Drivers of inappropriate use of antimicrobials in South Asia: A systematic review of qualitative literature.

Antimicrobial resistance is a global public health crisis. Effective antimicrobial stewardship requires an understanding of the factors and context that contribute to inappropriate use of antimicrobials. The goal of this qualitative systematic review was to synthesize themes across levels of the social ecological framework that drive inappropriate use of antimicrobials in South Asia. In September 2023, we conducted a systematic search using the electronic databases PubMed and Embase. Search terms, identified a priori, were related to research methods, topic, and geographic location. We identified 165 articles from the initial search and 8 upon reference review (n = 173); after removing duplicates and preprints (n = 12) and excluding those that did not meet eligibility criteria (n = 115), 46 articles were included in the review. We assessed methodological quality using the qualitative Critical Appraisal Skills Program checklist. The studies represented 6 countries in South Asia, and included data from patients, health care providers, community members, and policy makers. For each manuscript, we wrote a summary memo to extract the factors that impede antimicrobial stewardship. We coded memos using NVivo software; codes were organized by levels of the social ecological framework. Barriers were identified at multiple levels including the patient (self-treatment with antimicrobials; perceived value of antimicrobials), the provider (antimicrobials as a universal therapy; gaps in knowledge and skills; financial or reputational incentives), the clinical setting (lack of resources; poor regulation of the facility), the community (access to formal health care; informal drug vendors; social norms), and policy (absence of a regulatory framework; poor implementation of existing policies). This study is the first to succinctly identify a range of norms, behaviors, and policy contexts driving inappropriate use of antimicrobials in South Asia, emphasizing the importance of working across multiple sectors to design and implement approaches specific to the region.

Heterotopic bone formation in a case of clear cell renal cell carcinoma: A case report.

Renal cell carcinoma (RCC) with heterotopic formation has been reported very rarely. We report this rare entity in a 33-year-old female patient who came to the out-patient department after complaining of pain in the lumbar region of the left side for 2 years. A computed tomography scan showed a heterogeneously enhancing lesion originating from the posterior cortex of the left kidney in the upper pole. It had many chunky calcification foci and was treated with left robotic partial nephrectomy. Histo-pathological examination revealed clear cell RCC with the heterotopic bone formation with a tumor size measuring 5 × 4 × 2.5 cm; the tumor was limited to the kidney, and the tumor resection margin were free of tumor, WHO/ISUP Grade 2. The pathological stage (AJCC 8th edition PTNM) was p T1b p NX p MX. The prognostic implications regarding calcification are poorly addressed in the literature. Patients suffering from osseous metaplasia are often in their early stages of the disease and have a favorable prognosis.

Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4+ T-cell count nadir (p < 0.001), lower serum globulins (p = 0.003), and lower CSF leukocytes (p < 0.001). Without ART, one in 13 PWH had persistently undetectable CSF HIV RNA, while persistent CSF/plasma discordance was extremely rare over years. Immune responses, inflammation, BBB permeability, and iron and lipid metabolism were all associated with HIV replication in CSF.

Inappropriate Diagnosis of Pneumonia Among Hospitalized Adults.

Importance: Little is known about incidence of, risk factors for, and harms associated with inappropriate diagnosis of community-acquired pneumonia (CAP). Objective: To characterize inappropriate diagnosis of CAP in hospitalized patients. Design, Setting, and Participants: This prospective cohort study, including medical record review and patient telephone calls, took place across 48 Michigan hospitals. Trained abstractors retrospectively assessed hospitalized patients treated for CAP between July 1, 2017, and March 31, 2020. Patients were eligible for inclusion if they were adults admitted to general care with a discharge diagnostic code of pneumonia who received antibiotics on day 1 or 2 of hospitalization. Data were analyzed from February to December 2023. Main Outcomes and Measures: Inappropriate diagnosis of CAP was defined using a National Quality Forum-endorsed metric as CAP-directed antibiotic therapy in patients with fewer than 2 signs or symptoms of CAP or negative chest imaging. Risk factors for inappropriate diagnosis were assessed and, for those inappropriately diagnosed, 30-day composite outcomes (mortality, readmission, emergency department visit, Clostridioides difficile infection, and antibiotic-associated adverse events) were documented and stratified by full course (>3 days) vs brief (≤3 days) antibiotic treatment using generalized estimating equation models adjusting for confounders and propensity for treatment. Results: Of the 17 290 hospitalized patients treated for CAP, 2079 (12.0%) met criteria for inappropriate diagnosis (median [IQR] age, 71.8 [60.1-82.8] years; 1045 [50.3%] female), of whom 1821 (87.6%) received full antibiotic courses. Compared with patients with CAP, patients inappropriately diagnosed were older (adjusted odds ratio [AOR], 1.08; 95% CI, 1.05-1.11 per decade) and more likely to have dementia (AOR, 1.79; 95% CI, 1.55-2.08) or altered mental status on presentation (AOR, 1.75; 95% CI, 1.39-2.19). Among those inappropriately diagnosed, 30-day composite outcomes for full vs brief treatment did not differ (25.8% vs 25.6%; AOR, 0.98; 95% CI, 0.79-1.23). Full vs brief duration of antibiotic treatment among patients was associated with antibiotic-associated adverse events (31 of 1821 [2.1%] vs 1 of 258 [0.4%]; P = .03). Conclusions and Relevance: In this cohort study, inappropriate diagnosis of CAP among hospitalized adults was common, particularly among older adults, those with dementia, and those presenting with altered mental status. Full-course antibiotic treatment of those inappropriately diagnosed with CAP may be harmful.

Hypersensitivity reactions following vein closure therapy with venasealTM (n-butyl- 2-cyanoacrylate).

VenaSealTM is composed of a cyanoacrylate adhesive compound often utilized for chronic venous stasis treatment. Rare case reports of hypersensitivity reactions to this compound exist. We present the first case of dermatographism and angioedema after utilization of VenaSealTM successfully treated via high dose antihistamines. We also present a case of type IV hypersensitivity to VenaSealTM, a cyanoacrylate, occurring in a patient with known meth(acrylate) allergy indicating a possible cross reactivity between these acrylate groups.

Engineering self-propelled tumor-infiltrating CAR T cells using synthetic velocity receptors.

Chimeric antigen receptor (CAR) T cells express antigen-specific synthetic receptors, which upon binding to cancer cells, elicit T cell anti-tumor responses. CAR T cell therapy has enjoyed success in the clinic for hematological cancer indications, giving rise to decade-long remissions in some cases. However, CAR T therapy for patients with solid tumors has not seen similar success. Solid tumors constitute 90% of adult human cancers, representing an enormous unmet clinical need. Current approaches do not solve the central problem of limited ability of therapeutic cells to migrate through the stromal matrix. We discover that T cells at low and high density display low- and high-migration phenotypes, respectively. The highly migratory phenotype is mediated by a paracrine pathway from a group of self-produced cytokines that include IL5, TNFα, IFNγ, and IL8. We exploit this finding to "lock-in" a highly migratory phenotype by developing and expressing receptors, which we call velocity receptors (VRs). VRs target these cytokines and signal through these cytokines' cognate receptors to increase T cell motility and infiltrate lung, ovarian, and pancreatic tumors in large numbers and at doses for which control CAR T cells remain confined to the tumor periphery. In contrast to CAR therapy alone, VR-CAR T cells significantly attenuate tumor growth and extend overall survival. This work suggests that approaches to the design of immune cell receptors that focus on migration signaling will help current and future CAR cellular therapies to infiltrate deep into solid tumors.

Antimicrobial Stewardship Teams in Veterans Affairs and Nonfederal Hospitals in the United States: A National Survey of Antimicrobial Stewardship Practices.

In a cross-sectional survey of US acute care hospitals, antimicrobial stewardship programs were present in most Veterans Affairs and nonfederal hospitals but varied in team composition, scope, and impact. Diagnostic stewardship was common across hospitals. Veterans Affairs hospitals had increased reach in outpatient settings. Telestewardship remains an opportunity in all hospital systems.

The next frontier of healthcare-associated infection (HAI) surveillance metrics: Beyond device-associated infections.

In recent years, it has become increasingly evident that surveillance metrics for invasive device-associated infections (ie, central-line-associated bloodstream infections, ventilator-associated pneumonias, and catheter-associated urinary tract infections) do not capture all harms; they capture only a subset of healthcare-associated infections (HAIs). Although prevention of device-associated infections remains critical, we need to address the full spectrum of potential harms from device use and non-device-associated infections. These include complications associated with additional devices, such as peripheral venous and arterial catheters, non-device-associated infections such as nonventilator hospital-acquired pneumonia, and noninfectious device complications such as trauma, thrombosis, and acute lung injury. As authors of the device-associated infection sections in the SHEA/IDSA/APIC Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals, we highlight catheter-associated urinary tract infection as an example of the strengths and limitations of the current emphasis on device-associated infection surveillance, suggest performance metrics that present a more comprehensive picture of patient harm, and provide a high-level overview of similar issues with other infection surveillance measures.

Transition to Oral Antibiotic Therapy for Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Management of gram-negative bloodstream infections (GN-BSIs) with oral antibiotics is highly variable. Objective: To examine the transition from intravenous (IV) to oral antibiotics, including selection, timing, and associated clinical and microbial characteristics, among hospitalized patients with GN-BSIs. Design, Setting, and Participants: A retrospective cohort study was conducted of 4581 hospitalized adults with GN-BSIs at 24 US hospitals between January 1 and December 31, 2019. Patients were excluded if they died within 72 hours. Patients were excluded from the oral therapy group if transition occurred after day 7. Statistical analysis was conducted from July 2022 to October 2023. Exposures: Administration of antibiotics for GN-BSIs. Main Outcomes and Measures: Baseline characteristics and clinical parameters reflecting severity of illness were evaluated in groups receiving oral and IV therapy. The prevalence of transition from IV to oral antibiotics by day 7, median day of transition, sources of infection, and oral antibiotic selection were assessed. Results: Of a total of 4581 episodes with GN-BSIs (median age, 67 years [IQR, 55-77 years]; 2389 men [52.2%]), 1969 patients (43.0%) receiving IV antibiotics were transitioned to oral antibiotics by day 7. Patients maintained on IV therapy were more likely than those transitioned to oral therapy to be immunosuppressed (833 of 2612 [31.9%] vs 485 of 1969 [24.6%]; P < .001), require intensive care unit admission (1033 of 2612 [39.5%] vs 334 of 1969 [17.0%]; P < .001), have fever or hypotension as of day 5 (423 of 2612 [16.2%] vs 49 of 1969 [2.5%]; P < .001), require kidney replacement therapy (280 of 2612 [10.7%] vs 63 of 1969 [3.2%]; P < .001), and less likely to have source control within 7 days (1852 of 2612 [70.9%] vs 1577 of 1969 [80.1%]; P < .001). Transitioning patients from IV to oral therapy by day 7 was highly variable across hospitals, ranging from 25.8% (66 of 256) to 65.9% (27 of 41). A total of 4109 patients (89.7%) achieved clinical stability within 5 days. For the 3429 episodes (74.9%) with successful source control by day 7, the median day of source control was day 2 (IQR, 1-3 days) for the oral group and day 2 (IQR, 1-4 days) for the IV group (P < .001). Common infection sources among patients administered oral therapy were the urinary tract (1277 of 1969 [64.9%]), hepatobiliary (239 of 1969 [12.1%]), and intra-abdominal (194 of 1969 [9.9%]). The median day of oral transition was 5 (IQR, 4-6 days). Total duration of antibiotic treatment was significantly shorter among the oral group than the IV group (median, 11 days [IQR, 9-14 days] vs median, 13 days [IQR, 8-16 days]; P < .001]. Fluoroquinolones (62.2% [1224 of 1969]), followed by ß-lactams (28.3% [558 of 1969]) and trimethoprim-sulfamethoxazole (11.5% [227 of 1969]), were the most commonly prescribed oral antibiotics. Conclusions and Relevance: In this cohort study of 4581 episodes of GN-BSIs, transition to oral antibiotic therapy by day 7 occurred in fewer than half of episodes, principally with fluoroquinolones, although this practice varied significantly between hospitals. There may have been additional opportunities for earlier and more frequent oral antibiotic transitions because most patients demonstrated clinical stability by day 5.

Interventions to de-implement unnecessary antibiotic prescribing for ear infections (DISAPEAR Trial): protocol for a cluster-randomized trial.

BACKGROUND: Watchful waiting management for acute otitis media (AOM), where an antibiotic is used only if the child's symptoms worsen or do not improve over the subsequent 2-3 days, is an effective approach to reduce antibiotic exposure for children with AOM. However, studies to compare the effectiveness of interventions to promote watchful waiting are lacking. The objective of this study is to compare the effectiveness and implementation outcomes of two pragmatic, patient-centered interventions designed to facilitate use of watchful waiting in clinical practice. METHODS: This will be a cluster-randomized trial utilizing a hybrid implementation-effectiveness design. Thirty-three primary care or urgent care clinics will be randomized to one of two interventions: a health systems-level intervention alone or a health systems-level intervention combined with use of a shared decision-making aid. The health systems-level intervention will include engagement of a clinician champion at each clinic, changes to electronic health record antibiotic orders to facilitate delayed antibiotic prescriptions as part of a watchful waiting strategy, quarterly feedback reports detailing clinicians' use of watchful waiting individually and compared with peers, and virtual learning sessions for clinicians. The hybrid intervention will include the health systems-level intervention plus a shared decision-making aid designed to inform decision-making between parents and clinicians with best available evidence. The primary outcomes will be whether an antibiotic was ultimately taken by the child and parent satisfaction with their child's care. We will explore the differences in implementation effectiveness by patient population served, clinic type, clinical setting, and organization. The fidelity, acceptability, and perceived appropriateness of the interventions among different clinician types, patient populations, and clinical settings will be compared. We will also conduct formative qualitative interviews and surveys with clinicians and administrators, focus groups and surveys of parents of patients with AOM, and engagement of two stakeholder advisory councils to further inform the interventions. DISCUSSION: This study will compare the effectiveness of two pragmatic interventions to promote use of watchful waiting for children with AOM to reduce antibiotic exposure and increase parent satisfaction, thus informing national antibiotic stewardship policy development. CLINICAL TRIAL REGISTRATION: NCT06034080.

Impact of an antibiotic stewardship initiative on urgent-care respiratory prescribing across patient race, ethnicity, and language.

We conducted a post hoc analysis of an antibiotic stewardship intervention implemented across our health system's urgent-care network to determine whether there was a differential impact among patient groups. Respiratory urgent-care antibiotic prescribing decreased for all racial, ethnic, and preferred language groups, but disparities in antibiotic prescribing persisted.

The current state of antimicrobial and urine culture stewardship in Thailand: Results from a national survey.

BACKGROUND: Antimicrobial stewardship in Thailand has made major progress backed by a national strategic plan. The current study aimed to assess the antimicrobial stewardship program (ASP) composition, reach, and breadth, as well as urine culture stewardship in Thai hospitals. METHODS: We sent an electronic survey to 100 Thai hospitals between February 1, 2021 and August 31, 2021. This hospital sample represented 20 hospitals in each of Thailand's 5 geographical regions. RESULTS: The response rate was 100%. A total of 86 of 100 hospitals had an ASP. These were often multi-disciplinary in nature, with half including infectious disease-trained physicians and pharmacists, infection preventionists, and nursing staff. Urine culture stewardship protocols existed in 51% of hospitals. CONCLUSIONS: The national strategic plan in Thailand has allowed the country to stand up robust ASPs. Further research should examine the effectiveness of such programs and ways to expand them into other medical settings, like nursing homes, urgent care, and outpatient while continuing to grow telehealth and urine culture stewardship.

Pyoderma gangrenosum and impact on quality of life: A narrative review.

Pyoderma gangrenosum (PG) is an autoinflammatory disorder typically characterized by progressive ulcers with dense neutrophilic infiltrates in the absence of infectious causes. The chronic nature of this disease significantly impacts the patients' quality of life (QoL). Yet there is currently a dearth of information in the literature regarding standardised treatment guidelines and the impact of PG on patients' QoL. We conducted a literature search on PubMed using the terms "pyoderma gangrenosum" AND "quality of life." We identified nine relevant articles that provide insight into which domains are affected and what treatment can improve QoL. The most common domains involved are physical, emotional, and psychological. Patients tend to feel depressed/anxious, isolated, and embarrassed secondary to PG manifestations. Comorbidities such as Crohn's disease, monoclonal gammopathy of dermatologic significance, and ulcerative colitis can worsen the impact on these patients' QoL. Pain is also a significant contributor to decreasing patients' QoL. Treatments such as topical steroids, adalimumab, and canakinumab may help improve QoL scores. We believe this information can help clinicians guide the care of patients with PG and highlight the need for more studies and clinical trials focusing on PG treatments' impact on QoL.

Defining access without excess: expanding appropriate use of antibiotics targeting multidrug-resistant organisms.

Antimicrobial resistance remains a significant global public health threat. Although development of novel antibiotics can be challenging, several new antibiotics with improved activity against multidrug-resistant Gram-negative organisms have recently been commercialised. Expanding access to these antibiotics is a global public health priority that should be coupled with improving access to quality diagnostics, health care with adequately trained professionals, and functional antimicrobial stewardship programmes. This comprehensive approach is essential to ensure responsible use of these new antibiotics.

Excellence in Antibiotic Stewardship: A mixed methods study comparing High, Medium, and Low Performing Hospitals.

BACKGROUND: Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood. METHODS: We conducted an explanatory, sequential mixed methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse. For each hospital, we conducted surveys, document analysis, and semi-structured interviews with antibiotic stewardship and clinical stakeholders. Data were analyzed separately and mixed during the interpretation phase, where each hospital was examined as a case, with findings organized across cases using a strengths, weaknesses, opportunities, and threats framework to identify factors accounting for differences in antibiotic overuse across hospitals. RESULTS: Surveys included 85 respondents. Interviews included 90 respondents (31 hospitalists, 33 clinical pharmacists, 14 stewardship leaders, 12 hospital leaders). On surveys, clinical pharmacists at hospitals with lower antibiotic overuse were more likely to report feeling: respected by hospitalist colleagues (p=0.001), considered valuable team members (p=0.001), comfortable recommending antibiotic changes (p=0.02). Based on mixed-methods analysis, hospitals with low antibiotic overuse had four distinguishing characteristics: a) robust knowledge of and access to antibiotic stewardship guidance, b) high quality clinical pharmacist-physician relationships, c) tools and infrastructure to support stewardship, and d) highly engaged Infectious Diseases physicians who advocated stewardship principles. CONCLUSION: This mixed-method study demonstrates the importance of organizational context for high performance in stewardship and suggests improving antimicrobial stewardship requires attention to knowledge, interactions, and relationships between clinical teams and infrastructure that supports stewardship and team interactions.

The Infectious Diseases Society of America Guidelines on the Diagnosis of Coronavirus Disease 2019 (COVID-19): Molecular Diagnostic Testing.

Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19) and for identifying asymptomatic carriage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of available SARS-CoV-2 nucleic acid detection tests continues to increase as does the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) developed an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss nuances of test result interpretation in a variety of practice settings, and highlight important unmet research needs related to COVID-19 diagnostic testing. IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 12 diagnostic recommendations. Access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public health response to COVID-19 infection. Information on the clinical performance of available tests continues to grow, but the quality of evidence of the current literature to support this updated molecular diagnostic guideline remains moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is suggested for asymptomatic individuals with known or suspected contact with a COVID-19 case when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions. Evidence in support of rapid testing and testing of upper respiratory specimens other than nasopharyngeal swabs, which offer logistical advantages, is sufficient to warrant conditional recommendations in favor of these approaches.

Understanding refugee and immigrant health literacy and beliefs toward antimicrobial resistance.

Refugee and migrant populations have increased vulnerability to antimicrobial resistance, yet stewardship guidance is lacking. We addressed this gap through a cross-sectional survey, finding that these populations and immigrants from low and middle-income countries had lower health literacy on the issue compared to native-born Americans and those from high-income countries.

Drivers of inappropriate use of antimicrobials in South Asia: A systematic review of qualitative literature.

Antimicrobial resistance is a global public health crisis. Effective antimicrobial stewardship requires an understanding of the factors and context that contribute to inappropriate use of antimicrobials. The goal of this qualitative systematic review was to synthesize themes across levels of the social ecological framework that drive inappropriate use of antimicrobials in South Asia. In September 2023, we conducted a systematic search using the electronic databases PubMed and Embase. Search terms, identified a priori, were related to research methods, topic, and geographic location. We identified 165 articles from the initial search and 8 upon reference review (n=173); after removing duplicates and preprints (n=12) and excluding those that did not meet eligibility criteria (n=115), 46 articles were included in the review. We assessed methodological quality using the qualitative Critical Appraisal Skills Program checklist. The studies represented 6 countries in South Asia, and included data from patients, health care providers, community members, and policy makers. For each manuscript, we wrote a summary memo to extract the factors that impede antimicrobial stewardship. We coded memos using NVivo software; codes were organized by levels of the social ecological framework. Barriers were identified at multiple levels including the patient (self-treatment with antimicrobials; perceived value of antimicrobials), the provider (antimicrobials as a universal therapy; gaps in knowledge and skills; financial or reputational incentives), the clinical setting (lack of resources; poor regulation of the facility), the community (access to formal health care; informal drug vendors; social norms), and policy (absence of a regulatory framework; poor implementation of existing policies). The findings highlight the importance of working across multiple sectors to design and implement approaches to antimicrobial stewardship in South Asia.

Introduction to A Compendium of Strategies to Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates.

Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients, leading to substantial morbidity, mortality, and excess healthcare expenditures, and persistent gaps remain between what is recommended and what is practiced.The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.

C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita.

Introduction: Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype. Methods: To better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome. Results: Through this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e-/- and Clec4d-/- mice as well as in neutrophil-specific Clec4n-/- mice. Deficiency in these genes did not reduce disease in the EBA model. Discussion: Collectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.