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Background: Greater than 10% of hospitalized MRSA carriers experience serious MRSA infection in the year following discharge. Prevention opportunities have primarily focused on hospital stays; however postdischarge interventions have the potential to reduce morbidity, mortality and healthcare costs. The CLEAR trial found a 30% hazard reduction in postdischarge MRSA infections among patients who had inpatient MRSA cultures and were given postdischarge decolonization (5 days twice-a-month for 6 months) relative to hygiene education alone. We conducted a cost analysis of the CLEAR intervention to quantify the economic implications and understand the value of adopting this MRSA decolonization strategy. Methods: We constructed a decision model to estimate the one-year healthcare utilization and costs associated with postdischarge decolonization relative to hygiene education. Trial results for MRSA infection risk and downstream outcomes (including outpatient and emergency room visits, hospitalizations, related nursing home stays, and postdischarge antibiotics) were used to parameterize the model. Other medical care and prescription drug costs were based on Medicare Fee Schedules, Red Book and the literature. Patient out-of-pocket costs and time costs associated with subsequent infections were from a survey of trial participants experiencing infection (n=405). All costs were reported in 2019 US dollars. The analysis was conducted using healthcare system and societal perspectives. Sensitivity analyses were conducted on key parameters. Results: Among a hypothetical cohort of 1,000 hospitalized MRSA carriers, we estimated that a postdischarge decolonization intervention versus hygiene education would result in at least 36 fewer subsequent MRSA infections (130 vs 93 of 1,000, respectively) and >40 fewer MRSA-attributable healthcare events including 32 hospitalizations and 6 postdischarge nursing home visits over the course of a year. Assuming an intervention cost of $185 per individual, the program would result in an overall cost savings of $469,000 per 1,000 MRSA carriers undergoing decolonization. This translates to an overall savings of $13,200 per infection averted and $9,000 per infection averted from the healthcare system perspective. Even assuming a lower infection rate or a less effective intervention (15% reduction in infections vs 30% in the CLEAR trial), or a more expensive (up to $653 per patient) intervention, a decolonization program would still result in cost-savings for society, the healthcare system and patients. Conclusions: In addition to health benefits of preventing infections, postdischarge decolonization of MRSA carriers yields substantial savings to society and the healthcare system. Future recommendations for reducing postdischarge MRSA-related disease among MRSA carriers should consider routine decolonization at hospital discharge. Funding: This study was supported by a grant from the AHRQ Healthcare-Associated Infections Program (R01HS019388) and by the University of California Irvine Institute for Clinical and Translational Science, which was funded by a grant from the NIH Clinical and Translational Sciences Award program (UL1 TR000153). Disclosures: Dr. Huang reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), Mölnlycke, 3M, Clorox, Xttrium Laboratories, and Medline. Ms. Singh reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline. Dr. Rashid, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker(Sage Products), Clorox, and Medline. Dr. McKinnell reports receiving grant support to his institution from Melinta Therapeutics, and fees for serving as a research investigator from Lightship, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories and Medline, and serving as cofounder of Expert Stewardship. Dr. Miller reports receiving grant support from Gilead Sciences, Merck, Abbott, Cepheid, Genentech, Atox Bio, and Paratek Pharmaceuticals, grant support and fees for serving on an advisory board from Achaogen and grant support, consulting fees, and fees for serving on an advisory board from Tetraphase and conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline.

Pediatric sepsis is a major public health concern, and robust surveillance tools are needed to characterize its incidence, outcomes, and trends. The increasing use of electronic health records (EHRs) in the United States creates an opportunity to conduct reliable, pragmatic, and generalizable population-level surveillance using routinely collected clinical data rather than administrative claims or resource-intensive chart review. In 2015, the US Centers for Disease Control and Prevention recruited sepsis investigators and representatives of key professional societies to develop an approach to adult sepsis surveillance using clinical data recorded in EHRs. This led to the creation of the adult sepsis event definition, which was used to estimate the national burden of sepsis in adults and has been adapted into a tool kit to facilitate widespread implementation by hospitals. In July 2018, the Centers for Disease Control and Prevention convened a new multidisciplinary pediatric working group to tailor an EHR-based national sepsis surveillance approach to infants and children. Here, we describe the challenges specific to pediatric sepsis surveillance, including evolving clinical definitions of sepsis, accommodation of age-dependent physiologic differences, identifying appropriate EHR markers of infection and organ dysfunction among infants and children, and the need to account for children with medical complexity and the growing regionalization of pediatric care. We propose a preliminary pediatric sepsis event surveillance definition and outline next steps for refining and validating these criteria so that they may be used to estimate the national burden of pediatric sepsis and support site-specific surveillance to complement ongoing initiatives to improve sepsis prevention, recognition, and treatment.

Background: Neutrophils in sickle cell disease (SCD) are activated, contributing to disease. Red cell exchange (RCE), with the goal of lowering hemoglobin S (HbS), is an important part of therapy for many SCD patients. Whether RCE impacts neutrophil reactivity is unknown. Study Design and Methods: To determine the effect of RCE on neutrophil activation, SCD patients undergoing RCE in steady‐state were enrolled. Neutrophil degranulation responses were examined before/after RCE. Kinetic studies were completed to determine the duration of the effect of RCE on neutrophil function. Degranulation results were examined in relation to white blood cell count, neutrophil count, and HbS levels. The effect of RCE on RBC phosphatidylserine (PS) exposure was examined as a possible contributor to modulation of neutrophil function by RCE. Results: Twenty‐two patients with SCD, genotype SS, who underwent RCE (average pre‐RCE HbS 33 ± 14%) were included for the study. RCE significantly decreased neutrophil degranulation responses. The effect of RCE on neutrophil activation was unrelated to cell count and instead directly correlated with HbS. The effect of RCE on neutrophil activation was sustained over several days post‐apheresis. Furthermore, while increased RBC PS exposure results in increased neutrophil degranulation, RCE decreases RBC PS exposure. Discussion: To our knowledge, this is the first study demonstrating that RCE significantly decreases neutrophil activation in a sustained HbS‐dependent manner. Modulation of PS exposure by RCE may be a contributing mechanism by which RCE modulates neutrophil activation. These studies raise the possibility that modulation of neutrophil activation contributes significantly to the therapeutic effect of RCE. See editorial on page 1593–1596, in this issue [ABSTRACT FROM AUTHOR]

Rates of invasive pneumococcal disease have declined since widespread introduction of pneumococcal conjugate vaccines (PCVs) in the United States. We evaluated the impact of immunization status and recent antibiotic use on an individual child's risk of colonization. This study extends previously reported data from children

Key Points: Question: Among patients with increased risk of postpartum venous thromboembolism, does a more selective protocol for initiating postpartum enoxaparin, compared with a standard risk-stratified protocol, decrease wound complications without increasing patient risk of venous thromboembolism? Findings: In this retrospective observational study, a more selective protocol for chemoprophylaxis resulted in a decrease in heparin (enoxaparin) administration (16% vs 8%). The selective protocol for postpartum enoxaparin was associated with a decrease in wound hematoma (0.7% vs 0.3% in the selective protocol group; adjusted odds ratio, 0.38; 95% CI, 0.21-0.67) without evidence of increase in venous thromboembolism (0.1% vs 0.1% in the selective protocol group; adjusted odds ratio, 0.40; 95% CI, 0.12-1.36). Meaning: A more selective protocol for postpartum enoxaparin was associated with decreased rates of wound hematomas without evidence of increased rates of postpartum thromboembolic events. Importance: In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists guidelines that recommended postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm. In response to increased wound hematomas without significant reduction in VTE using this protocol, a more selective risk-stratified approach was adopted in 2021. Objective: To evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol. Design, Setting, and Participants: Retrospective observational study of 17 489 patients who delivered at a single tertiary care center in the southeast US between January 1, 2016, and December 31, 2018 (original protocol), and between December 1, 2021, and May 31, 2023 (more selective protocol). Patients receiving outpatient anticoagulation for active VTE or high VTE risk during pregnancy were excluded. Exposure: Standard risk-stratified and more selective postpartum VTE chemoprophylaxis protocols. Main Outcomes and Measures: The primary outcome was clinical diagnosis of wound hematoma up to 6 weeks pos tpartum. The secondary outcome was new diagnosis of VTE up to 6 weeks post partum. We compared baseline characteristics and outcomes between groups and estimated adjusted odds ratios with 95% CIs of primary and secondary outcomes using the original protocol group as reference. Results: Of 17 489 patients included in the analysis, 12 430 (71%) were in the original protocol group and 5029 (29%) were in the more selective group. Rates of chemoprophylaxis decreased from 16% (original protocol) to 8% (more selective protocol). Patients in the more selective group were more likely to be older, be married, and have obesity or other comorbidities (hypertension, diabetes, cardiac disease). Compared with the original protocol, the more selective protocol was associated with a decrease in any wound hematoma (0.7% vs 0.3%; adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.67), specifically due to a lower rate of superficial wound hematomas (0.6% vs 0.3%; aOR, 0.43; 95% CI, 0.24-0.75). There was no significant increase in VTE or individual types of VTE (0.1% vs 0.1%; aOR, 0.40; 95% CI, 0.12-1.36). Conclusions and Relevance: A more selective risk-stratified approach to an enoxaparin thromboprophylaxis protocol for VTE was associated with decreased rates of wound hematomas without increased rates of postpartum VTE. This observational study assesses incidence of wound hematoma diagnoses up to 6 weeks post partum among obstetric patients who received thromboprophylaxis according to less selective vs more selective hospital chemoprophylaxis protocols. [ABSTRACT FROM AUTHOR]

Background Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions, such as coughing, and care activities, such as aerosol-generating procedures, likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of the personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. The purpose of the current study was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists, with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations, including 2 updated recommendations and 1 new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE by HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2, and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that can infect healthcare personnel (HCP) and patients in healthcare settings. Specific care activities, in particular, aerosol-generating procedures, may have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 has created significant challenges in healthcare facilities, particularly with severe shortages of personal protective equipment (PPE) used to protect HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care are needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. Objective Our objective was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel that included front-line clinicians, infectious diseases specialists, experts in infection control, and guideline methodologists with representation from the disciplines of preventive care, public health, medical microbiology, pediatrics, critical care medicine, and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then, a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations and provided narrative summaries of other interventions undergoing evaluations. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE for HCP who provide care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. Significant gaps in the understanding of the transmission dynamics of SARS-CoV-2 remain, and PPE recommendations may need to be modified in response to new evidence. [ABSTRACT FROM AUTHOR]

Healthcare personnel (HCP) represent a unique group of concern for transmission of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), the causative agent of coronavirus disease (COVID-19), because of their increased [...]

OBJECTIVE To create a national policy model to evaluate the projected cost-effectiveness of multiple hospital-based strategies to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission and infection. DESIGN Cost-effectiveness analysis using a Markov microsimulation model that simulates the natural history of MRSA acquisition and infection. PATIENTS AND SETTING Hypothetical cohort of 10,000 adult patients admitted to a US intensive care unit. METHODS We compared 7 strategies to standard precautions using a hospital perspective: (1) active surveillance cultures; (2) active surveillance cultures plus selective decolonization; (3) universal contact precautions (UCP); (4) universal chlorhexidine gluconate baths; (5) universal decolonization; (6) UCP + chlorhexidine gluconate baths; and (7) UCP+decolonization. For each strategy, both efficacy and compliance were considered. Outcomes of interest were: (1) MRSA colonization averted; (2) MRSA infection averted; (3) incremental cost per colonization averted; (4) incremental cost per infection averted. RESULTS A total of 1989 cases of colonization and 544 MRSA invasive infections occurred under standard precautions per 10,000 patients. Universal decolonization was the least expensive strategy and was more effective compared with all strategies except UCP+decolonization and UCP+chlorhexidine gluconate. UCP+decolonization was more effective than universal decolonization but would cost $2469 per colonization averted and $9007 per infection averted. If MRSA colonization prevalence decreases from 12% to 5%, active surveillance cultures plus selective decolonization becomes the least expensive strategy. CONCLUSIONS Universal decolonization is cost-saving, preventing 44% of cases of MRSA colonization and 45% of cases of MRSA infection. Our model provides useful guidance for decision makers choosing between multiple available hospital-based strategies to prevent MRSA transmission.

ObjectiveTo estimate and compare the impact on healthcare costs of 3 alternative strategies for reducing bloodstream infections in the intensive care unit (ICU): methicillin-resistant Staphylococcus aureus (MRSA) nares screening and isolation, targeted decolonization (ie, screening, isolation, and decolonization of MRSA carriers or infections), and universal decolonization (ie, no screening and decolonization of all ICU patients).DesignCost analysis using decision modeling.MethodsWe developed a decision-analysis model to estimate the health care costs of targeted decolonization and universal decolonization strategies compared with a strategy of MRSA nares screening and isolation. Effectiveness estimates were derived from a recent randomized trial of the 3 strategies, and cost estimates were derived from the literature.ResultsIn the base case, universal decolonization was the dominant strategy and was estimated to have both lower intervention costs and lower total ICU costs than either screening and isolation or targeted decolonization. Compared with screening and isolation, universal decolonization was estimated to save $171,000 and prevent 9 additional bloodstream infections for every 1,000 ICU admissions. The dominance of universal decolonization persisted under a wide range of cost and effectiveness assumptions.ConclusionsA strategy of universal decolonization for patients admitted to the ICU would both reduce bloodstream infections and likely reduce healthcare costs compared with strategies of MRSA nares screening and isolation or screening and isolation coupled with targeted decolonization.

BackgroundIn April 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 for use in the United States. We evaluated rates of pneumococcal colonization, by serotype and antibiotic resistance, in Massachusetts communities where serial cross-sectional surveillance has been conducted for the past decade.MethodsNasopharyngeal swabs were obtained from children 0 to

ObjectiveAntibiotic use rates have declined dramatically since the 1990s. We aimed to determine if, when, and at what level the decline in antibiotic-dispensing rates ended and which diagnoses contributed to the trends.MethodsAntibiotic dispensings and diagnoses were obtained from 2 health insurers for 3- to

BackgroundWe sought to measure trends in Streptococcus pneumoniae carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent 7-valent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent PCV (PCV13).MethodsWe conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children aged

Defining the propensity of Streptococcus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children ≤7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in 16 Massachusetts communities in 2003/04 and 8 of the 16 communities in both 2006/07 and 2008/09 were used to compute a serotype specific "invasive capacity (IC)" by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children of the same age. A total of 206 IPD and 806 NP isolates of SP were collected during the study period. An approximate 50-fold variation in the point estimates between the serotypes having the highest (18C, 33F, 7F, 19A, 3 and 22F) and lowest (6C, 23A, 35F, 11A, 35B, 19F, 15A, and 15BC) IC was observed. Point estimates of IC for most of the common serotypes currently colonizing children in Massachusetts were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes. Invasive capacity differs among serotypes and as new pneumococcal conjugate vaccines are introduced, ongoing surveillance will be essential to monitor whether serotypes with high invasive capacity emerge (e.g. 33F, 22F) as successful colonizers resulting in increased IPD incidence due to replacement serotypes.

BackgroundThe incidence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) has risen dramatically in the U.S., particularly among children. Although Streptococcus pneumoniae colonization has been inversely associated with S. aureus colonization in unvaccinated children, this and other risk factors for S. aureus carriage have not been assessed following widespread use of the heptavalent pneumococcal conjugate vaccine (PCV7). Our objectives were to (1) determine the prevalence of S. aureus and MRSA colonization in young children in the context of widespread use of PCV7; and (2) examine risk factors for S. aureus colonization in the post-PCV7 era, including the absence of vaccine-type S. pneumoniae colonization.MethodsSwabs of the anterior nares (S. aureus) were obtained from children enrolled in an ongoing study of nasopharyngeal pneumococcal colonization of healthy children in 8 Massachusetts communities. Children 3 months to

ObjectivesThe goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7).MethodsNasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to