Five steps to high quality antimicrobial stewardship research.

The escalating threat of antimicrobial resistance (AMR) necessitates impactful, reproducible, and scalable antimicrobial stewardship strategies. This review addresses the critical need to enhance the quality of antimicrobial stewardship intervention research. We propose five considerations for authors planning and evaluating antimicrobial stewardship initiatives. Antimicrobial stewards should consider the following mnemonic ABCDE: (A) plan Ahead using implementation science; (B) Be clear and thoroughly describe the intervention by using the TidIER checklist; (C) Use a Checklist to comprehensively report study components; (D) Select a study Design carefully; and (E) Assess Effectiveness and implementation by selecting meaningful outcomes. Incorporating these recommendations will help strengthen the evidence base of antimicrobial stewardship literature and support optimal implementation of strategies to mitigate AMR.

The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. METHODS: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. RESULTS: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). CONCLUSIONS: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

Association between infectious diseases consultation and mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: Data supporting routine infectious diseases (ID) consultation in Gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. METHODS: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. RESULTS: Of 30,159 patients with GN-BSI across 53 hospitals, 11,013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7-76.1%, interquartile range 19.6-41.1%). 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully-adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted HR 0.82, 95% CI 0.77-0.88, p < 0.0001; translating to absolute risk reduction of -3.8% or NNT of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). CONCLUSIONS: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.

Computational Deconvolution of Cell Type-Specific Gene Expression in COPD and IPF Lungs Reveals Disease Severity Associations.

RATIONALE: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n>1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity. METHODS: We analyzed lung tissue RNA-seq data from 1026 subjects (COPD, n=465; IPF, n=213; control, n=348) from the Lung Tissue Research Consortium. We performed RNA-seq deconvolution, querying thirty-eight discrete cell-type varieties in the lungs. We tested whether deconvoluted cell-type abundance and cell type-specific gene expression were associated with disease severity. RESULTS: The abundance score of twenty cell types significantly differed between IPF and control lungs. In IPF subjects, eleven and nine cell types were significantly associated with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), respectively. Aberrant basaloid cells, a rare cells found in fibrotic lungs, were associated with worse FVC and DLCO in IPF subjects, indicating that this aberrant epithelial population increased with disease severity. Alveolar type 1 and vascular endothelial (VE) capillary A were decreased in COPD lungs compared to controls. An increase in macrophages and classical monocytes was associated with lower DLCO in IPF and COPD subjects. In both diseases, lower non-classical monocytes and VE capillary A cells were associated with increased disease severity. Alveolar type 2 cells and alveolar macrophages had the highest number of genes with cell type-specific differential expression by disease severity in COPD and IPF. In IPF, genes implicated in the pathogenesis of IPF, such as matrix metallopeptidase 7, growth differentiation factor 15, and eph receptor B2, were associated with disease severity in a cell type-specific manner. CONCLUSION: Utilization of RNA-seq deconvolution enabled us to pinpoint cell types present in the lungs that are associated with the severity of COPD and IPF. This knowledge offers valuable insight into the alterations within tissues in more advanced illness, ultimately providing a better understanding of the underlying pathological processes that drive disease progression.

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.

Demographic Representation in Clinical Research Relative to a Cochlear Implant Patient Population.

OBJECTIVES: Research samples that are representative of patient populations are needed to ensure the generalizability of study findings. The primary aim was to assess the efficacy of a study design and recruitment strategy in obtaining a participant sample that was representative of the broader cochlear implant (CI) patient population at the CI center. A secondary aim was to review whether the CI recipient population was representative of the state population. METHODS: Demographic variables were compared for a research participant sample (n = 79) and the CI patient population (n = 338). The participant sample was recruited from the CI patient population. The study design included visits that were at the same location and frequency as the recommended clinical follow-up intervals. The demographics for the combined group (participant sample and patient population) were then compared to the reported demographics for the population in North Carolina. RESULTS: There were no significant differences between the participant sample and patient population for biological sex, age at implantation, racial distribution, socioeconomic position, degree of urbanization, or drive time to the CI center (p ≥ 0.086). The combined CI recipient population was significantly different from the North Carolina population for the distributions of race, ethnicity, and degree of urbanization (p < 0.001). CONCLUSION: The study design and recruitment strategy allowed for recruitment of a participant sample that was representative of the CI patient population. Disparities in access to cochlear implantation persist, as supported by the significant differences in the combined CI recipient population and the population for our state. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Progressive Pulmonary Fibrosis and Interstitial Lung Abnormalities: AJR Expert Panel Narrative Review.

Progressive pulmonary fibrosis (PPF) and interstitial lung abnormalities (ILA) are relatively new concepts in interstitial lung disease (ILD) imaging and clinical management. Recognition of signs of PPF, as well as identification and classification of ILA, are important tasks during chest high-resolution CT interpretation, to optimize management of patients with ILD and those at risk of developing ILD. However, following professional society guidance, the role of imaging surveillance remains unclear in stable patients with ILD, asymptomatic patients with ILA who are at risk of progression, and asymptomatic patients at risk of developing ILD without imaging abnormalities. In this AJR Expert Panel Narrative Review, we summarize the current knowledge regarding PPF and ILA and describe the range of clinical practice with respect to imaging patients with ILD, those with ILA, and those at risk of developing ILD. In addition, we offer suggestions to help guide surveillance imaging in areas with an absence of published guidelines, where such decisions are currently driven primarily by local pulmonologists' preference.

Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. METHODS: Adult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. RESULTS: Thirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0-29.7%; range, 0-66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90-1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16-1.21) and fewer number of days alive and out of hospital at 30 and 90 days. DISCUSSION: FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.

The Toxoplasma monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival.

The apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here, we used TurboID and genome engineering to identify apicoplast transporters in Toxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to have evolved from a putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establish T. gondii parasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexans.

A systematic review of posterior pilon variant fractures.

Posterior pilon variant ankle fractures (PPVF) are a unique subtype of posterior malleolar fractures which have been a source of controversy and confusion in recent years. There has not been a thorough literature review previously written on the topic. Database searches of PubMed and Embase were conducted from inception until June 2023. The key words included "pilon variant," "posterior pilon variant," and "posterior pilon" fractures. Outcomes were evaluated by union time, rates of delayed union, nonunion, malunion, and complication. A total of 15 articles relevant to surgical repair of pilon variant fractures were included in the literature review. The unique mechanism of injury has been reported to involve both rotational and axial forces, leading to involvement of the posterior and medial aspects of the distal tibia. Pilon variant fractures can be suspected by several characteristics on radiographs and have a high confirmation rate via CT images. Multiple systems have been proposed to classify this fracture pattern, but there is no consensus on the ideal classification system. Surgically, direct fixation has shown better short-term clinical outcomes versus indirect fixation or no fixation. PPVF have a distinct fracture pattern involving the posterior and medial columns of the distal tibial plafond, and results from a mechanism intermediate to rotational and axial forces. These fractures are more severe than tri-malleolar fractures due to increased rates of articular impaction and incongruity. Future classification systems should focus on joint surface area and the tibial pilon column involved to avoid confusion with less severe posterior malleolar fractures.

Human Macrophages Activate Bystander Neutrophils' Metabolism and Effector Functions When Challenged with Mycobacterium tuberculosis.

Neutrophils are dynamic cells, playing a critical role in pathogen clearance; however, neutrophil infiltration into the tissue can act as a double-edged sword. They are one of the primary sources of excessive inflammation during infection, which has been observed in many infectious diseases including pneumonia and active tuberculosis (TB). Neutrophil function is influenced by interactions with other immune cells within the inflammatory lung milieu; however, how these interactions affect neutrophil function is unclear. Our study examined the macrophage-neutrophil axis by assessing the effects of conditioned medium (MΦ-CM) from primary human monocyte-derived macrophages (hMDMs) stimulated with LPS or a whole bacterium (Mycobacterium tuberculosis) on neutrophil function. Stimulated hMDM-derived MΦ-CM boosts neutrophil activation, heightening oxidative and glycolytic metabolism, but diminishes migratory potential. These neutrophils exhibit increased ROS production, elevated NET formation, and heightened CXCL8, IL-13, and IL-6 compared to untreated or unstimulated hMDM-treated neutrophils. Collectively, these data show that MΦ-CM from stimulated hMDMs activates neutrophils, bolsters their energetic profile, increase effector and inflammatory functions, and sequester them at sites of infection by decreasing their migratory capacity. These data may aid in the design of novel immunotherapies for severe pneumonia, active tuberculosis and other diseases driven by pathological inflammation mediated by the macrophage-neutrophil axis.

Towards the adoption of quantitative computed tomography in the management of interstitial lung disease.

The shortcomings of qualitative visual assessment have led to the development of computer-based tools to characterise and quantify disease on high-resolution computed tomography (HRCT) in patients with interstitial lung diseases (ILDs). Quantitative CT (QCT) software enables quantification of patterns on HRCT with results that are objective, reproducible, sensitive to change and predictive of disease progression. Applications developed to provide a diagnosis or pattern classification are mainly based on artificial intelligence. Deep learning, which identifies patterns in high-dimensional data and maps them to segmentations or outcomes, can be used to identify the imaging patterns that most accurately predict disease progression. Optimisation of QCT software will require the implementation of protocol standards to generate data of sufficient quality for use in computerised applications and the identification of diagnostic, imaging and physiological features that are robustly associated with mortality for use as anchors in the development of algorithms. Consortia such as the Open Source Imaging Consortium have a key role to play in the collation of imaging and clinical data that can be used to identify digital imaging biomarkers that inform diagnosis, prognosis and response to therapy.

Transkingdom Network Analysis (TkNA): a systems framework for inferring causal factors underlying host-microbiota and other multi-omic interactions.

We present Transkingdom Network Analysis (TkNA), a unique causal-inference analytical framework that offers a holistic view of biological systems by integrating data from multiple cohorts and diverse omics types. TkNA helps to decipher key players and mechanisms governing host-microbiota (or any multi-omic data) interactions in specific conditions or diseases. TkNA reconstructs a network that represents a statistical model capturing the complex relationships between different omics in the biological system. It identifies robust and reproducible patterns of fold change direction and correlation sign across several cohorts to select differential features and their per-group correlations. The framework then uses causality-sensitive metrics, statistical thresholds and topological criteria to determine the final edges forming the transkingdom network. With the subsequent network's topological features, TkNA identifies nodes controlling a given subnetwork or governing communication between kingdoms and/or subnetworks. The computational time for the millions of correlations necessary for network reconstruction in TkNA typically takes only a few minutes, varying with the study design. Unlike most other multi-omics approaches that find only associations, TkNA focuses on establishing causality while accounting for the complex structure of multi-omic data. It achieves this without requiring huge sample sizes. Moreover, the TkNA protocol is user friendly, requiring minimal installation and basic familiarity with Unix. Researchers can access the TkNA software at https://github.com/CAnBioNet/TkNA/ .

Evaluation of an automated feedback intervention to improve antibiotic prescribing among primary care physicians (OPEN Stewardship): a multinational controlled interrupted time-series study.

Tools to advance antimicrobial stewardship in the primary health care setting, where most antimicrobials are prescribed, are urgently needed. The aim of this study was to evaluate OPEN Stewarship (Online Platform for Expanding aNtibiotic Stewardship), an automated feedback intervention, among a cohort of primary care physicians. We performed a controlled, interrupted time-series study of 32 intervention and 725 control participants, consisting of primary care physicians from Ontario, Canada and Southern Israel, from October 2020 to December 2021. Intervention participants received three personalized feedback reports targeting several aspects of antibiotic prescribing. Study outcomes (overall prescribing rate, prescribing rate for viral respiratory conditions, prescribing rate for acute sinusitis, and mean duration of therapy) were evaluated using multilevel regression models. We observed a decrease in the mean duration of antibiotic therapy (IRR = 0.94; 95% CI: 0.90, 0.99) in intervention participants during the intervention period. We did not observe a significant decline in overall antibiotic prescribing (OR = 1.01; 95% CI: 0.94, 1.07), prescribing for viral respiratory conditions (OR = 0.87; 95% CI: 0.73, 1.03), or prescribing for acute sinusitis (OR = 0.85; 95% CI: 0.67, 1.07). In this antimicrobial stewardship intervention among primary care physicians, we observed shorter durations of therapy per antibiotic prescription during the intervention period. The COVID-19 pandemic may have hampered recruitment; a dramatic reduction in antibiotic prescribing rates in the months before our intervention may have made physicians less amenable to further reductions in prescribing, limiting the generalizability of the estimates obtained.IMPORTANCEAntibiotic overprescribing contributes to antibiotic resistance, a major threat to our ability to treat infections. We developed the OPEN Stewardship (Online Platform for Expanding aNtibiotic Stewardship) platform to provide automated feedback on antibiotic prescribing in primary care, where most antibiotics for human use are prescribed but where the resources to improve antibiotic prescribing are limited. We evaluated the platform among a cohort of primary care physicians from Ontario, Canada and Southern Israel from October 2020 to December 2021. The results showed that physicians who received personalized feedback reports prescribed shorter courses of antibiotics compared to controls, although they did not write fewer antibiotic prescriptions. While the COVID-19 pandemic presented logistical and analytical challenges, our study suggests that our intervention meaningfully improved an important aspect of antibiotic prescribing. The OPEN Stewardship platform stands as an automated, scalable intervention for improving antibiotic prescribing in primary care, where needs are diverse and technical capacity is limited.

Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of C. asiatica Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-ß Toxicity.

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of Centella asiatica (C. asiatica) that protect against Aß cytotoxicity in vitro. C. asiatica has been associated with improving mental health and cognitive function, with potential use in Alzheimer's disease. Human neuroblastoma MC65 cells were exposed to subfractions of an aqueous extract of C. asiatica to evaluate the protective benefit derived from these subfractions against amyloid ß-cytotoxicity. The % viability score of the cells exposed to each subfraction was used in conjunction with the intensity of the molecular features in two computational models, namely Elastic Net and selectivity ratio, to determine the relationship of the peak intensity of molecular features with % viability. Finally, the correlation of mass spectral features with MC65 protection and their abundance in different sub-fractions were visualized using GNPS molecular networking. Both computational methods unequivocally identified dicaffeoylquinic acids as providing strong protection against Aß-toxicity in MC65 cells, in agreement with the protective effects observed for these compounds in previous preclinical model studies.

Factors that influence performance in pediatric cochlear implant recipients with cochlear nerve deficiency.

OBJECTIVES: Children with cochlear nerve deficiency (CND) have wide variability in outcomes with cochlear implant (CI) use. The current study aims to report a large cohort of pediatric CI recipients with CND and to evaluate for factors that may predict improved performance. METHODS: The current study is a retrospective review of pediatric CI recipients with CND at a tertiary academic hospital. Variables including cochlear nerve status (hypoplasia vs aplasia), age at implantation, cochleovestibular malformation, bony cochlear nerve aperture, internal auditory canal aperture, and cognitive delay were evaluated for predictors of postoperative performance. A stepwise multinomial regression analysis was performed. RESULTS: Forty-seven CI recipients (54 ears) were included in the analysis. A majority (59%) showed auditory capabilities with their CI. Twenty percent of recipients achieved some level of open-set speech perception with their CI. The regression analysis identified cochlear nerve status and cognitive delay as predictors of performance. CI recipients with cochlear nerve hypoplasia had significantly improved performance compared to those with aplasia (p = 0.003). Recipients with cognitive delay had more limited benefit than those without cognitive delay (p = 0.033). CONCLUSIONS: Children with CND can benefit from CI use, with outcomes spanning from non-use to development of spoken language. Predictive factors for improved performance include a lack of cognitive delay and cochlear hypoplasia rather than aplasia. These can be important considerations for parent counseling and decision making.

From the operating table to global science: How a near-death experience sparked my passion for life.

Kevin Christopher Brown Jr. is a winner of the fourth annual Rising Black Scientists Awards for a scholar in the life and health sciences. We asked emerging Black scientists to tell us about their scientific vision and goals, experiences that sparked their interest in science, how they want to contribute to a more inclusive scientific community, and how these all fit together on their journey. This is his story.

AIDSImpact special issue: factors associated with PrEP use in a community sample of African American men who have sex with men (MSM) and transgender women (TGW) in the United States Midwest.

Black sexual minority men who have sex with men (MSM) in the United States are at disparate risk for contracting HIV infection, but pre-exposure prophylaxis (PrEP) use is suboptimal. Social network methods were used to recruit a community sample of racial minority MSM and transgender women (TGW) in two Midwestern US cities. 250 PrEP-eligible (HIV-negative) participants completed measures assessing current and intended PrEP use; demographic characteristics; PrEP knowledge, attitudes, norms, stigma, and self-efficacy; and structural barriers to PrEP. Multivariate analyses established predictors of current and intended PrEP use. Only 12% of participants reported currently using PrEP, which was associated with greater PrEP knowledge and not having a main partner, with trends for greater PrEP use by younger participants and those with partners living with HIV. Among participants not currently on PrEP, strength of PrEP use intentions was associated with higher PrEP knowledge, PrEP descriptive social norms, and PrEP use self-efficacy. This study is among few to directly compare Black who have adopted PrEP with those who have not. Its findings underscore the potential benefits of employing social network approaches for strengthening PrEP use peer norms, increasing PrEP knowledge and self-efficacy, and optimizing PrEP uptake among racial minority MSM and TGW.

Documenting the indication for antimicrobial prescribing: A retrospective observational study of long-term care homes.

BACKGROUND: Overuse of antimicrobials in residents of long-term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long-term care (LTC) homes setting to improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility-level variability of antibiotic indication documentation in this setting. METHODS: This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1, 2021 and December 31, 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level. RESULTS: Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range [IQR]: 10.8%-31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%-42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits. CONCLUSIONS: There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications.