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BACKGROUND The microbiologic etiologies, clinical manifestations, and antimicrobial treatment of neonatal infections differ substantially from infections in adult and pediatric patient populations. In 2019, the Centers for Disease Control and Prevention developed neonatal-specific (Standardized Antimicrobial Administration Ratios SAARs), a set of risk-adjusted antimicrobial use metrics that hospitals participating in the National Healthcare Safety Network’s (NHSN’s) antimicrobial use surveillance can use in their antibiotic stewardship programs (ASPs). METHODS The Centers for Disease Control and Prevention, in collaboration with the Vermont Oxford Network, identified eligible patient care locations, defined SAAR agent categories, and implemented neonatal-specific NHSN Annual Hospital Survey questions to gather hospital-level data necessary for risk adjustment. SAAR predictive models were developed using 2018 data reported to NHSN from eligible neonatal units. RESULTS The 2018 baseline neonatal SAAR models were developed for 7 SAAR antimicrobial agent categories using data reported from 324 neonatal units in 304 unique hospitals. Final models were used to calculate predicted antimicrobial days, the SAAR denominator, for level II neonatal special care nurseries and level II/III, III, and IV NICUs. CONCLUSIONS NHSN’s initial set of neonatal SAARs provides a way for hospital ASPs to assess whether antimicrobial agents in their facility are used at significantly higher or lower rates compared with a national baseline or whether an individual SAAR value is above or below a specific percentile on a given SAAR distribution, which can prompt investigations into prescribing practices and inform ASP interventions.

A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine®, iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3–4 log10 in 15–30 s in vitro. In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection., Tweetable abstract Commonly used antiseptics including povidone-iodine, Listerine®, iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate the progression and transmission of SARS-CoV-2.

The Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1’s potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1’s complex “time zero” definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA’s core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

Purpose Monitoring of procalcitonin (PCT) levels may support appropriate antibiotic discontinuation. The purpose of this study was to determine the current state of PCT monitoring at community hospitals across the United States. Methods Data from adult patients who were admitted to community hospitals affiliated with a large healthcare system between August 1, 2016, and July 31, 2017, and who received antibiotics were evaluated for the number of PCT levels drawn and the timing between multiple levels. Data from eligible patients were evaluated for the discontinuation of antibiotics after meeting prespecified PCT thresholds for discontinuation of therapy, namely, a PCT measurement of Results PCT levels were evaluated for 103,913 patient data sets collected from 136 hospitals. Of these, 70% of the data sets showed a single PCT level drawn, and approximately 30% (30,887) of the data sets showed multiple levels drawn. The first PCT measurement was drawn within 36 hours of antibiotic initiation in 96% of the patients. Of those with multiple levels, 23% (7,089) had levels drawn 24 to 72 hours apart. A small proportion (20% [6,127]) of the patients with multiple levels were eligible for evaluation of appropriate antibiotic discontinuation. Of these, 1,973 (32.2%) patients had antibiotics discontinued within 36 hours of meeting the prespecified PCT thresholds; these patients had a mean duration of antibiotic therapy of 6.1 days with a median of 4.7. Conclusion Additional standardization of ongoing PCT monitoring and education regarding the appropriate discontinuation of antibiotics when thresholds are reached could aid in the use of this biomarker in support of antibiotic and laboratory stewardship.

Background: Surgical site infections is one of the most common healthcare-associated infections. Staphylococcus aureus remains the most common etiologic agent causing surgical site infections. Studies confirm Staphylococcus aureus carriage increases the risk of Staphylococcus aureus surgical site infections. The purpose of this paper is to review the strategies to reduce surgical site infections due to Staphylococcus aureus focusing on nasal decolonization. Results: Published studies indicate screening patients for Staphylococcus aureus nasal carriage and decolonizing carriers during the preoperative period decreases the risk of S aureus surgical site infections in cardiac and orthopedic surgery. Most studies use combined chlorhexidene bathing and mupirocin for patients colonized with Staphylococcus aureus since colonization of multiple body sites is common and combination chlorhexidene bathing and intranasal mupirocin has been shown to be more effective at eradicating Staphylococcus aureus colonization. Mupirocin remains the best topical agent at eradicating nasal Staphylococcus aureus. Mupirocin has been shown to eliminate nasal colonization by over 90% with a five-day course, however, concerns over resistance have led to development of alternative agents. Nasal povidone-iodine, alcohol-based nasal antiseptic, and photodynamic therapy are promising new interventions, but more studies are needed. Conclusions: Short term nasal mupirocin is still the most studied and effective topical agent in eradicating Staphylococcus aureus nasal colonization. However, increasing mupirocin resistance remains an ongoing concern and newer agents are needed. Keywords: nasal decolonization, surgical site infections, mupirocin, healthcare-associated infections

Background The Centers for Medicare and Medicaid Services (CMS) use colon surgical site infection (SSI) rates to rank hospitals and apply financial penalties. The CMS’ risk-adjustment model omits potentially impactful variables that might disadvantage hospitals with complex surgical populations. Methods We analyzed adult patients who underwent colon surgery within facilities associated with HCA Healthcare from 2014 to 2016. SSIs were identified from National Health Safety Network (NHSN) reporting. We trained and validated 3 SSI prediction models, using (1) current CMS model variables, including hospital-specific random effects (HCA-adapted CMS model); (2) demographics and claims-based comorbidities (expanded-claims model); and (3) demographics, claims-based comorbidities, and NHSN variables (claims-plus–electronic health record [EHR] model). Discrimination, calibration, and resulting rankings were compared among all models and the current CMS model with published coefficient values. Results We identified 39 468 colon surgeries in 149 hospitals, resulting in 1216 (3.1%) SSIs. Compared to the HCA-adapted CMS model, the expanded-claims model had similar performance (c-statistic, 0.65 vs 0.67, respectively), while the claims-plus-EHR model was more accurate (c-statistic, 0.70; 95% confidence interval, .67–.73; P = .004). The sampling variation, due to the low surgical volume and small number of infections, contributed 74% of the total variation in observed SSI rates between hospitals. When CMS model rankings were compared to those from the expanded-claims and claims-plus-EHR models, 18 (15%) and 26 (22%) hospitals changed quartiles, respectively, and 10 (8.3%) and 12 (10%) hospitals changed into or out of the lowest-performing quartile, respectively. Conclusions An expanded set of variables improved colon SSI risk predictions and quartile assignments, but low procedure volumes and SSI events remain a barrier to effectively comparing hospitals., Using additional variables can improve risk adjustments of hospital-level colon surgical site infection rates, but have limited impact on financial penalties. Low procedure and infection rates contribute to much of the between-hospital variation.

Purpose To assess antibiotic selection, administration, and prescribing practices in emergency departments across a large hospital system using evidence-based practices and susceptibility patterns. Methods This retrospective data review was conducted using health system–level electronic data compiled from 145 emergency departments (EDs) across the United States. Data were examined for national generalizability, most common diagnoses of infectious origin seen in nonadmitted patients in the ED, most commonly administered antibiotics in the ED, and geographically defined areas’ unique patterns of antibiotic resistance and susceptibility. Results More than 627,000 unique patient encounters and 780,000 antibiotic administrations were assessed for trends in patient demographics, antibiotics administered for a diagnosis of infectious origin, and corresponding susceptibility patterns. Results indicated that practices in the EDs of this health system aligned with evidence-based practices for streptococcal pharyngitis, otitis media, cellulitis, and uncomplicated urinary tract infections. Conclusion These results provide a representative sample of the current state of practices within many EDs across the United States for nonadmitted patients. A similar data reconstruction can be completed by other health systems to assess their prescribing practices in the ED to improve and elevate care for patients visiting the emergency room and treated as outpatients.

Background The profound changes wrought by coronavirus disease 2019 (COVID-19) on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). We aimed to evaluate the association between COVID-19 surges and HAI and cluster rates. Methods In 148 HCA Healthcare-affiliated hospitals, from 1 March 2020 to 30 September 2020, and a subset of hospitals with microbiology and cluster data through 31 December 2020, we evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month. Results Central line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased. There were 60% (95% confidence interval [CI]: 23–108%) more CLABSI, 43% (95% CI: 8–90%) more CAUTI, and 44% (95% CI: 10–88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus, and Gram-negative organisms, were each significantly associated with COVID-19 surges. Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased. Conclusions COVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention.

OBJECTIVES Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis. DESIGN Retrospective cohort study. SETTING About 373 U.S. hospitals. PATIENTS Adults hospitalized between January 2009 and September 2015. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness.The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60-0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7-123.5%). CONCLUSIONS Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers.

Background The profound changes wrought by COVID-19 on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). Objective Evaluate the association between COVID-19 surges and HAI or cluster rates Methods Design: Prospective cohort study Setting 148 HCA Healthcare-affiliated hospitals, 3/1/2020-9/30/2020, and a subset of hospitals with microbiology and cluster data through 12/31/2020 Patients All inpatients Measurements We evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month at each hospital. Results Central line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased (P ≤ 0.001 for all), with 60% (95% CI, 23 to 108%) more CLABSI, 43% (95% CI, 8 to 90%) more CAUTI, and 44% (95% CI, 10 to 88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection (CDI) was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus and Gram-negative organisms were each significantly associated with COVID-19 surges (P < 0.05 for all). Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased (P = 0.02). Limitations Variations in surveillance and reporting may affect HAI data. Table 1. Effect of an increase in number of COVID-19 discharges on HAIs and hospital-onset pathogens Figure 1. Predicted mean HAI rates as COVID-19 discharges increase Predicted mean HAI rate by increasing monthly COVID-19 discharges. Panel a. CLABSI, Panel b, CAUTI Panel c. MRSA Bacteremia, Panel d. CDI. Data are stratified by small, medium and large hospitals. Figure 2. Monthly comparison of COVID discharges to clusters COVID-19 discharges and the number of clusters of hospital-onset pathogens are correlated throughout the pandemic. Conclusion COVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention. Disclosures Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Eunice J. Blanchard, MSN RN, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Micaela H. Coady, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Deborah S. Yokoe, MD, MPH, Nothing to disclose Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)

Background Up to 40% of hospitalized patients receive unnecessary or inappropriately broad antibiotics despite a low risk of multidrug-resistant organism (MDRO) infection. Empiric standard spectrum antibiotic use would reduce extended-spectrum (ES) antibiotic exposure and future resistance. We evaluated whether computerized prescriber order entry prompts providing patient-specific MDRO risk estimates could reduce ES antibiotic use compared to routine stewardship practices in patients hospitalized with urinary tract infection (UTI). Methods This 59-hospital cluster randomized trial compared: 1) INSPIRE prompts providing patient-specific MDRO UTI risk estimates at order entry and recommended standard spectrum antibiotics for risk < 10% versus 2) routine stewardship practices. Prompt used an absolute MDRO risk algorithm based on a 140 hospital data set. Trial population included adults treated with antibiotics for UTI in ED or non-ICU wards in first 3 days of admission (empiric days); prompt was triggered if ES antibiotics were ordered. Prescribers received feedback on prompt response. Trial periods: 18-month Baseline (Apr 2017–Sept 2018); 6-month Phase-in (Oct 2018–Mar 2019); 15-month Intervention (Apr 2019 – June 2020). Primary outcome was ES antibiotic days of therapy (ES-DOT) per empiric day; secondary outcomes were a) vancomycin and b) anti-pseudomonal DOT per empiric day. Unadjusted, as-randomized analyses used generalized linear mixed effects models to assess differences in ES-DOT rates between the intervention vs baseline period across arms (difference in differences), while clustering by patient and hospital. Results Results: We randomized 59 hospitals in 12 states, with 87,749 and 66,996 non-ICU UTI admissions in baseline and intervention periods, respectively. Intervention group had a a 21% reduction in ES-DOT compared to routine care. Vancomycin and anti-pseudomonal DOT were similarly reduced in the intervention group by 17% and 23%, respectively (Table). Conclusion Conclusion: INSPIRE order entry prompts providing real-time, patient-specific MDRO risk estimates with recommendation to use standard spectrum antibiotics in low risk patients significantly reduced empiric ES prescribing in adults admitted with UTI. Disclosures Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Syma Rashid, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Taliser R. Avery, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kimberly N. Smith, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Brandon Carver, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Caren Spencer-Smith, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jason Hickok, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Arjun Srinivasan, MD, Nothing to disclose John A. Jernigan, MD, MS, Nothing to disclose Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

Background Up to 40% of hospitalized patients receive unnecessary or inappropriately broad antibiotics despite a low risk of multidrug-resistant organism (MDRO) infection. Empiric standard spectrum antibiotic use would reduce extended-spectrum (ES) antibiotic exposure and future resistance. We evaluated whether computerized prescriber order entry prompts providing patient-specific MDRO risk estimates could reduce ES antibiotic use compared to routine stewardship practices in patients hospitalized with pneumonia. Methods This 59 hospital cluster-randomized trial compared: 1) INSPIRE prompts providing patient-specific MDRO pneumonia risk estimates at order entry and recommended standard spectrum antibiotics for risk < 10% versus 2) routine stewardship practices. Prompt used an absolute MDRO risk algorithm based on a 140 hospital data set. Trial population included adults treated with antibiotics for pneumonia in ED or non-ICU wards in first 3 days of admission (empiric days); prompt was triggered if ES antibiotics were ordered. Prescribers received feedback on prompt response. Trial periods: 18-month Baseline (Apr 2017–Sept 2018); 6-month Phase-in (Oct 2018–Mar 2019); 15-month Intervention (Apr 2019 – June 2020). Primary outcome was ES antibiotic days of therapy (ES-DOT) per empiric day; secondary outcomes were a) vancomycin and b) anti-pseudomonal DOT per empiric day. Unadjusted, as-randomized analyses used generalized linear mixed effects models to assess differences in ES-DOT rates between the intervention vs baseline period across arms (difference in differences), while clustering by patient and hospital. Results We randomized 59 hospitals in 12 states, with 59,897 and 51,486 non-ICU pneumonia admissions in baseline and intervention periods, respectively. Intervention group had a 33% reduction in ES-DOT compared to routine care. Vancomycin and anti-pseudomonal DOT were similarly reduced in the intervention group by 27% and 33%, respectively (Table). Conclusion INSPIRE order entry prompts providing real-time, patient-specific MDRO risk estimates with recommendation to use standard spectrum antibiotics in low risk patients significantly reduced empiric ES prescribing in adults admitted with pneumonia. Disclosures Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Syma Rashid, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Taliser R. Avery, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Micaela H. Coady, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kimberly N. Smith, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Brandon Carver, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Caren Spencer-Smith, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jason Hickok, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Arjun Srinivasan, MD, Nothing to disclose John A. Jernigan, MD, MS, Nothing to disclose Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

Background ICU universal decolonization with daily chlorhexidine (CHG) baths plus mupirocin nasal decolonization reduces all-cause bloodstream infections (BSI) and MRSA clinical cultures. We assessed nasal iodophor, an antiseptic less susceptible to resistance, in place of mupirocin. Methods We conducted a cluster randomized non-inferiority trial in ICUs, comparing universal decolonization with: 1) Mupirocin-CHG: daily CHG baths and 5 days of twice daily nasal mupirocin, to 2) Iodophor-CHG: same regimen, substituting twice daily 10% povidone-iodine for mupirocin. All adult ICUs in a hospital were assigned to the same strategy. We compared each hospital’s outcomes during the 18-month intervention (Nov 2017-Apr 2019) to its own baseline (May 2015-Apr 2017), during which all hospitals used mupirocin-CHG. The primary outcome was ICU-attributable S. aureus clinical isolates. Secondary outcomes included ICU-attributable MRSA clinical isolates and all-cause BSI. As randomized and as treated analyses used unadjusted proportional hazards models assessing differences in outcomes between baseline and intervention periods across the two groups, accounting for clustering by hospital and patient. Results We randomized 137 hospitals with 233 ICUs in 18 states. There were 442,544 admissions in the baseline period and 349,262 in the intervention period. Median ICU length of stay was 4 days. ICU types included mixed medical surgical (56%), medical (9%), surgical (11%), cardiac (15%), and neurologic (9%). CHG adherence was similar in both arms (85%), but adherence was greater for mupirocin (90%) than iodophor (82%). Primary as-randomized results (Table, Figure) exceeded the non-inferiority margin in favor of mupirocin, for S. aureus clinical cultures (21% superiority, P< 0.001) and for MRSA clinical cultures (20% superiority, P< 0.001). The regimens had similar BSI hazards. Analyses of fully adherent patients are in progress. Figure - Primary and Secondary Outcomes of Mupirocin Iodophor Swap Out Trial Conclusion Universal iodophor-CHG was equivalent to mupirocin-CHG for ICU BSI prevention. Mupirocin-CHG was superior to iodophor-CHG for S. aureus and MRSA clinical isolates, potentially due to greater adherence to mupirocin. Disclosures Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Taliser R. Avery, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Syma Rashid, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Katherine Haffenreffer, BS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Lauren Shimelman, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Caren Spencer-Smith, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Selsebil Sljivo, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Ed Rosen, BS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Micaela H. Coady, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Eunice J. Blanchard, MSN RN, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kimberly Reddish, DNP, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Brandon Carver, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kimberly N. Smith, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jason Hickok, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Karen Lolans, BS, Medline (Research Grant or Support) Nadia Khan, BS, Medline (Research Grant or Support) John A. Jernigan, MD, MS, Nothing to disclose Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)

Background A reliable risk-adjusted sepsis outcome measure could complement current national process metrics by identifying outlier hospitals and catalyzing additional improvements in care. However, it is unclear whether integrating clinical data into risk adjustment models identifies similar high- and low-performing hospitals compared with administrative data alone, which are simpler to acquire and analyze. Methods We ranked 200 US hospitals by their Centers for Disease Control and Prevention Adult Sepsis Event (ASE) mortality rates and assessed how rankings changed after applying (1) an administrative risk adjustment model incorporating demographics, comorbidities, and codes for severe illness and (2) an integrated clinical and administrative model replacing severity-of-illness codes with laboratory results, vasopressors, and mechanical ventilation. We assessed agreement between hospitals’ risk-adjusted ASE mortality rates when ranked into quartiles using weighted kappa statistics (к). Results The cohort included 4 009 631 hospitalizations, of which 245 808 met ASE criteria. Risk-adjustment had a large effect on rankings: 22/50 hospitals (44%) in the worst quartile using crude mortality rates shifted into better quartiles after administrative risk adjustment, and a further 21/50 (42%) of hospitals in the worst quartile using administrative risk adjustment shifted to better quartiles after incorporating clinical data. Conversely, 14/50 (28%) hospitals in the best quartile using administrative risk adjustment shifted to worse quartiles with clinical data. Overall agreement between hospital quartile rankings when risk-adjusted using administrative vs clinical data was moderate (к = 0.55). Conclusions Incorporating clinical data into risk adjustment substantially changes rankings of hospitals’ sepsis mortality rates compared with using administrative data alone. Comprehensive risk adjustment using both administrative and clinical data is necessary before comparing hospitals by sepsis mortality rates.

Supplemental Digital Content is available in the text., Objectives: Variability in hospital-level sepsis mortality rates may be due to differences in case mix, quality of care, or diagnosis and coding practices. Centers for Disease Control and Prevention’s Adult Sepsis Event definition could facilitate objective comparisons of sepsis mortality rates between hospitals but requires rigorous risk-adjustment tools. We developed risk-adjustment models for Adult Sepsis Events using administrative and electronic health record data. Design: Retrospective cohort study. Setting: One hundred thirty-six U.S. hospitals in Cerner HealthFacts (derivation dataset) and 137 HCA Healthcare hospitals (validation dataset). Patients: A total of 95,154 hospitalized adult patients (derivation) and 201,997 patients (validation) meeting Centers for Disease Control and Prevention Adult Sepsis Event criteria. Interventions: None. Measurements and Main Results: We created logistic regression models of increasing complexity using administrative and electronic health record data to predict in-hospital mortality. An administrative model using demographics, comorbidities, and coded markers of severity of illness at admission achieved an area under the receiver operating curve of 0.776 (95% CI, 0.770–0.783) in the Cerner cohort, with diminishing calibration at higher baseline risk deciles. An electronic health record–based model that integrated administrative data with laboratory results, vasopressors, and mechanical ventilation achieved an area under the receiver operating curve of 0.826 (95% CI, 0.820–0.831) in the derivation cohort and 0.827 (95% CI, 0.824–0.829) in the validation cohort, with better calibration than the administrative model. Adding vital signs and Glasgow Coma Score minimally improved performance. Conclusions: Models incorporating electronic health record data accurately predict hospital mortality for patients with Adult Sepsis Events and outperform models using administrative data alone. Utilizing laboratory test results, vasopressors, and mechanical ventilation without vital signs may achieve a good balance between data collection needs and model performance, but electronic health record–based models must be attentive to potential variability in data quality and availability. With ongoing testing and refinement of these risk-adjustment models, Adult Sepsis Event surveillance may enable more meaningful comparisons of hospital sepsis outcomes and provide an important window into quality of care.

Antimicrobial resistance (AR) is one of the most serious public health threats today, which has been accelerated by the overuse and misuse of antimicrobials in humans and animals plus inadequate infection prevention. Numerous studies have shown a relationship between antimicrobial use and resistance. Antimicrobial stewardship (AS) programs have been shown to improve patient outcomes, reduce antimicrobial adverse events, and decrease AR. AS programs, when implemented alongside infection control measures, especially hand-hygiene interventions, were more effective than implementation of AS alone. Targeted coordination and prevention strategies are critical to stopping the spread of multidrug-resistant organisms.

© 2017 The Author(s). Background: The clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped. Methods: To strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design. Results: In this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs. Conclusion: A planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity.

While conducting a set of large-scale multi-site pragmatic clinical trials involving high-impact public health issues such as end-stage renal disease, opioid use, and colorectal cancer, there were substantial changes to both policies and guidelines relevant to the trials. These external changes gave rise to unexpected challenges for the trials, including decisions regarding how to respond to new clinical practice guidelines, increased difficulty in implementing trial interventions, achieving separation between treatment groups, and differential responses across sites. In this article, we describe these challenges and the approaches used to address them. When deliberating appropriate action in the face of external changes during a pragmatic clinical trial, we recommend considering the well-being of the participants, clinical equipoise, and the strength and quality of the evidence associated with the change; involving those charged with data and safety monitoring; and where possible, planning for potential external changes as the trial is being designed. Any solution must balance the primary obligation to protect the well-being of participants with the secondary obligation to protect the integrity of the trial in order to gain meaningful answers to important public health questions.

Background Surgical site infection (SSI) is one of the most common health care–associated infections. Staphylococcus aureus remains the most common etiologic agent causing SSIs. Studies confirm S aureus carriage increases the risk of S aureus SSIs. The purpose of this article is to review the strategies to reduce SSIs due to S aureus focusing on nasal decolonization. Results Published studies indicate screening patients for S aureus nasal carriage and decolonizing carriers during the preoperative period decreases the risk of S aureus SSIs in cardiac and orthopedic surgery. Mupirocin remains the best topical agent at eradicating nasal S aureus however, concerns over resistance have led to development of alternative agents. Nasal povidone-iodine, alcohol-based nasal antiseptic, and photodynamic therapy are promising new interventions, but more studies are needed. Conclusions Short term nasal mupirocin is still the most studied and effective topical agent in eradicating S aureus nasal colonization. However, increasing mupirocin resistance remains an ongoing concern and newer agents are needed. Currently, preoperative S aureus decolonization often uses combination chlorhexidine gluconate bathing and nasal mupirocin considering that colonization of multiple body sites is commonly seen.

BACKGROUND: The Antimicrobial Use (AU) Option of the Centers for Disease Control and Prevention’s National Healthcare Safety Network (NHSN) is a surveillance resource that can provide actionable data for antibiotic stewardship programs. Such data are used to enable measurements of AU across hospitals and before, during, and after stewardship interventions. METHODS: We used monthly AU data and annual facility survey data submitted to the NHSN to describe hospitals and neonatal patient care locations reporting to the AU Option in 2017, examine frequencies of most commonly reported agents, and analyze variability in AU rates across hospitals and levels of care. We used results from these analyses in a collaborative project with Vermont Oxford Network to develop neonatal-specific Standardized Antimicrobial Administration Ratio (SAAR) agent categories and neonatal-specific NHSN Annual Hospital Survey questions. RESULTS: As of April 1, 2018, 351 US hospitals had submitted data to the AU Option from at least 1 neonatal unit. In 2017, ampicillin and gentamicin were the most frequently reported antimicrobial agents. On average, total rates of AU were highest in level III NICUs, followed by special care nurseries, level II-III NICUs, and well newborn nurseries. Seven antimicrobial categories for neonatal SAARs were created, and 6 annual hospital survey questions were developed. CONCLUSIONS: A small but growing percentage of US hospitals have submitted AU data from neonatal patient care locations to NHSN, enabling the use of AU data aggregated by NHSN as benchmarks for neonatal antimicrobial stewardship programs and further development of the SAAR summary measure for neonatal AU.

OBJECTIVES: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk-adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health record (EHRs) and its impact on outcome comparisons. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was defined using EHR-derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to ≥2.0 mg/dL, decrease in platelets to

BACKGROUND:Universal skin and nasal decolonisation reduces multidrug-resistant pathogens and bloodstream infections in intensive care units. The effect of universal decolonisation on pathogens and infections in non-critical-care units is unknown. The aim of the ABATE Infection trial was to evaluate the use of chlorhexidine bathing in non-critical-care units, with an intervention similar to one that was found to reduce multidrug-resistant organisms and bacteraemia in intensive care units. METHODS:The ABATE Infection (active bathing to eliminate infection) trial was a cluster-randomised trial of 53 hospitals comparing routine bathing to decolonisation with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. The trial was done in hospitals affiliated with HCA Healthcare and consisted of a 12-month baseline period from March 1, 2013, to Feb 28, 2014, a 2-month phase-in period from April 1, 2014, to May 31, 2014, and a 21-month intervention period from June 1, 2014, to Feb 29, 2016. Hospitals were randomised and their participating non-critical-care units assigned to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistant Staphylococcus aureus (MRSA) carriers. The primary outcome was MRSA or vancomycin-resistant enterococcus clinical cultures attributed to participating units, measured in the unadjusted, intention-to-treat population as the HR for the intervention period versus the baseline period in the decolonisation group versus the HR in the routine care group. Proportional hazards models assessed differences in outcome reductions across groups, accounting for clustering within hospitals. This trial is registered with ClinicalTrials.gov, number NCT02063867. FINDINGS:There were 189 081 patients in the baseline period and 339 902 patients (156 889 patients in the routine care group and 183 013 patients in the decolonisation group) in the intervention period across 194 non-critical-care units in 53 hospitals. For the primary outcome of unit-attributable MRSA-positive or VRE-positive clinical cultures (figure 2), the HR for the intervention period versus the baseline period was 0·79 (0·73-0·87) in the decolonisation group versus 0·87 (95% CI 0·79-0·95) in the routine care group. No difference was seen in the relative HRs (p=0·17). There were 25 (

Background: Despite the well-known fact that antibiotics (AB) are not effective against viruses, many patients ask for - and all too often doctors provide – AB for treating URTIs. Over-prescribing of AB is one of the key causes for the development of bacterial resistance, which the U.S. Centers for Disease Control and Prevention (CDC) calls “one of the world's most pressing public health problems”. In addition to the CDC initiated “Get Smart About Antibiotics” campaign, focused on educating doctors the public about the importance of appropriate AB use, other programs tackling this problem include the development of new treatment paradigms. Data published at the Oregon Health & Science University demonstrated that a ‘wait-and-see’ approach, without an AB prescription for the treatment of acute childhood ear infections, was as quick, safe, and effective in resolving the infections as an AB prescription (Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-See Prescription for the Treatment of Acute Otitis Media. JAMA 2006; 296:1235-1241). Objective: To try and reduce inappropriate prescribing practices, a wait and see or delayed approach requires patients to return for a prescription if their symptoms persist or worsen. The aim of this study was to determine whether treatment with Mucinex D (Reckitt Benckiser LLC, Parsippany, New Jersey) lowers the use of antibiotics in the treatment of URTIs when compared with placebo. Methods: Patients aged 18 to 75 years with symptoms of acute URTIs were randomized to 1200 mg guaifenesin/120 mg pseudoephedrine hydrochloride extended-release, bilayer tablets or matching placebo for 7 consecutive days. Eligible patients met physician’s criteria for antibiotic therapy but were considered suitable for a wait and see approach (withholding antibiotics for ≥48 hours). Patients recorded symptom ratings via an interactive voice response system. Results: One thousand one hundred eighty-nine patients enrolled; data are presented for the modified intent-to-treat population (n = 1179). At Day 8, significantly fewer patients receiving guaifenesin/pseudoephedrine versus placebo desired antibiotics (4.2% vs 8.0%). No adverse effects were reported due to patients not taking antibiotics. Significant reductions in URTI symptoms were observed for extended-release guaifenesin/pseudoephedrine versus placebo, from Day 1 throughout the study; however, the proportion of patients experiencing overall relief at the Day 4 evening assessment (primary end point) did not reach statistical significance. Treatment-related adverse events were reported in 9.8% and 4.7% of patients receiving guaifenesin/pseudoephedrine and placebo, respectively. Conclusions: The study found that a wait and see approach was associated with decreased antibiotic use. In addition, the use of a guaifenesin pseudoephedrine combination product provided an effective symptom control compared to a placebo and a well-tolerated first-line strategy for the management of URTIs. This study was not designed to assess the effects of guaifenesin or pseudoephedrine individually. Other limitations include the need for better clinical methods to assess the effectiveness of treatments for acute symptoms of patients with URTIs. ClinicalTrials.gov identifier: NCT01202279.

© 2015 Elsevier Inc. Pragmatic clinical trials are increasingly common because they have the potential to yield findings that are directly translatable to real-world healthcare settings. Pragmatic clinical trials need to integrate research into clinical workflow without placing an undue burden on the delivery system. This requires a research partnership between investigators and healthcare system representatives. This paper, organized as a series of case studies drawn from our experience in the NIH Health Care Systems Research Collaboratory, presents guidance from informational interviews of physician–scientists, health services researchers, and delivery system leaders who recently launched pragmatic clinical trials.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

SUMMARY Colonization with health care-associated pathogens such as Staphylococcus aureus , enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida . Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections.

Background Universal decolonization with daily chlorhexidine (CHG) bathing with and without nasal decolonization has significantly reduced positive MRSA clinical cultures and bloodstream infections in adult ICUs in several clinical trials. We evaluated whether decolonization was similarly effective in a lower risk hospitalized population. Methods We conducted a 2 arm cluster-randomized trial involving a 1-year baseline period (April 2013–March 2014) and a 21-month intervention period (June 2014–February 2016). All noncritical care units in a hospital were assigned to the same strategy. These were (1) Routine Care: routine bathing product and frequency and (2) Decolonization: CHG for routine daily bathing (2% leave-on CHG) or showering (4% rinse-off CHG) for all patients plus mupirocin for 5 days for known MRSA. Universal ICU decolonization was in place in both arms by September 2013. Differences between the arms in the outcome rates between the baseline and intervention periods were assessed with proportional hazards models, using shared frailties to account for clustering by hospital. The primary analysis was as-randomized and unadjusted. Primary outcome was any MRSA or VRE clinical isolate attributable to the unit. Secondary outcome was all-cause bloodstream infections. Additional analyses adjusted for age, gender, race, Medicaid insurer, surgery, and comorbidities. Results We randomized 53 hospitals in 15 states. There were 194 adult units with 189,616 admissions in the baseline period and 340,350 in the intervention period. Common unit types included mixed medical surgical (30%), cardiac (20%), step-down (11%), medical (10%), surgical (10%), and oncology (4%). There were no significant differences between arms in the relative hazards for intervention vs. baseline for either outcome (Table and Figure). Adjusted analyses yielded similar results. Conclusion Universal daily CHG bathing or showering plus targeted mupirocin for MRSA+ patients in non-critical care units did not reduce the combination of positive MRSA and VRE clinical cultures or bloodstream infections due to all pathogens. Further analyses to assess for any differential effects in high-risk subpopulations will be important. Disclosures S. S. Huang, Sage Products: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Clorox: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; 3M: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; E. Septimus, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; K. Kleinman, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Moody, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Hickok, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. Heim, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; A. Gombosev, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Avery, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design K. Haffenreffer, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; L. Shimelman, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; M. K. Hayden, OpGen, Inc.: Receipt of donated laboratory services for project, Research support; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. A. Weinstein, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; OpGen Inc.: Receipt of donated laboratory services for project, Research support; C. Spencer-Smith, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. E. Kaganov, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. V. Murphy, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Forehand, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Lankiewicz, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. H. Coady, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design.; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. M. Portillo, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Patel Sarup, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Perlin, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. Platt, Clorox: Receipt of contributed product, Conducting clinical studies in which participating healthcare facilities are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product

Background: Appropriate testing of blood procalcitonin (PCT) can potentially inform antibiotic de-escalation in patients with severe infections. When used along with observed clinical improvements, PCT testing can support antimicrobial stewardship. However, this testing must be used optimally to ensure that it is actionable, cost-effective, and provides patient benefit. Although this test is widely used, little is known about the appropriateness of this testing in select populations. Methods: In this retrospective review, we evaluated PCT monitoring patterns and appropriateness of use and relationship to antibiotic days of therapy in a system of community hospitals. We evaluated the use of PCT testing in patients with known confounders, namely pregnancy, chronic kidney disease, or neutropenia, which we classified as “inappropriate use” because these conditions can affect the interpretation of PCT results. We also evaluated the relationship between PCT testing and antibiotic days of therapy for patients with sepsis, pneumonia, or lower respiratory tract infections. Results: In a 1-year period, ∼206,302 PCT tests were performed at 146 facilities, an average of ∼1,413 per facility per year. Approximately 27.7% of these tests were given to patients who were pregnant or had a confounding comorbidity such as chronic kidney disease or neutropenia. Of these “inappropriate” tests, >90% were given to patients with chronic kidney disease. Older patients (aged 60–80 years, n = 93,021) were more likely to receive a PCT test while also having a confounding comorbidities; 24% of older patients with a PCT test also had chronic kidney disease. Of all patients with a PCT test and chronic kidney disease, ∼76% were also diagnosed with either sepsis, pneumonia, or lower respiratory tract infections. Conclusions: Confounding conditions can affect PCT levels independently of infection. Additionally, some clinicians use PCT tests as probes for other physiological maladies. This analysis demonstrated that there is opportunity for education about the appropriate use of this test, how to interpret results in the presence of confounding conditions, and how to transform PCT test results into actions that facilitate antimicrobial stewardship and better patient care.Funding: NoneDisclosures: None

Rapid diagnostic testing (RDT) combined with an antimicrobial stewardship program (ASP) has shown improved outcomes in bloodstream infections (BSIs). We assessed the impact of RDT, surveillance software, and ASP pharmacist staffing on time to optimal therapy (TOT) in Gram-negative BSIs. Adults with Gram-negative BSIs were included in this retrospective evaluation across 2 study periods. The preimplementation group (n = 121) had longer TOT than the postimplementation group (n = 120) (59.6 ± 36.2 h versus 29.0 ± 24.2 h, P 0.001). Escalation (51.1 ± 26.4 h versus 16.9 ± 15.7 h, P 0.001) and de-escalation (63.1 ± 39.5 h versus 39.2 ± 25.6 h, P 0.01) of therapy were shorter in the postimplementation group. TOT for patients with multidrug-resistant organisms (MDROs) was shorter in the postimplementation group (61.8 ± 37.2 h versus 21.9 ± 18.8 h, P 0.001). TOT was shorter during fully staffed clinical pharmacist hours (30.6 ± 58.9 h versus 19.7 ± 31.7 h, p = 0.014). Implementation of RDT and surveillance software with an ASP decreased TOT for Gram-negative BSIs, including MDROs.

BACKGROUND: Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge. METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence). RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary out-comes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants. CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234.)

Background The epidemic Clostridioides difficile ribotype 027 strain resulted from the dissemination of 2 separate fluoroquinolone-resistant lineages: FQR1 and FQR2. Both lineages were reported to originate in North America; however, confirmatory large-scale investigations of C difficile ribotype 027 epidemiology using whole genome sequencing has not been undertaken in the United States. Methods Whole genome sequencing and single-nucleotide polymorphism (SNP) analysis was performed on 76 clinical ribotype 027 isolates obtained from hospitalized patients in Texas with C difficile infection and compared with 32 previously sequenced worldwide strains. Maximum-likelihood phylogeny based on a set of core genome SNPs was used to construct phylogenetic trees investigating strain macro- and microevolution. Bayesian phylogenetic and phylogeographic analyses were used to incorporate temporal and geographic variables with the SNP strain analysis. Results Whole genome sequence analysis identified 2841 SNPs including 900 nonsynonymous mutations, 1404 synonymous substitutions, and 537 intergenic changes. Phylogenetic analysis separated the strains into 2 prominent groups, which grossly differed by 28 SNPs: the FQR1 and FQR2 lineages. Five isolates were identified as pre-epidemic strains. Phylogeny demonstrated unique clustering and resistance genes in Texas strains indicating that spatiotemporal bias has defined the microevolution of ribotype 027 genetics. Conclusions Clostridioides difficile ribotype 027 lineages emerged earlier than previously reported, coinciding with increased use of fluoroquinolones. Both FQR1 and FQR2 ribotype 027 epidemic lineages are present in Texas, but they have evolved geographically to represent region-specific public health threats.

Background Antimicrobial stewardship is recommended as a crucial mechanism to reduce the emergence of antimicrobial resistance. The purpose of this article was to describe implementation of antimicrobial management programs (AMPs) across a large health system of community hospitals. Methods The initiative was structured in 4 phases. Although each phase was implemented sequentially, facilities could progress at their own pace. Phase goals needed to be met before moving to the next phase. The 4 phases included preparatory, foundational, clinical care optimization, and refinement. A survey was administered prior to the initiative in 2010, and modified surveys were administered in 2015 and 2017. Results Stewardship activities improved in most areas of the AMP initiative in 2015, with substantial improvement by 2017. Important changes included an increase in established programs, from 82% in 2010 to 88% and 96% in 2015 and 2017, respectively. Physician Champions increased from 73% in 2010 to 94% in 2017. Advances were made in the use of evidence-based treatment recommendations, antibiogram development, prospective audit and feedback for antimicrobials, tracking of antibiotic usage metrics, and a cost reduction of 40% from baseline. Conclusion A well-designed, phased approach to implementing AMP can help community hospitals and hospital systems recognize substantial clinical and financial benefits.

The classification system for categorizing the riskiness of a clinical trial is largely defined by the body of federal regulations known as the Common Rule (45 CFR 46, Subpart A) and by regulations governing the US Food and Drug Administration (FDA) codified in 21 CFR 50. This rule is applied according to the interpretation of institutional review boards (IRBs) charged with overseeing the research. If a clinical trial is determined by an IRB to constitute “minimal risk,” there are important practical implications: the IRB may allow waiver or alteration of the informed consent process; the study may be carried out in certain vulnerable populations; or the study may be reviewed by IRBs using an expedited process. However, it is unclear how the risk levels of pragmatic clinical trials (PCTs) should be assessed. Such trials typically compare existing, widely used medical therapies or interventions in the setting of routine clinical practice. Some of the therapies may be considered risky of themselves but the study comparing them may or may not add to that pre-existing level of risk. In this paper, we examine current research regulations and common interpretations of those regulations and suggest that current interpretation and application of regulations governing minimal-risk classification are marked by a high degree of variability and confusion, which in turn may ultimately harm patients by delaying or hindering potentially beneficial research. We advocate for a clear differentiation between the risks associated with a given therapy and the incremental risk incurred during research evaluating those therapies as a basic principle for evaluating the risk of a clinical study. We then examine two studies that incorporate aspects of PCTs and consider how various factors including patient perspectives, clinical equipoise, practice variation, and research methods such as cluster randomization contribute to current and evolving concepts of minimal risk, and how this understanding in turn affects the design and conduct of PCTs.

Background: Universal skin and nasal decolonization reduces multidrug-resistant pathogens and bloodstream infections in intensive care units. The effect of universal decolonization on pathogens and infections in non-critical care units is unknown. Methods: A two-arm cluster-randomized trial was conducted in 53 hospitals in the Hospital Corporation of America Healthcare system. Hospitals were randomized and their participating non-critical care units assigned to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistant Staphylococcus aureus (MRSA) carriers. The trial involved a 12-month baseline (Mar 2013-Feb 2014) and 21-month intervention (Jun 2014-Feb 2016). Primary outcome was MRSA or vancomycin-resistant enterococcus (VRE) clinical cultures attributed to participating units, and secondary outcome was all-pathogen bloodstream infection. Proportional hazards models assessed differences in outcome reductions across arms, accounting for clustering by hospital. Post-hoc subgroup analyses were performed. Findings: There were 189,081 patients in the baseline period and 339,902 patients in the intervention period across 194 non-critical care units in 53 hospitals. Hazard ratios for MRSA/VRE clinical isolates during intervention vs. baseline periods were 0·87 (CI:0·79, 0·95) for routine care, and 0·79 (CI:0·73, 0·87) for decolonization (p=0·17), and 0·96 (CI:0·85, 1·08) and 0·90 (0·81, 1·01) for all-pathogen bloodstream infection, respectively (p=0·44). Among patients with central venous catheters, midline catheters, or lumbar drains, the hazard ratio for MRSA/VRE clinical cultures was 1·17 (CI:1·00, 1·37) for routine care and 0·80 (CI:0·69, 0·92) for decolonization, (p=0·0004), and the hazard ratio for all-pathogen bloodstream infections was 1·13 (CI:0·96, 1·33) for routine care and 0·82 (CI:0·71, 0·94) for decolonization, p=0·004. Interpretation: Decolonization with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not reduce multidrug-resistant organisms or all-pathogen bloodstream infection in all non-critical care patients, but patients with invasive devices experienced 37% reduction in MRSA/VRE and 31% reduction in bloodstream infections. Clinical Trial Registration Number: clinicaltrials.gov Identifier: NCT0206386 Funding Statement: This project was funded by the National Institutes of Health Common Fund and administered by the National Institute of Allergy and Infectious Diseases (UH2/UH3 AT007769‐01 (Huang)). Declaration of Interest: Sage Products and Molnlycke contributed antiseptic chlorhexidine product to this trial. Investigators are also conducting other studies in which contributed antiseptic product is provided to participating hospitals and nursing homes from Stryker (Sage Products) (KK, LH, MHC, MKH, RAW, SSH), 3M (LH, SSH), Clorox (CS, ES, JH, JM, JP, KH, KK, LH, LS, MHC, MKH, RAW, RP, SSH, TRA), Xttrium (LH, SSH), and Medline (CS, ES, JH, JM, JP, KH, KK, LH, LS, MHC, MKH, RAW, RP, SSH, TRA). Investigator-initiated grant funds were received from Clorox (MKH, MHC, LS, KH, RP). Companies contributing product or providing grant funds have no role in the design, conduct, analysis, or publication of the ABATE Infection Trial or other studies conducted by these investigators. All other authors have no disclosures. Ethics Approval Statement: Central IRB approval was obtained from Harvard Pilgrim Health Care with a waiver of informed consent. All participating hospitals formally ceded IRB oversight to the HPHC IRB, except for the designated medical center IRB (Chippenham & Johnston Willis Hospitals) that provided prisoner oversight for the trial.