriginal Health Workers/Practitioners, nurses, general practitioners, and practice managers) from across the four ACCHS involved in SCALE-C. A coding framework was developed among study authors and informed by Sekhon's Theoretical Framework of Acceptability. RESULTS: The SCALE-C intervention enabled opportunities for healthcare providers to listen to patients, and for patients to feel heard (affective attitude). HCV testing was opportunistic and often occurred outside of the allocated SCALE-C clinical hours (burden). For patients, HCV testing within SCALE-C was viewed as a moral responsibility and ensured protection of self and others (ethicality). For personnel, SCALE-C (including following up visits) was regarded as an opportunity to engage with patients especially those with complex health needs which may be unrelated to HCV risk factors (ethicality). Patients and personnel widely regarded the SCALE-C intervention to be effective, and the test-and-treat model was preferable for both patients and personnel. CONCLUSION: The SCALE-C intervention was broadly perceived to be acceptable among both healthcare providers and patients within ACCHS. Whilst the prioritisation of HCV was viewed as increasing patient engagement, it was also regarded as an opportunity for addressing other healthcare needs within Aboriginal communities. HCV test-and-treat models of care delivered by ACCHS simplify the HCV care pathway and ensure all HCV care is provided in a culturally safe setting (e.g., patients did not need to attend external services such as pathology).

Distinctive Optical Coherence Tomography Angiography and Indocyanine Green Angiography Imaging Patterns in Topiramate-Induced Choroidal Effusion.

PURPOSE: To describe novel findings seen on optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) in a young male patient presenting with bilateral topiramate-induced choroidal effusion. METHODS: Retrospective case report. A comprehensive ophthalmic examination was conducted and multimodal imaging techniques, including B-scan ultrasound, OCT, OCTA, and ICGA were analyzed. RESULTS: A male in his 30s presented with a myopic shift due to bilateral choroidal effusion induced by a medication containing topiramate prescribed for weight loss. ICGA showed multiple hypofluorescent spots within the choroid corresponding to areas of reduced OCTA flow signal in both the inner and deeper en face choroidal slabs. Symptoms and abnormal imaging findings resolved within five days of discontinuing the medication. CONCLUSION: Findings observed with OCTA and ICGA together suggest multifocal reversible areas of reduced choroidal vascular flow occurring in a topiramate-induced choroidal effusion. We propose that this transient hypoperfusion is due to compression from deeper choroidal vessels with a congested choroid.

A Trainee-Led Quality Improvement Project Using Change Management Theory to Improve Bedside Rounding.

OBJECTIVE: The coronavirus disease 2019 pandemic disrupted the practice of family-centered rounds. After the height of the pandemic, a trainee-led team identified a low percentage of bedside rounds on general pediatrics resident teams and combined a quality improvement framework and change management theory to increase bedside rounds. Initial efforts focused on a single general pediatrics team with the aim to increase bedside rounds from 18% to 50% within 6 months and sustain improvement for 12 months. A second aim was to increase bedside rounds from 7% to 50% for all general pediatrics resident teams within 6 months of spread. METHODS: The Model for Improvement informed the identification of 3 primary drivers of bedside rounds: knowledge, culture, and logistics. Twelve plan-do-study-act (PDSA) cycles were implemented. Measures included the percentage of bedside rounds (primary outcome), caregiver attendance (secondary outcome), and nurse attendance and rounding time (balancing measures). RESULTS: For the initial team, 13 522 patient days were analyzed for the primary outcome with the average percentage of weekly bedside rounds increasing from 18% to 89% with 12 months of sustained improvement. The spread of the intervention to all teams revealed an increase in bedside rounding from 7% to 54%. The most significant improvements occurred after PDSA cycle 2, a communication bundle, and PDSA cycle 5, when the project was spread to all teams. CONCLUSIONS: This trainee-led initiative reveals the strength of the incorporation of change management theory within a quality improvement framework, resulting in rapid and sustainable increase in bedside rounds.

Cohort profile: GRACE - a residential aged care cohort examining factors influencing antimicrobial resistance carriage.

BACKGROUND: The emergence of antimicrobial-resistant bacteria represents a considerable threat to human health, particularly for vulnerable populations such as those living in residential aged care. However, antimicrobial resistance carriage and modes of transmission remain incompletely understood. The Generating evidence on antimicrobial Resistance in the Aged Care Environment (GRACE) study was established to determine principal risk factors of antimicrobial resistance carriage and transmission in residential aged care facilities (RACFs). This article describes the cohort characteristics, national representation, and planned analyses for this study. METHODS: Between March 2019 and March 2020, 279 participants were recruited from five South Australian RACFs. The median age was 88.6 years, the median period in residence was 681 days, and 71.7% were female. A dementia diagnosis was recorded in 54.5% and more than two thirds had moderate to severe cognitive impairment (68.8%). 61% had received at least one course of antibiotics in the 12 months prior to enrolment. RESULTS: To investigate the representation of the GRACE cohort to Australians in residential aged care, its characteristics were compared to a subset of the historical cohort of the Registry of Senior Australians (ROSA). This included 142,923 individuals who were permanent residents of RACFs on June 30th, 2017. GRACE and ROSA cohorts were similar in age, sex, and duration of residential care, prevalence of health conditions, and recorded dementia diagnoses. Differences were observed in care requirements and antibiotic exposure (both higher for GRACE participants). GRACE participants had fewer hospital visits compared to the ROSA cohort, and a smaller proportion were prescribed psycholeptic medications. CONCLUSIONS: We have assembled a cohort of aged care residents that is representative of the Australian aged care population, and which provides a basis for future analyses. Metagenomic data isolated from participants and built environments will be used to determine microbiome and resistome characteristics of an individual and the facility. Individual and facility risk exposures will be aligned with metagenomic data to identify principal determinants for antimicrobial resistance carriage. Ultimately, this analysis will inform measures aimed at reducing the emergence and spread of antimicrobial resistant pathogens in this high-risk population.

Preventing empirical antibiotic treatment failure in migrant populations: screening by infection risk, not ethnic background.

Multidrug-resistant organisms (MDROs) are a major international health threat. In many low and middle-income countries poorly regulated antibiotic use, limited surveillance, and inadequate sanitation give rise to high rates of antibiotic resistance. A resulting reliance on last-line antibiotic options further contributes to the emergence of MDROs. The potential for these pathogens to spread across international borders is a matter of considerable concern. However, this problem is commonly framed as primarily a threat to the health security of countries where resistance is not yet endemic. In fact, it is little acknowledged that those at greatest risk from antibiotic treatment failure are individuals who move from regions of high MDRO prevalence to settings where standard empirical treatment options remain largely effective. In this perspective, we highlight the poor treatment outcomes for disseminated bacterial infections in individuals who have moved from settings in which MDROs are common to those where MDROs are currently less common. We discuss MDRO screening strategies that could avoid stigmatizing vulnerable populations by focusing on future risk of disseminated infection, rather than past risk of acquisition. In practical terms, this means screening individuals before childbirth, immunosuppressive treatments, major surgery, or other events associated with disseminated infection risk, rather than prioritizing screening for individuals from regions with high carriage rates. We argue that such measures would reduce antibiotic treatment failure and improve outcomes while protecting migrant populations from the divisive consequences of targeted screening programs.

Cash Transfer Programs for Child Health-Elucidating Pathways and Optimizing Program Design.

This Viewpoint describes how nondirected cash transfer programs influence the dynamics of child poverty, highlights pathways by which poverty reduction programs could improve child health, and provides suggested directions for future research and policy.