The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

IMPORTANCE: Many recent advances in pediatric concussion care are implemented by specialists; however, children with concussion receive care across varied locations. Thus, it is critical to identify which children have access to the most up-to-date treatment strategies. OBJECTIVE: To evaluate differences in the sociodemographic and community characteristics of pediatric patients who sought care for concussion across various points of entry into a regional health care network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included children seen for concussions across a regional US health care network from January 1, 2017, to August 4, 2023. Pediatric patients aged 0 to 18 years who received an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification code for concussion were included. The study took place at emergency department (ED) and outpatient (primary care [PC] and specialty care [SC]) settings. EXPOSURES: Age at visit, biological sex, parent-identified race and ethnicity, payer type, median income and percentage of adults with a bachelor's degree for home zip code, and overall and subdomain Child Opportunity Index (COI) score based on patient address. MAIN OUTCOMES AND MEASURES: The association of exposures with point of entry of ED, PC, and SC were examined in both bivariate analysis and a multinomial logistic regression. RESULTS: Overall, 15 631 patients were included in the study (median [IQR] age, 13 [11-15] years; 7879 [50.4%] male; 1055 [6.7%] Hispanic, 2865 [18.3%] non-Hispanic Black, and 9887 [63.7%] non-Hispanic White individuals). Race and ethnicity were significantly different across settings (1485 patients [50.0%] seen in the ED were non-Hispanic Black vs 1012 [12.0%] in PC and 368 [8.7%] in SC; P < .001) as was insurance status (1562 patients [52.6%] seen in the ED possessed public insurance vs 1624 [19.3%] in PC and 683 [16.1%] in SC; P < .001). Overall and individual COI subdomain scores were also significantly different between settings (overall COI median [IQR]: ED, 30 [9-71]; PC, 87 [68-95]; SC, 87 [69-95]; P < .001). Race, insurance status, and overall COI had the strongest associations with point of entry in the multivariable model (eg, non-Hispanic Black patients seen in the ED compared with non-Hispanic White patients: odds ratio, 2.03; 95% CI, 1.69-2.45). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, children with concussion seen in the ED setting were more likely to be non-Hispanic Black, have public insurance, and have a lower Child Opportunity Index compared with children cared for in the PC or SC setting. This highlights the importance of providing education and training for ED clinicians as well as establishing up-to-date community-level resources to optimize care delivery for pediatric patients with concussion at high risk of care inequities.

RATIONALE: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/ACTG A5349 represents the largest Phase 3 randomized controlled therapeutic trial to date for such investigation. OBJECTIVES: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure with efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. METHODS: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. MEASUREMENTS AND MAIN RESULTS: Among 2255 participants with 6978 plasma samples, pyrazinamide displayed 7-fold exposure variability (151-1053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in a therapeutic window of 231-355 mg·h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1000 mg would have permitted an additional 13.1% (n=96) participants allocated to the control and 9.2% (n=70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared to the current weight-banded dosing. CONCLUSIONS: Flat dosing of pyrazinamide at 1000 mg daily would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772.

INTRODUCTION: Over 30 million U.S. working adults use tobacco, and tobacco use varies by occupation. Limited information is available on employment characteristics and tobacco use prevalence. The purpose of this study was to describe the prevalence of current tobacco use by employment characteristics and occupation group among U.S. working adults. METHODS: This cross-sectional study used 2021 National Health Interview Survey data for currently working adults (n=16,461) analyzed in 2023. Multivariable logistic regression was used to estimate adjusted odds of tobacco use by employment characteristics and occupation group. RESULTS: In 2021, 20.0% of working adults used tobacco. Any tobacco use was significantly lower among workers who were offered workplace health insurance (aOR=0.86, 95% CI=0.77-0.97), had paid sick leave (aOR=0.81, 95% CI=0.73-0.91), and government vs. private employment (aOR=0.61, 95% CI=0.52-0.70). Any tobacco use was significantly higher among workers who usually worked ≥35 hours per week vs. did not usually work ≥35 hours per week (aOR=1.21, 95% CI=1.06-1.39), worked a rotating or 'some other' shift vs. daytime shift (aOR=1.19, 95% CI=1.02-1.38), experienced schedule instability (aOR=1.17, 95% CI=1.03-1.31), and worked while physically ill in the past 3 months (aOR=1.25, 95% CI=1.11-1.41). Tobacco use by employment characteristics also varied by occupation group. CONCLUSIONS: Current tobacco use varied according to employment characteristics and occupation group. Findings from this study could inform workplace tobacco cessation interventions and policies (e.g., access to paid sick leave or insurance coverage) to better support tobacco cessation and overall worker health.

Candida auris is an emerging fungal pathogen that typically affects patients in healthcare settings. Data on C. auris cases in correctional facilities are limited but are needed to guide public health recommendations. We describe cases and challenges of providing care for 13 patients who were transferred to correctional facilities during January 2020-December 2022 after having a positive C. auris specimen. All patients had positive specimens identified while receiving inpatient care at healthcare facilities in geographic areas with high C. auris prevalence. Correctional facilities reported challenges managing patients and implementing prevention measures; those challenges varied by whether patients were housed in prison medical units or general population units. Although rarely reported, C. auris cases in persons who are incarcerated may occur, particularly in persons with known risk factors. Measures to manage cases and prevent C. auris spread in correctional facilities should address setting-specific challenges in healthcare and nonhealthcare correctional environments.

On July 2, 2021, MMWR published “Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic — United States, March–April 2021” (1). On October 12, 2021, the authors informed MMWR that some data were inaccurate because 420 incomplete participant responses were incorrectly assigned scores for depression. This error resulted in a change in overall depression prevalence from 32.0% to 30.8%, and other similar changes in stratified prevalences of depression, prevalence ratios of depression, and the overall proportion of respondents who reported at least one mental health condition. The authors have corrected the MMWR report by excluding the 420 records from the depression analysis and confirmed that the interpretation and the conclusions of the original report were not affected by these corrections. MMWR has republished the report (2), which includes the original report with clearly marked corrections in supplementary materials.

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the Phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months, TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models, and all trial-defined safety outcomes using logistic regression. RESULTS: Our model derived rifampicin exposure ranged from 4.57 mg·h/L to 140.0 mg·h/L with a median of 41.8 mg·h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to weight-banded dose. Exposure-efficacy analysis (N=680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared to those with exposure above the median. Exposure-safety analysis (N=722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events, or serious adverse events. CONCLUSIONS: Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard of care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation.

The nationwide scale-up of evidence-based and evidence-informed interventions has been widely recognized as a crucial step in ending the HIV epidemic. Although the successful delivery of interventions may involve intensive expert training, technical assistance (TA), and dedicated funding, most organizations attempt to replicate interventions without access to focused expert guidance. Thus, there is a grave need for initiatives that meaningfully address HIV health disparities while addressing these inherent limitations. Here, the Health Resources and Services Administration HIV/AIDS Bureau (HRSA HAB) initiative Using Evidence-Informed Interventions to Improve HIV Health Outcomes among People Living with HIV (E2i) piloted an alternative approach to implementation that de-emphasized expert training to naturalistically simulate the experience of future HIV service organizations with limited access to TA. The E2i approach combined the HAB-adapted Institute for Healthcare Improvement's Breakthrough Series Collaborative Learning Model with HRSA HAB's Implementation Science Framework, to create an innovative multi-tiered system of peer-to-peer learning that was piloted across 11 evidence-informed interventions at 25 Ryan White HIV/AIDS Program sites. Four key types of peer-to-peer learning exchanges (i.e., intervention, site, staff role, and organization specific) took place at biannual peer learning sessions, while quarterly intervention cohort calls and E2i monthly calls with site staff occurred during the action periods between learning sessions. Peer-to-peer learning fostered both experiential learning and community building and allowed site staff to formulate robust site-specific action plans for rapid cycle testing between learning sessions. Strategies that increase the effectiveness of interventions while decreasing TA could provide a blueprint for the rapid uptake and integration of HIV interventions nationwide.

Background: La Crosse virus is an important endemic public health concern in the North Carolina Appalachian Mountains; however, human incidence is not commonly noted in this region on the South Carolina side of the mountain range border. No relevant studies have been performed in South Carolina evaluating mosquito vector populations for La Crosse virus (LACV) infection; thus, a pilot mosquito surveillance study was executed in summer 2020. Material and Methods: Vector surveillance occurred at five South Carolina state parks bordering neighboring state endemic counties from May to August 2020. Collections were approved by the state park authority, as noted in Permit No. N-8-20. Results: All three competent mosquito vectors were collected during the study duration; however, these vectors were collected in low abundance: Aedes triseriatus (4.5% of all collected mosquitos); Aedes albopictus (2.0%); Aedes japonicus (1.4%). Principal mosquito vector specimens, Ae. triseriatus, were sent to Centers for Disease Control and Prevention for testing of LACV by real-time reverse transcription PCR-all were negative. Discussion: While entomologic evidence suggests low transmission risk for this arbovirus in the South Carolina Appalachian Mountain region, further eco-epidemiologic investigations are warranted to understand this endemicity variance within a relatively small geographic area.

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.

Strategies to prevent catheter-associated urinary tract infections (CAUTIs) | Essential practices | Infrastructure and resources | 1 Perform a CAUTI risk assessment and implement an organization-wide program to identify and remove catheters that are no longer necessary using 1 or | more methods documented to be effective. (Quality of evidence: MODERATE) | 2 Provide appropriate infrastructure for preventing CAUTI. (Quality of evidence: LOW) | 3 Provide and implement evidence-based protocols to address multiple steps of the urinary catheter life cycle: catheter appropriateness (step 0), insertion | technique (step 1), maintenance care (step 2), and prompt removal (step 3) when no longer appropriate. (Quality of evidence: LOW) | 4 Ensure that only trained healthcare personnel (HCP) insert urinary catheters and that competency is assessed regularly. (Quality of evidence: LOW) | 5 Ensure that supplies necessary for aseptic technique for catheter insertion are available and conveniently located. (Quality of evidence: LOW) | 6 Implement a system for documenting the following in the patient record: physician order for catheter placement, indications for catheter insertion, date | and time of catheter insertion, name of individual who inserted catheter, nursing documentation of placement, daily presence of a catheter and | maintenance care tasks, and date and time of catheter removal. Record criteria for removal and justification for continued use. (Quality of evidence: | LOW) | 7 Ensure that sufficiently trained HCP and technology resources are available to support surveillance for catheter use and outcomes. (Quality of evidence: | LOW) | 8 Perform surveillance for CAUTI if indicated based on facility risk assessment or regulatory requirements. (Quality of evidence: LOW) | 9 Standardize urine culturing by adapting an institutional protocol for appropriate indications for urine cultures in patients with and without indwelling | catheters. Consider incorporating these indications into the electronic medical record, and review indications for ordering urine cultures in the CAUTI | risk assessment. (Quality of evidence: LOW) | Education and training | 1 Educate HCP involved in the insertion, care, and maintenance of urinary catheters about CAUTI prevention, including alternatives to indwelling | catheters, and procedures for catheter insertion, management, and removal. (Quality of evidence: LOW) | 2 Assess healthcare professional competency in catheter use, catheter care, and maintenance. (Quality of evidence: LOW) | 3 Educate HCP about the importance of urine-culture stewardship and provide indications for urine cultures. (Quality of evidence: LOW) | 4 Provide training on appropriate collection of urine. Specimens should be collected and should arrive at the microbiology laboratory as soon as possible, | preferably within an hour. If delay in transport to the laboratory is expected, samples should be refrigerated (no more than 24 hours) or collected in | preservative urine transport tubes. (Quality of evidence: LOW) | 5 Train clinicians to consider other methods for bladder management, such as intermittent catheterization or external male or female collection devices, | when appropriate, before placing an indwelling urethral catheter. (Quality of evidence: LOW) | 6 Share data in a timely fashion and report to appropriate stakeholders. (Quality of evidence: LOW) | Insertion of indwelling catheters | 1 Insert urinary catheters only when necessary for patient care and leave in place only as long as indications remain. (Quality of evidence: MODERATE) | 2 Consider other methods for bladder management such as intermittent catheterization, or external male or female collection devices, when appropriate. | (Quality of evidence: LOW) | 3 Use appropriate technique for catheter insertion. (Quality of evidence: MODERATE). | 4 Consider working in pairs to help perform patient positioning and monitor for potential contamination during placement. (Quality of evidence: LOW) | 5 Practice hand hygiene (based on CDC or WHO guidelines) immediately before insertion of the catheter and before and after any manipulation of the | catheter site or apparatus. (Quality of evidence: LOW) | 6 Insert catheters following aseptic technique and using sterile equipment. (Quality of evidence: LOW) | 7 Use sterile gloves, drape, and sponges, a sterile antiseptic solution for cleaning the urethral meatus, and a sterile single-use packet of lubricant jelly for | insertion. (Quality of evidence: LOW) | 8 Use a catheter with the smallest feasible diameter consistent with proper drainage to minimize urethral trauma but consider other catheter types and | sizes when warranted for patients with anticipated difficult catheterization to reduce the likelihood that a patient will experience multiple, sometimes | traumatic, catheterization attempts. (Quality of evidence: LOW) | Management of indwelling catheters | 1 Properly secure indwelling catheters after insertion to prevent movement and urethral traction. (Quality of evidence: LOW) | 2 Maintain a sterile, continuously closed drainage system. (Quality of evidence: LOW) | 3 Replace the catheter and the collecting system using aseptic technique when breaks in aseptic technique, disconnection, or leakage occur. (Quality of | evidence: LOW) | 4 For examination of fresh urine, collect a small sample by aspirating urine from the needleless sampling port with a sterile syringe/cannula adaptor after | cleansing the port with disinfectant. (Quality of evidence: LOW) | (Continued) | 2 Deborah S. Yokoe et al | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Strategies to prevent central-line–associated bloodstream infections (CLABSIs) | (Continued ) | 5 Facilitate timely transport of urine samples to laboratory. If timely transport is not feasible, consider refrigerating urine samples or using samplecollection cups with preservatives. Obtain larger volumes of urine for special analyses (eg, 24-hour urine) aseptically from the drainage bag. (Quality of | evidence: LOW) | 6 Maintain unobstructed urine flow. (Quality of evidence: LOW) | 7 Employ routine hygiene. Cleaning the meatal area with antiseptic solutions is an unresolved issue, though emerging literature supports chlorhexidine | use prior to catheter insertion. Alcohol-based products should be avoided given concerns about the alcohol causing drying of the mucosal tissues. | (Quality of evidence: LOW) | Additional approaches | 1 Develop a protocol for standardizing diagnosis and management of postoperative urinary retention, including nurse-directed use of intermittent | catheterization and use of bladder scanners when appropriate as alternatives to indwelling urethral catheterization. (Quality of evidence: MODERATE) | 2 Establish a system for analyzing and reporting data on catheter use and adverse events from catheter use. (Quality of evidence: LOW) | 3 Establish a system for defining, analyzing, and reporting data on non–catheter-associated UTIs, particularly UTIs associated with the use of devices | being used as alternatives to indwelling urethral catheters. (Quality of evidence: LOW) | Essential practices | Before insertion | 1 Provide easy access to an evidence-based list of indications for CVC use to minimize unnecessary CVC placement. (Quality of evidence: LOW) | 2 Require education and competency assessment of healthcare personnel (HCP) involved in insertion, care and maintenance of CVCs about CLABSI | prevention. (Quality of evidence: MODERATE) | 3 Bathe ICU patients aged >2 months with a chlorhexidine preparation on a daily basis. (Quality of evidence: HIGH) | At insertion | 1 In ICU and non-ICU settings, a facility should have a process in place, such as a checklist, to ensure adherence to infection prevention practices at the | time of CVC insertion. (Quality of evidence: MODERATE) | 2 Perform hand hygiene prior to catheter insertion or manipulation. (Quality of evidence: MODERATE) | 3 The subclavian site is preferred to reduce infectious complications when the catheter is placed in the ICU setting. (Quality of evidence: HIGH) | 4 Use an all-inclusive catheter cart or kit. (Quality of evidence: MODERATE) | 5 Use ultrasound guidance for catheter insertion. (Quality of evidence: HIGH) | 6 Use maximum sterile barrier precautions during CVC insertion. (Quality of evidence: MODERATE) | After insertion | 1 Ensure appropriate nurse-to-patient ratio and limit use of float nurses in ICUs. (Quality of evidence: HIGH) | 2 Use chlorhexidine-containing dressings for CVCs in patients aged >2 months. (Quality of evidence: HIGH) | 3 For nontunneled CVCs in adults and children, change transparent dressings and perform site care with a chlorhexidine-based antiseptic at least every 7 | days or immediately if the dressing is soiled, loose, or damp. Change gauze dressings every 2 days or earlier if the dressing is soiled, loose, or damp. | (Quality of evidence: MODERATE) | 4 Disinfect catheter hubs, needleless connectors, and injection ports before accessing the catheter. (Quality of evidence: MODERATE) | 5 Remove nonessential catheters. (Quality of evidence: MODERATE) | 6 Routine replacement of administration sets not used for blood, blood products, or lipid formulations can be performed at intervals up to 7 days. | (Quality of evidence: HIGH) | 7 Perform surveillance for CLABSI in ICU and non-ICU settings. (Quality of evidence: HIGH) | Additional approaches | 1 Use antiseptic or antimicrobial-impregnated CVCs. (Quality of evidence: HIGH in adult patients; MODERATE in pediatric patients) | 2 Use antimicrobial lock therapy for long-term CVCs. (Quality of evidence: HIGH) | 3 Use recombinant tissue plasminogen activating factor (rt-PA) once weekly after hemodialysis in patients undergoing hemodialysis through a CVC. | (Quality of evidence: HIGH) | 4 Utilize infusion or vascular access teams for reducing CLABSI rates. (Quality of evidence: LOW) | 5 Use antimicrobial ointments for hemodialysis catheter-insertion sites. (Quality of evidence: HIGH) | 6 Use an antiseptic-containing hub, connector cap, or port protector to cover connectors. (Quality of evidence: MODERATE) | Infection Control & Hospital Epidemiology 3 | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Strategies to prevent Clostridioides difficile infections (CDIs) | Strategies to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission and infection | Essential practices | 1 Encourage appropriate use of antimicrobials through implementation of an antimicrobial stewardship program. (Quality of evidence: MODERATE) | 2 Implement diagnostic stewardship practices for ensuring appropriate use and interpretation of C. difficile testing. (Quality of evidence: LOW) | 3 Use contact precautions for infected patients, single-patient room preferred. (Quality of evidence: LOW for hand hygiene; MODERATE for gloves; LOW | for gowns; LOW for single-patient room) | 4 Adequately clean and disinfect equipment and the environment of patients with CDI. (Quality of evidence: LOW for equipment; LOW for environment) | 5 Assess the adequacy of room cleaning. (Quality of evidence: LOW) | 6 Implement a laboratory-based alert system to provide immediate notification to infection preventionists and clinical personnel about newly diagnosed | patients with CDI. (Quality of evidence: LOW) | 7 Conduct CDI surveillance and analyze and report CDI data. (Quality of evidence: LOW) | 8 Educate healthcare personnel (HCP), environmental service personnel, and hospital administration about CDI. (Quality of evidence: LOW) | 9 Educate patients and their families about CDI as appropriate. (Quality of evidence: LOW) | 10 Measure compliance with CDC or WHO hand hygiene and contact precaution recommendations. (Quality of evidence: LOW) | Additional approaches | 1 Intensify the assessment of compliance with process measures. (Quality of evidence: LOW) | 2 Perform hand hygiene with soap and water as the preferred method following care of or interacting with the healthcare environment of a patient with | CDI. (Quality of evidence: LOW) | 3 Place patients with diarrhea on contact precautions while C. difficile testing is pending. (Quality of evidence: LOW) | 4 Prolong the duration of contact precautions after the patient becomes asymptomatic until hospital discharge. (Quality of evidence: LOW) | 5 Use an EPA-approved sporicidal disinfectant, such as diluted (1:10) sodium hypochlorite, for environmental cleaning and disinfection. Implement a | system to coordinate with environmental services if it is determined that sodium hypochlorite is needed for environmental disinfection. (Quality of | evidence: LOW) | Essential practices | 1 Implement an MRSA monitoring program. (Quality of evidence: LOW) | 2 Conduct an MRSA risk assessment. (Quality of evidence: LOW) | 3 Promote compliance with CDC or World Health Organization (WHO) hand hygiene recommendations. (Quality of evidence: MODERATE) | 4 Use contact precautions for MRSA-colonized and MRSA-infected patients. A facility that chooses or has already chosen to modify the use of contact | precautions for some or all of these patients should conduct an MRSA-specific risk assessment to evaluate the facility for transmission risks and to | assess the effectiveness of other MRSA risk mitigation strategies (eg, hand hygiene, cleaning and disinfection of the environment, single occupancy | patient rooms) and should establish a process for ongoing monitoring, oversight, and risk assessment. (Quality of evidence: MODERATE) | 5 Ensure cleaning and disinfection of equipment and the environment. (Quality of evidence: MODERATE) | 6 Implement a laboratory-based alert system that notifies healthcare personnel (HCP) of new MRSA-colonized or MRSA-infected patients in a timely | manner. (Quality of evidence: LOW) | 7 Implement an alert system that identifies readmitted or transferred MRSA-colonized or MRSA-infected patients. (Quality of evidence: LOW) | 8 Provide MRSA data and outcome measures to key stakeholders, including senior leadership, physicians, nursing staff, and others. (Quality of evidence: | LOW) | 9 Educate healthcare personnel about MRSA. (Quality of evidence: LOW) | 10 Educate patients and families about MRSA. (Quality of evidence: LOW) | 11 Implement an antimicrobial stewardship program. (Quality of evidence: LOW) | Additional approaches | Active surveillance testing (AST) | 1 Implement an MRSA AST program for select patient populations as part of a multifaceted strategy to control and prevent MRSA. (Quality of evidence: | MODERATE) Note: specific populations may have different evidence ratings. | 2 Active surveillance for MRSA in conjunction with decolonization can be performed in targeted populations prior to surgery to prevent postsurgical | MRSA infection. (Quality of evidence: MODERATE) | (Continued) | 4 Deborah S. Yokoe et al | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Strategies to prevent surgical-site infections (SSIs) | (Continued ) | 3 Active surveillance with contact precautions is inferior to universal decolonization for reduction of MRSA clinical isolates in adult ICUs. (Quality of | evidence: HIGH) | 4 Hospital-wide active surveillance for MRSA can be used in conjunction with contact precautions to reduce the incidence of MRSA infection. (Quality of | evidence: MODERATE) | 5 Active surveillance can be performed in the setting of an MRSA outbreak or evidence of ongoing transmission of MRSA within a unit as part of a | multifaceted strategy to halt transmission. (Quality of evidence: MODERATE) | Screen healthcare personnel for MRSA infection or colonization | 1 Screen HCP for MRSA infection or colonization if they are epidemiologically linked to a cluster of MRSA infections. (Quality of evidence: LOW) | MRSA decolonization therapy | 1 Use universal decolonization (ie, daily CHG bathing plus 5 days of nasal decolonization) for all patients in adult ICUs to reduce endemic MRSA clinical | cultures. (Quality of evidence: HIGH) | 2 Perform preoperative nares screening with targeted use of CHG and nasal decolonization in MRSA carriers to reduce MRSA SSI from surgical | procedures involving implantation of hardware. (Quality of evidence: MODERATE) | 3 Screen for MRSA and provide targeted decolonization with CHG bathing and nasal decolonization to MRSA carriers in surgical units to reduce | postoperative MRSA inpatient infections. (Quality of evidence: MODERATE) | 4 Provide CHG bathing plus nasal decolonization to known MRSA carriers outside the ICU with medical devices, specifically central lines, midline | catheters, and lumbar drains to reduce MRSA clinical cultures. (Quality of evidence: MODERATE) | 5 Consider postdischarge decolonization of MRSA carriers to reduce postdischarge MRSA infections and readmissions. (Quality of evidence: HIGH) | 6 Neonatal ICUs should consider targeted or universal decolonization during times of above-average MRSA infection rates or targeted decolonization for | patients at high risk of MRSA infection (eg, low birth weight, indwelling devices, or prior to high-risk surgeries). (Quality of evidence: MODERATE) | 7 Burn units should consider targeted or universal decolonization during times of above-average MRSA infection rates. (Quality of evidence: MODERATE) | 8 Consider targeted or universal decolonization of hemodialysis patients. (Quality of evidence: MODERATE) | 9 Decolonization should be strongly considered as part of a multimodal approach to control MRSA outbreaks. (Quality of evidence: MODERATE) | Universal use of gowns and gloves | 1 Use gowns and gloves when providing care to or entering the room of any adult ICU patient, regardless of MRSA colonization status. (Quality of | evidence: MODERATE) | Essential practices | 1 Administer antimicrobial prophylaxis according to evidence-based standards and guidelines. (Quality of evidence: HIGH) | 2 Use a combination of parenteral and oral antimicrobial prophylaxis prior to elective colorectal surgery to reduce the risk of SSI. (Quality of evidence: | HIGH) | 3 Decolonize surgical patients with an anti-staphylococcal agent in the preoperative setting for orthopedic and cardiothoracic procedures. (Quality of | evidence: HIGH) | Decolonize surgical patients in other procedures at high risk of staphylococcal SSI, such as those involving prosthetic material. (Quality of evidence: | LOW) | 4 Use antiseptic-containing preoperative vaginal preparation agents for patients undergoing cesarean delivery or hysterectomy. (Quality of evidence: | MODERATE) | 5 Do not remove hair at the operative site unless the presence of hair will interfere with the surgical procedure. (Quality of evidence: MODERATE) | 6 Use alcohol-containing preoperative skin preparatory agents in combination with an antiseptic. (Quality of evidence: HIGH) | 7 For procedures not requiring hypothermia, maintain normothermia (temperature >35.5 °C) during the perioperative period. (Quality of evidence: HIGH). | 8 Use impervious plastic wound protectors for gastrointestinal and biliary tract surgery. (Quality of evidence: HIGH) | 9 Perform intraoperative antiseptic wound lavage. (Quality of evidence: MODERATE) | 10 Control blood glucose level during the immediate postoperative period for all patients. (Quality of evidence: HIGH) | 11 Use a checklist and/or bundle to ensure compliance with best practices to improve surgical patient safety. (Quality of evidence: HIGH) | 12 Perform surveillance for SSI. (Quality of evidence: MODERATE) | 13 Increase the efficiency of surveillance by utilizing automated data. (Quality of evidence: MODERATE) | 14 Provide ongoing SSI rate feedback to surgical and perioperative personnel and leadership. (Quality of evidence: MODERATE) | 15 Measure and provide feedback to healthcare personnel (HCP) regarding rates of compliance with process measures. (Quality of evidence: LOW) | (Continued) | Infection Control & Hospital Epidemiology 5 | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Strategies to prevent ventilator-associated pneumonia (VAP) and ventilator-associated events (VAEs) | Adult patients | (Continued ) | 16 Educate surgeons and perioperative personnel about SSI prevention measures. (Quality of evidence: LOW) | 17 Educate patients and their families about SSI prevention as appropriate. (Quality of evidence: LOW) | 18 Implement policies and practices to reduce the risk of SSI for patients that align with applicable evidence-based standards, rules and regulations, and | medical device manufacturer instructions for use. (Quality of evidence: MODERATE) | 19 Observe and review operating room personnel and the environment of care in the operating room and in central sterile reprocessing. (Quality of | evidence: LOW) | Additional approaches | 1 Perform an SSI risk assessment. (Quality of evidence: LOW) | 2 Consider use of negative-pressure dressings in patients who may benefit. (Quality of evidence: MODERATE) | 3 Observe and review practices in the preoperative clinic, post-anesthesia care unit, surgical intensive care unit, and/or surgical ward. (Quality of | evidence: MODERATE) | 4 Use antiseptic-impregnated sutures as a strategy to prevent SSI. (Quality of evidence: MODERATE) | Essential practices | Interventions with little risk of harm and that are associated with decreases in duration of mechanical ventilation, length of stay, mortality, antibiotic utilization, | and/or costs | Avoid intubation and prevent reintubation if possible. | 1 Use high flow nasal oxygen or non-invasive positive pressure ventilation (NIPPV) as appropriate, whenever safe and feasible. (Quality of evidence: HIGH) | Minimize sedation. | 1 Minimize sedation of ventilated patients whenever possible. (Quality of evidence: HIGH) | 2 Preferentially use multimodal strategies and medications other than benzodiazepines to manage agitation. (Quality of evidence: HIGH) | 3 Utilize a protocol to minimize sedation. (Quality of evidence: HIGH) | 4 Implement a ventilator liberation protocol. (Quality of evidence: HIGH) | Maintain and improve physical conditioning. | 1 Provide early exercise and mobilization. (Quality of evidence: MODERATE) | Elevate the head of the bed to 30°–45°. (Quality of evidence: LOW) | Provide oral care with toothbrushing but without chlorhexidine. (Quality of evidence: MODERATE) | Provide early enteral rather than parenteral nutrition. (Quality of evidence: HIGH) | Maintain ventilator circuits. | 1 Change the ventilator circuit only if visibly soiled or malfunctioning (or per manufacturers’ instructions) (Quality of evidence: HIGH). | Additional approaches | May decrease duration of mechanical ventilation, length of stay, and/or mortality in some populations but not in others, and they may confer some risk of harm | in some populations. | 1 Consider using selective decontamination of the oropharynx and digestive tract to decrease microbial burden in ICUs with low prevalence of antibiotic | resistant organisms. Antimicrobial decontamination is not recommended in countries, regions, or ICUs with high prevalence of antibiotic-resistant | organisms. (Quality of evidence: HIGH) | Additional approaches | May lower VAP rates, but current data are insufficient to determine their impact on duration of mechanical ventilation, length of stay, and mortality. | 1 Consider using endotracheal tubes with subglottic secretion drainage ports to minimize pooling of secretions above the endotracheal cuff in patients | likely to require >48–72 hours of intubation. (Quality of evidence: MODERATE) | 2 Consider early tracheostomy. (Quality of evidence: MODERATE) | 3 Consider postpyloric feeding tube placement in patients with gastric feeding intolerance at high risk for aspiration. (Quality of evidence: MODERATE) | 6 Deborah S. Yokoe et al | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Preterm neonatal patients | Pediatric patients | Essential practices | Confer minimal risk of harm and may lower VAP and/or PedVAE rates. | Avoid intubation. (Quality of evidence: HIGH) | Minimize duration of mechanical ventilation. (Quality of evidence: HIGH) | 1 Manage patients without sedation whenever possible. (Quality of evidence: LOW) | 2 Use caffeine therapy for apnea of prematurity within 72 hours after birth to facilitate extubation. (Quality of evidence: HIGH) | 3 Assess readiness to extubate daily. (Quality of evidence: LOW) | 4 Take steps to minimize unplanned extubation and reintubation. (Quality of evidence: LOW) | 5 Provide regular oral care with sterile water (extrapolated from practice in infants and children, no data in preterm neonates). (Quality of evidence: | LOW) | 6 Change the ventilator circuit only if visibly soiled or malfunctioning or according to the manufacturer’s instructions for use (extrapolated from studies in | adults and children, no data in preterm neonates). (Quality of evidence: LOW) | Additional approaches | Minimal risks of harm, but impact on VAP and VAE rates is unknown. | 1 Lateral recumbent positioning. (Quality of evidence: LOW) | 2 Reverse Trendelenberg positioning. (Quality of evidence: LOW) | 3 Closed or in-line suctioning. (Quality of evidence: LOW) | 4 Oral care with maternal colostrum. (Quality of evidence: MODERATE) | Essential practices | Confer minimal risk of harm and some data suggest that they may lower VAP rates, PedVAE rates, and/or duration of mechanical ventilation. | Avoid intubation. | 1 Use noninvasive positive pressure ventilation (NIPPV) or high-flow oxygen by nasal cannula whenever safe and feasible. (Quality of evidence: | MODERATE) | Minimize duration of mechanical ventilation. | 1 Assess readiness to extubate daily using spontaneous breathing trials in patients without contraindications. (Quality of evidence: MODERATE) | 2 Take steps to minimize unplanned extubations and reintubations. (Quality of evidence: LOW) | 3 Avoid fluid overload. (Quality of evidence: MODERATE) | Provide regular oral care (ie, toothbrushing or gauze if no teeth). (Quality of evidence: LOW) | Elevate the head of the bed unless medically contraindicated. (Quality of evidence: LOW) | Maintain ventilator circuits. | 1 Change ventilator circuits only when visibly soiled or malfunctioning (or per manufacturer’s instructions). (Quality of evidence: MODERATE) | 2 Remove condensate from the ventilator circuit frequently and avoid draining the condensate toward the patient. (Quality of evidence: LOW) | Endotracheal tube selection and management | 1 Use cuffed endotracheal tubes. (Quality of evidence: LOW) | 2 Maintain cuff pressure and volume at the minimal occlusive settings to prevent clinically significant air leaks around the endotracheal tube, typically | 20-25cm H2O. This “minimal leak” approach is associated with lower rates of post-extubation stridor. (Quality of evidence: LOW) | 3 Suction oral secretions before each position change. (Quality of evidence: LOW) | Additional approaches | Minimal risks of harm and some evidence of benefit in adult patients but data in pediatric populations are limited. | 1 Minimize sedation. (Quality of evidence: MODERATE) | 2 Use endotracheal tubes with subglottic secretion drainage ports for patients ≥10 years of age. (Quality of evidence: LOW) | 3 Consider early tracheostomy. (Quality of evidence: LOW) | Infection Control & Hospital Epidemiology 7 | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Strategies to prevent nonventilator hospital-acquired pneumonia (NV-HAP) | Strategies to prevent healthcare-associated infections through hand hygiene | Essential practices | Promote the maintenance of healthy hand skin and nails. (Quality of evidence: HIGH) | 1 Promote the preferential use of alcohol-based hand sanitizer (ABHS) in most clinical situations. (Quality of evidence: HIGH) | 2 Perform hand hygiene as indicated by CDC or the WHO Five Moments. (Quality of evidence: HIGH) | 3 Include fingernail care in facility-specific policies related to hand hygiene. (Quality of evidence: HIGH) | a) Healthcare personnel (HCP) should maintain short, natural fingernails. | b) Nails should not extend past the fingertip. | c) HCP who provide direct or indirect care in high-risk areas | (eg, ICU or perioperative) should not wear artificial fingernail extenders. | d) Prohibitions against fingernail polish (standard or gel shellac) are at the discretion of the infection prevention program, except among scrubbed | individuals who interact with the sterile field during surgical procedures; these individuals should not wear fingernail polish or gel shellac. | 4 Engage all HCP in primary prevention of occupational irritant and allergic contact dermatitis. (Quality of evidence: HIGH) | 5 Provide cotton glove liners for HCP with hand irritation and educate these HCP on their use. (Quality of evidence: MODERATE) | Select appropriate products. | 1 For routine hand hygiene, choose liquid, gel, or foam ABHS with at least 60% alcohol. (Quality of evidence: HIGH) | 2 Involve HCP in selection of products. (Quality of evidence: HIGH) | 3 Obtain and consider manufacturers’ product-specific data if seeking ABHS with ingredients that may enhance efficacy against organisms anticipated to | be less susceptible to biocides. (Quality of evidence: MODERATE) | 4 Confirm that the volume of ABHS dispensed is consistent with the volume shown to be efficacious. (Quality of evidence: HIGH) | 5 Educate HCP about an appropriate volume of ABHS and the time required to obtain effectiveness. (Quality of evidence: HIGH) | 6 Provide facility-approved hand moisturizer that is compatible with antiseptics and gloves. (Quality of evidence: HIGH) | 7 For surgical antisepsis, use an FDA-approved surgical hand scrub or waterless surgical hand rub. (Quality of evidence: HIGH) | Ensure the accessibility of hand hygiene supplies. (Quality of evidence: HIGH) | 1 Ensure ABHS dispensers are unambiguous, visible, and accessible within the workflow of HCP. (Quality of evidence: HIGH) | 2 In private rooms, consider 2 ABHS dispensers the minimum threshold for adequate numbers of dispensers: 1 dispenser in the hallway, and 1 in the | patient room. (Quality of evidence: HIGH) | 3 In semiprivate rooms, suites, bays, and other multipatient bed configurations, consider 1 dispenser per 2 beds the minimum threshold for adequate | numbers of dispensers. Place ABHS dispensers in the workflow of HCP. (Quality of evidence: LOW) | 4 Ensure that the placement of hand hygiene supplies (eg, individual pocket-sized dispensers, bed mounted ABHS dispenser, single use pump bottles) is | easily accessible for HCP in all areas where patients receive care. (Quality of evidence: HIGH) | 5 Evaluate for the risk of intentional consumption. Utilize dispensers that mitigate this risk, such as wall-mounted dispensers that allow limited numbers | of activations within short periods (eg, 5 seconds). (Quality of evidence: LOW) | 6 Have surgical hand rub and scrub available in perioperative areas. (Quality of evidence: HIGH) | 7 Consider providing ABHS hand rubs or handwash with FDA-approved antiseptics for use in procedural areas and prior to high-risk bedside procedures | (eg, central-line insertion). (Quality of evidence: LOW) | (Continued) | Practices supported by interventional studies suggesting lower | NV-HAP rates | 1 Provide regular oral care. | 2 Diagnose and manage dysphagia. | 3 Provide early mobilization. | 4 Implement multimodal interventions to prevent viral infections. | 5 Use prevention bundles. | 8 Deborah S. Yokoe et al | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Implementing strategies to prevent healthcare-associated infections | Standard approach to implementation | Examples of implementation frameworks | (Continued ) | Ensure appropriate glove use to reduce hand and environmental contamination. (Quality of Evidence: HIGH) | 1 Use gloves for all contact with the patient and environment as indicated by standard and contact precautions during the care of individuals with | organisms confirmed to be less susceptible to biocides (e.g., C. difficile or norovirus) | 2 Educate HCP about the potential for self-contamination and environmental contamination when gloves are worn. (Quality of evidence: HIGH) | 3 Educate and confirm the ability of HCP to doff gloves in a manner that avoids contamination. (Quality of evidence: HIGH) | Take steps to reduce environmental contamination associated with sinks and sink drains. (Quality of evidence: HIGH) | Monitor adherence to hand hygiene. (Quality of evidence: HIGH) | Provide timely and meaningful feedback to enhance a culture of safety. (Quality of evidence: MODERATE) | Additional approaches during outbreaks | 1 Consider educating HCP using a structured approach (eg, WHO Steps) for handwashing or hand sanitizing. Evaluate HCP adherence to technique. | (Quality of evidence: LOW) | 2 For waterborne pathogens of premise plumbing, consider disinfection of sink drains using an EPA-registered disinfectant with claims against biofilms. | Consult with state or local public health for assistance in determining appropriate protocols for use and other actions needed to ensure safe supply. | (Quality of evidence: LOW) | 3 For C. difficile and norovirus, in addition to contact precautions, encourage hand washing with soap and water after the care of patients with known or | suspected infections. (Quality of evidence: LOW) | 1 Assess determinants of change and | classify as follows: | • Facilitators: promote practice or | change, or | • Barriers: hinder practice or change | Individual level: healthcare personnel, leaders, patients, and visitors’ preferences, needs, attitudes, and | knowledge. | Facility level: team composition, communication, culture, capacity, policies, resources. | Partners: degree of support and buy-in. | 2 Choose measures Measurement methods must be appropriate for the question(s) they seek to answer and adhere to the | methods’ data collection and analysis rules: | • Outcome measure: ultimate goal (eg, HAI reduction). | • Process measure: action reliability (eg, bundle adherence). | • Balancing measure: undesired outcome of change (eg, staff absences due to required vaccine side effects). | 3 Select framework(s) See below and “Implementing Strategies to Prevent Infections in Acute Care Settings” (Table 3) | 32 | Framework Published Experience Resources | 4Es Settings | • Healthcare facilities | • Large-scale projects including multiple | sites | Infection prevention and control | • HAI prevention (including mortality | reduction and cost savings) | • 4Es Framework11 | • HAI reduction12–14 | • Mortality reduction15 | • Cost savings16 | Behavior Change Wheel Settings | • Community-based practice | • Healthcare facilities | Healthy behaviors | • Smoking cessation | • Obesity prevention | • Increased physical activity | Infection prevention and control | • Hand hygiene adherence | • Antibiotic prescribing17 | • Behavior Change Wheel: A Guide to Designing Interventions18 | • Stand More at Work (SMArT Work)19 | (Continued) | Infection Control & Hospital Epidemiology 9 | https://doi.org/10.1017/ice.2023.138 Published online by Cambridge University Press | Acknowledgments. The Compendium Partners thank the authors for their | dedication to this work, including maintaining adherence to the rigorous | process for the development of the Compendium: 2022 Updates, involving but | not limited to screening of thousands of articles; achieving multilevel consensus; | and consideration of, response to, and incorporation of many organizations’ | feedback and comments. We acknowledge these efforts especially because they | occurred as the authors handled the demands of the COVID-19 pandemic. The | authors thank Valerie Deloney, MBA, for her organizational expertise in the | development of this manuscript and Janet Waters, MLS, BSN, RN, for her | expertise in developing the strategies used for the literature searches that | informed this manuscript. The authors thank the many individuals and | organizations who gave their time and expertise to review and provide | (Continued ) | Comprehensive Unit-based | Safety Program (CUSP) | Settings | • Intensive care units | • Ambulatory centers | Improvements | • Antibiotic prescribing | • CLABSI prevention | • CAUTI prevention | • CUSP Implementation Toolkit20 | • AHA/HRET: Eliminating CAUTI (Stop CAUTI)21 | • AHRQ Toolkit to Improve Safety in Ambulatory Surgery Centers22 | European Mixed Methods Settings | • European institutions of varied | healthcare systems and cultures | Improvements: | • CLABSI prevention | • Hand hygiene | • PROHIBIT: Description and Materials23 | Getting to Outcomes (GTO)® Settings | • Community programs and services | Improvements | • Sexual health promotion | • Dual-disorder treatment program in | veterans | • Community emergency preparedness | • RAND Guide for Emergency Preparedness24 (illustrated overview of GTO® methodology) | Model for Improvement Settings | • Healthcare (inpatient, perioperative, | ambulatory) | • Public health | Interventions | • PPE use | • HAI prevention | • Public health process evaluation | • Institute for Healthcare Improvement25 | • The Improvement Guide26 | • Deming’s System of Profound Knowledge27 | Reach, Effectiveness, Adoption, | Implementation, Maintenance | (RE-AIM) | Settings | • Healthcare | • Public health | • Community programs | • Sexual health | Evaluations | • Antimicrobial stewardship in the ICU | • Clinical practice guidelines for STIs | • Promotion of vaccination | • Implementation of contact tracing | • RE-AIM.org28 | • Understanding and applying the RE-AIM framework: Clarifications and | resources29 | Replicating Effective Practices | (REP) | Settings | • Healthcare | • Public health | • HIV prevention | Interventions that have produced | positive results are reframed for local | relevance | CDC Compendium of HIV Prevention Interventions with Evidence of | Effectiveness30 (see Section C, Intervention Checklist) | Theoretical Domains Settings | • Healthcare (inpatient, perioperative, | ambulatory) | • Community (individual and communitybased behaviors) | Health maintenance | • Diabetes management in primary care | • Pregnancy weight management | HCP practice | • ICU blood transfusion | • Selective GI tract decontamination | • Preoperative testing | • Spine imaging | • Hand hygiene

Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request.

The control of pandemic pathogens depends on early prediction of pandemic variants and, more generally, understanding origins of such variants and factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of millions of annual gastroenteritis cases. Previous studies have suggested that new GII.4 pandemic viruses evolve from previous pandemic variants through substitutions in the antigenic region of the VP1 protein that enable evasion of host population immunity, leading to global spread. In contrast, we show here that the acquisition of new genetic and antigenic characteristics is not the proximal driver of new pandemics. Instead, pandemic GII.4 viruses circulate undetected for years before causing a new pandemic, during which time they diversify and spread over wide geographical areas. Serological data demonstrate that by 2003, some nine years before it emerged as a new pandemic, the ancestral 2012 pandemic strain had already acquired the antigenic characteristics that allowed it to evade prevailing population immunity against the previous 2009 pandemic variant. These results provide strong evidence that viral genetic changes are necessary but not sufficient for GII.4 pandemic spread. Instead, we suggest that it is changes in host population immunity that enable pandemic spread of an antigenically-preadapted GII.4 variant. These results indicate that predicting future GII.4 pandemic variants will require surveillance of currently unsampled reservoir populations. Furthermore, a broadly acting GII.4 vaccine will be critical to prevent future pandemics.Significance Norovirus pandemics and their associated public health and economic costs could be prevented by effective vaccines. However, vaccine development and distribution will require identification of the sources and drivers of new pandemics. We here use phylogenetics and serological experiments to develop and test a new hypothesis of pandemic norovirus emergence. We find that pandemic noroviruses preadapt, diversify and spread worldwide years prior to emergence, strongly indicating that genetic changes are necessary but not sufficient to drive a new pandemic. We instead suggest that changes in population immunity enable pandemic emergence of a pre-adapted low-level variant. These findings indicate that prediction of new pandemics will require surveillance of under-sampled virus reservoirs and that norovirus vaccines will need to elicit broad immunity.

Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective(s): To evaluate the quantitative titers and durability of binding antibodies detected after SARSCoV-2 infection and subsequent COVID-19 vaccination. Design(s): A prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOWTM COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. Setting(s): A nursing home during and after a SARS-CoV-2 outbreak. Participant(s): 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-CoV-2 testing (BinaxNOWTM, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). Result(s): Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation <=90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Conclusions and Relevance: Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

BACKGROUND: The diagnosis of SARS-CoV-2-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute COVID-19 and may impact clinical management. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at six academic medical centers during March 1, 2020-December 31, 2021. MIS-A patients were matched on age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10,223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched COVID-19 patients, MIS-A patients were more likely to be non-Hispanic Black and less likely to be non-Hispanic White. MIS-A patients more likely had laboratory-confirmed COVID-19 ≥ 14 days prior to hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, MIS-A patients had higher neutrophil-to-lymphocyte ratio, C-reactive protein, ferritin, procalcitonin and D-dimer, compared with COVID-19 patients. MIS-A patients had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. Mortality was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management.

BACKGROUND: Population-based cancer survival provides insight into the effectiveness of health systems to care for all residents with cancer, including those in marginalized groups. METHODS: Using CONCORD-2 data, we estimated 5-year net survival among patients diagnosed 2004-2009 with one of 10 common cancers, and children diagnosed with acute lymphoblastic leukemia (ALL), by socioeconomic status (SES) quintile, age (0-14, 15-64, ≥65 years), and country (Canada or United States). RESULTS: In the lowest SES quintile, survival was higher among younger Canadian adults diagnosed with liver (23% vs 15%) and cervical (78% vs 68%) cancers and with leukemia (62% vs 56%), including children diagnosed with ALL (92% vs 86%); and higher among older Americans diagnosed with colon (62% vs 56%), female breast (87% vs 80%), and prostate (97% vs 85%) cancers. In the highest SES quintile, survival was higher among younger Americans diagnosed with stomach cancer (33% vs 27%) and younger Canadians diagnosed with liver cancer (31% vs 23%); and higher among older Americans diagnosed with stomach (27% vs 22%) and prostate (99% vs 92%) cancers. CONCLUSIONS: Among younger Canadian cancer patients in the lowest SES group, greater access to health care may have resulted in higher cancer survival, while higher screening prevalence and access to health insurance (Medicare) among older Americans during the period of this study may have resulted in higher survival for some screen-detected cancers. Higher survival in the highest SES group for stomach and liver may relate to treatment differences. Survival differences by age and SES between Canada and the United States may help inform cancer control strategies.

In October 2022, the Southern Nevada Health District (SNHD) was notified of a higher-than-expected number of pediatric patients hospitalized with intracranial abscesses; similar concerns were previously reported nationally (1,2). This rare infection is associated with significant morbidity (3,4). When SNHD received the report in October 2022, 14 cases had been diagnosed in the largest pediatric hospital in southern Nevada. SNHD investigated the reported increase to confirm that a cluster had been detected, identify common risk factors for infection, report findings to the community, and recommend measures to prevent future cases.

Increases in mental health conditions have been documented among the general population and health care workers since the start of the COVID-19 pandemic (1-3). Public health workers might be at similar risk for negative mental health consequences because of the prolonged demand for responding to the pandemic and for implementing an unprecedented vaccination campaign. The extent of mental health conditions among public health workers during the COVID-19 pandemic, however, is uncertain. A 2014 survey estimated that there were nearly 250,000 state and local public health workers in the United States (4). To evaluate mental health conditions among these workers, a nonprobability-based online survey was conducted during March 29-April 16, 2021, to assess symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal ideation among public health workers in state, tribal, local, and territorial public health departments. Among 26,174 respondents, 52.8% reported symptoms of at least one mental health condition in the preceding 2 weeks, including depression (30.8%), anxiety (30.3%), PTSD (36.8%), or suicidal ideation (8.4%). The highest prevalence of symptoms of a mental health condition was among respondents aged ≤29 years (range = 13.6%-47.4%) and transgender or nonbinary persons (i.e., those who identified as neither male nor female) of all ages (range = 30.4%-65.5%). Public health workers who reported being unable to take time off from work were more likely to report adverse mental health symptoms. Severity of symptoms increased with increasing weekly work hours and percentage of work time dedicated to COVID-19 response activities. Implementing prevention and control practices that eliminate, reduce, and manage factors that cause or contribute to public health workers' poor mental health might improve mental health outcomes during emergencies.

INTRODUCTION: We developed a standardized method, "Possible poor treatment response" (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary TB. We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcome for all participants were achieved. METHODS/DESIGN: A PPTR event was defined as the occurrence of one or more pre-specified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. RESULTS: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 weeks). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome, and between 13.8 and 14.7% of participants with favorable and not assessable outcomes. 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve disease-free cure. DISCUSSION: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772.

On May 17, 2022, the Massachusetts Department of Health announced the first suspected case of monkeypox associated with the global outbreak in a U.S. resident. On May 23, 2022, CDC launched an emergency response (1,2). CDC's emergency response focused on surveillance, laboratory testing, medical countermeasures, and education. Medical countermeasures included rollout of a national JYNNEOS vaccination strategy, Food and Drug Administration (FDA) issuance of an emergency use authorization to allow for intradermal administration of JYNNEOS, and use of tecovirimat for patients with, or at risk for, severe monkeypox. During May 17-October 6, 2022, a total of 26,384 probable and confirmed* U.S. monkeypox cases were reported to CDC. Daily case counts peaked during mid-to-late August. Among 25,001 of 25,569 (98%) cases in adults with information on gender identity,(†) 23,683 (95%) occurred in cisgender men. Among 13,997 cisgender men with information on recent sexual or close intimate contact,(§) 10,440 (75%) reported male-to-male sexual contact (MMSC) ≤21 days preceding symptom onset. Among 21,211 (80%) cases in persons with information on race and ethnicity,(¶) 6,879 (32%), 6,628 (31%), and 6,330 (30%) occurred in non-Hispanic Black or African American (Black), Hispanic or Latino (Hispanic), and non-Hispanic White (White) persons, respectively. Among 5,017 (20%) cases in adults with information on HIV infection status, 2,876 (57%) had HIV infection. Prevention efforts, including vaccination, should be prioritized among persons at highest risk within groups most affected by the monkeypox outbreak, including gay, bisexual, and other men who have sex with men (MSM); transgender, nonbinary, and gender-diverse persons; racial and ethnic minority groups; and persons who are immunocompromised, including persons with advanced HIV infection or newly diagnosed HIV infection.

There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. We conducted a prospective longitudinal evaluation of 11 consenting SARS-CoV-2-positive nursing home residents to evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. The evaluation included nine visits over 150 days from October 25, 2020, through April 1, 2021. Visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW™ COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. We evaluated quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). The median age among participants was 74 years; one participant was immunocompromised. Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies, and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive, but none were culture- positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation ≤90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

PURPOSE: Inadequate pre-enlistment physical activity is a risk factor for musculoskeletal injury during and discharge from basic military training. We estimated the prevalence of physical activity (PA) participation among the US population eligible to enter the armed forces based on age and body mass index (BMI) overall and by selected characteristics. | | METHODS: Data on non-pregnant, age-eligible respondents (aged 17-42 years) were analyzed from the January 2015 - March 2020 National Health and Nutrition Examination Survey (unweighted n = 5964). In accordance with Department of Defense policy, BMI eligibility was defined as 19.0-27.5 kg/m2; BMI was calculated from measured weight and height. Based on guidance from the US Army Pre-Basic Combat Training Physical Training Program and the Physical Activity Guidelines for Americans, 2nd edition, we characterized inadequate PA participation as < 300 minutes/week of equivalent moderate-intensity PA from all domains. We calculated PA overall and compared PA by gender, age, race/ethnicity, education, and family income using the Satterthwaite adjusted F-test. | | RESULTS: Of the age-eligible population, 47.3% were BMI eligible. Among those eligible by age and BMI, 27.5% had an inadequate PA level. Prevalence of inadequate PA was lower among males than females (P = .001) and non-Hispanic white persons versus other racial/ethnic groups (P < .001); no significant differences were evident by age, education, or family income. Among those with BMI < 19.0 kg/m2 and > 27.5 kg/m2, respective prevalence of inadequate PA was 36.3% and 36.5%. | | CONCLUSIONS: Less than half of the military age-eligible US population has an eligible BMI for entering the US armed forces. Over a quarter of these report PA that may be inadequate for basic military training. Promotion of healthy weight status and participation in PA in young adults could help improve readiness to enter the armed forces.

BACKGROUND: Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 non-inferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had non-inferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the pre-specified subgroup of people with HIV (PWH). METHODS: PWH and CD4 + counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months post-randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% non-inferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV-status. PWH were enrolled in a staged fashion, to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz. RESULTS: 2,516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4 + count was 344 cells/μL (interquartile range: 223-455). The rifapentine-moxifloxacin regimen was non-inferior to control (absolute difference in unfavorable outcomes -7.4% [95% CI -20.8% to +6.0%]); the rifapentine regimen was not non-inferior to control (+7.5% [95% CI -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%). CONCLUSIONS: In people with HIV-associated DS-PTB with CD4 + counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was non-inferior to the 6-month control regimen and was safe.

In recent decades, national estimates have demonstrated growing childhood asthma disparities.1, 2 But this birds’ eye view could not clearly identify underlying causes or remedies needed at the complicated ground level. In this issue of Pediatrics, Tyris et al.,3 in their study of adverse asthma outcomes among children in Washington, DC, marry two innovations—use of at-risk rates to measure asthma outcomes and assessment of social determinants of health (SDOH) at the census tract level—to reveal aspects of disparities that can inform actions to address them.

PURPOSE: To evaluate the association between risk factors, mitigating factors, and adverse mental health outcomes among United States public health workers. METHODS: Cross-sectional online survey data were collected March to April 2021. The survey was distributed to public health workers who worked in a state, tribal, local, or territorial public health department since March 2020. RESULTS: In total, 26,174 United States state and local public health workers completed the survey. Feeling isolated was a risk factor for anxiety (PR, 1.84; 95% CI, 1.74-1.95), depression (PR, 1.84; 95% CI, 1.75-1.94), post-traumatic stress disorder (PR, 1.50; 95% CI, 1.43-1.57), and suicidal ideation (PR, 3.23; 95% CI, 2.82-3.69). The ability to take time off was linked to fewer reported symptoms of anxiety (PR, 0.87; 95% CI, 0.83-0.90), depression (PR, 0.86; 95% CI, 0.83-0.89), post-traumatic stress disorder (PR, 0.84; 95% CI, 0.81-0.88), and suicidal ideation (PR, 0.84; 95% CI, 0.77-0.92). CONCLUSIONS: Since COVID-19 was declared a pandemic, respondents who felt isolated and alone were at an increased risk for adverse mental health outcomes. Findings from this study call for public health organizations to provide their workforce with services and resources to mitigate adverse mental health outcomes.

Background: Burkholderia pseudomallei is a Tier 1 overlap select agent and subject to the select agent regulations (42 CFR §73 and 9 CFR §121). It is a gram-negative, motile, soil saprophyte, and the etiologic agent of melioidosis. B. pseudomallei infection can produce systemic illness and can be fatal in the absence of appropriate treatment. Laboratory exposures involving this organism may occur when appropriate containment measures are not employed. Current disease treatment inadequacies and the risk factors associated with melioidosis make this an agent of primary concern in research, commercial, and clinical laboratory environments. Results: This study presents data reported to Centers for Disease Control and Prevention (CDC), Division of Select Agents and Toxins for releases involving B. pseudomallei in 2017-2019 that occurred in Biosafety Level (BSL)-2 and BSL-3 laboratories. Fifty-one Animal and Plant Health Inspection Service (APHIS)/CDC Form 3 release reports led to the medical surveillance of 275 individuals. Entities offered post-exposure prophylaxis to ?76% of the individuals impacted in the presented events. Summary: Laboratory safety can be improved by implementing appropriate safety precautions to minimize exposures. Most of the incidents discussed in this evidence-based report occurred during work conducted in the absence of primary containment. None of the releases resulted in illness, death, or transmission to or among workers, nor was there transmission outside of a laboratory into the surrounding environment or community. Effective risk assessment and management strategies coupled with standard and special microbiological policies and procedures can result in reduced exposures and improved safety at facilities. © Copyright 2022, ABSA International 2022 2022.

Crimean-Congo hemorrhagic fever (CCHF) is a highly fatal zoonotic disease endemic to Kazakhstan. Previous work estimated the seroprevalence of CCHF virus (CCHFV) among livestock owners in the Zhambyl region of southern Kazakhstan at 1.2%. To estimate CCHFV seroprevalence among cattle and sheep, we selected 15 villages with known history of CCHFV circulation (endemic) and 15 villages without known circulation (nonendemic) by cluster sampling with probability proportional to livestock population size. We collected whole blood samples from 521 sheep and 454 cattle from randomly selected households within each village and collected ticks found on the animals. We tested livestock blood for CCHFV-specific IgG antibodies by ELISA; ticks were screened for CCHFV RNA by real-time reverse transcription polymerase chain reaction and CCHFV antigen by antigen-capture ELISA. We administered questionnaires covering animal demographics and livestock herd characteristics to an adult in each selected household. Overall weighted seroprevalence was 5.7% (95% CI: 3.1, 10.3) among sheep and 22.5% (95% CI: 15.8, 31.2) among cattle. CCHFV-positive tick pools were found on two sheep (2.4%, 95% CI: 0.6, 9.5) and three cattle (3.8%, 95% CI: 1.2, 11.5); three CCHFV-positive tick pools were found in nonendemic villages. Endemic villages reported higher seroprevalence among sheep (15.5% versus 2.8%, P < 0.001) but not cattle (25.9% versus 20.1%, P = 0.42). Findings suggest that the current village classification scheme may not reflect the geographic distribution of CCHFV in Zhambyl and underscore that public health measures must address the risk of CCHF even in areas without a known history of circulation.