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ImportanceUrinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed.ObjectiveTo evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI.Design, setting, and participantsCluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020).InterventionsCPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (

ImportancePneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed.ObjectiveTo evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia.Design, setting, and participantsCluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020.InterventionCPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (

BackgroundDetection and containment of hospital outbreaks currently depend on variable and personnel-intensive surveillance methods. Whether automated statistical surveillance for outbreaks of health care-associated pathogens allows earlier containment efforts that would reduce the size of outbreaks is unknown.MethodsWe conducted a cluster-randomized trial in 82 community hospitals within a larger health care system. All hospitals followed an outbreak response protocol when outbreaks were detected by their infection prevention programs. Half of the hospitals additionally used statistical surveillance of microbiology data, which alerted infection prevention programs to outbreaks. Statistical surveillance was also applied to microbiology data from control hospitals without alerting their infection prevention programs. The primary outcome was the number of additional cases occurring after outbreak detection. Analyses assessed differences between the intervention period (July 2019 to January 2022) versus baseline period (February 2017 to January 2019) between randomized groups. A post hoc analysis separately assessed pre-coronavirus disease 2019 (Covid-19) and Covid-19 pandemic intervention periods.ResultsReal-time alerts did not significantly reduce the number of additional outbreak cases (intervention period versus baseline: statistical surveillance relative rate [RR]=1.41, control RR=1.81; difference-in-differences, 0.78; 95% confidence interval [CI], 0.40 to 1.52; P=0.46). Comparing only the prepandemic intervention with baseline periods, the statistical outbreak surveillance group was associated with a 64.1% reduction in additional cases (statistical surveillance RR=0.78, control RR=2.19; difference-in-differences, 0.36; 95% CI, 0.13 to 0.99). There was no similarly observed association between the pandemic versus baseline periods (statistical surveillance RR=1.56, control RR=1.66; difference-in-differences, 0.94; 95% CI, 0.46 to 1.92).ConclusionsAutomated detection of hospital outbreaks using statistical surveillance did not reduce overall outbreak size in the context of an ongoing pandemic. (Funded by the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT04053075. Support for HCA Healthcare's participation in the study was provided in kind by HCA.).

ImportanceUniversal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.ObjectiveTo compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.Design, setting, and participantsTwo-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included.InterventionUniversal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline).Main outcomes and measuresICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%.ResultsAmong the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P

In a survey of infection prevention programs, leaders reported frequent clinical and infection prevention practice modifications to avoid coronavirus disease 2019 (COVID-19) exposure that exceeded national guidance. Future pandemic responses should emphasize balanced approaches to precautions, prioritize educational campaigns to manage safety concerns, and generate an evidence-base that can guide appropriate infection prevention practices.

The Centers for Medicare and Medicaid Services require hospitals to report on quality metrics which are used to financially penalize those that perform in the lowest quartile. Surgical site infections (SSIs) are a critical component of the quality metrics that target healthcare-associated infections. However, the accuracy of such hospital profiling is highly affected by small surgical volumes which lead to a large amount of uncertainty in estimating standardized hospital-specific infection rates. Currently, hospitals with less than one expected SSI are excluded from rankings, but the effectiveness of this exclusion criterion is unknown. Tools that can quantify the classification accuracy and can determine the minimal surgical volume required for a desired level of accuracy are lacking. We investigate the effect of surgical volume on the accuracy of identifying poorly performing hospitals based on the standardized infection ratio and develop simulation-based algorithms for quantifying the classification accuracy. We apply our proposed method to data from HCA Healthcare (2014-2016) on SSIs in colon surgery patients. We estimate that for a procedure like colon surgery with an overall SSI rate of 3%, to rank hospitals in the HCA colon SSI dataset, hospitals that perform less than 200 procedures have a greater than 10% chance of being incorrectly assigned to the worst performing quartile. Minimum surgical volumes and predicted events criteria are required to make evaluating hospitals reliable, and these criteria vary by overall prevalence and between-hospital variability.

BackgroundThe 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.MethodsIn 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.ResultsCentral 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.ConclusionsCOVID-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.

Abstract Background At the outset of the COVID-19 pandemic, healthcare workers (HCWs) raised concerns about personal risks of acquiring infection during patient care. This led to more stringent infection prevention practices than CDC guidelines during a time of uncertainty about transmission and limited U.S. testing capacity. Hospitals were challenged to protect against true COVID-19 exposure risks, while avoiding use of unproven measures that could interfere with timely, high quality care. We evaluated hospital experiences with HCW COVID-19 exposure concerns impacting clinical workflow/management. Methods We conducted a 32-question structured survey of hospital infection prevention leaders (one per hospital) from CDC Prevention Epicenters, University of California (CA) Health system, HCA Healthcare, and the Southern CA Metrics Committee between May–Dec, 2020. We assessed facility characteristics and COVID-19 exposure concerns causing changes in respiratory care, procedure delays/modifications, requests to change infection prevention processes, disruptions in routine medical care, and health impacts of PPE overuse. Percentages were calculated among respondents for each question. Results Respondents represented 53 hospitals: 22 (42%) were small (< 200 beds), 14 (26%) medium (200-400 beds), and 17 (32%) large ( >400 beds) facilities. Of these, 11 (21%) provided Level 1 trauma care, and 22 (41%) provided highly immunocompromised patient care; 75% had cared for a substantial number of COVID-19 cases before survey completion. Majority reported changes in respiratory care delivery (71%-87%), procedural delays (75%-87%), requests to change infection prevention controls/protocols (58%-96%), and occupational health impacts of PPE overuse including skin irritation (98%) and carbon dioxide narcosis symptoms (55%) (Table). Conclusion HCW concerns over work-related COVID-19 exposure contributed to practice changes, many of which are unsupported by CDC guidance and resulted in healthcare delivery delays and alterations in clinical care. Pandemic planning and response must include the ability to rapidly develop evidence to guide infection prevention practice. 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) Kenneth Sands, MD, MPH, Medline (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) 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) Deborah S. Yokoe, MD, MPH, Nothing to disclose Jonathan Grein, MD, Gilead (Other Financial or Material Support, Speakers fees) Stuart H. Cohen, MD, Seres (Research Grant or Support) 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) Russell Poland, PhD, 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) 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)

Abstract 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)

BackgroundThe profound changes wrought by 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.MethodsIn 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, 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.ResultsCentral 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% 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.ConclusionCOVID-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.

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.

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: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 (

BackgroundHospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge.MethodsWe 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).ResultsIn 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 outcomes 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.ConclusionsPostdischarge 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 .).

BackgroundThe 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.MethodsTo 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.ResultsIn 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.ConclusionA 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.

Building on the success of initiatives put forth during the COVID-19 pandemic response, US health officials are expanding wastewater surveillance programs to track other target pathogens and diseases of public health interest. The Houston Health Department in Houston, Texas, USA, conducted a hypothesis-generating study whereby infectious disease subject matter experts suggested potential targets. This study addressed 2 criteria recommended by the National Academies of Sciences, Engineering, and Medicine for selecting wastewater targets. Results can be used as a basis of a questionnaire for a future population-based study to recommend targets of highest priority to include for expanded wastewater sampling. [ABSTRACT FROM AUTHOR]

Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution.

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.

BackgroundChallenges exist in implementing evidence-based strategies, reaching high compliance, and achieving desired outcomes. The rapid adoption of a publicly available toolkit featuring routine universal decolonization of intensive care unit (ICU) patients may affect catheter-related bloodstream infections.MethodsImplementation of universal decolonization-treatment of all ICU patients with chlorhexidine bathing and nasal mupirocin-used a prerelease version of a publicly available toolkit. Implementation in 136 adult ICUs in 95 acute care hospitals across the United States was supported by planning and deployment tactics coordinated by a central infection prevention team using toolkit resources, along with coaching calls and engagement of key stakeholders. Operational and process measures derived from a common electronic health record system provided real-time feedback about performance. Healthcare-associated central line-associated bloodstream infections (CLABSIs), using National Healthcare Safety Network surveillance definitions and comparing the preimplementation period of January 2011 through December 2012 to the postimplementation period of July 2013 through February 2014, were assessed via a Poisson generalized linear mixed model regression for CLABSI events.ResultsImplementation of universal decolonization was completed within 6 months. The estimated rate of CLABSI decreased by 23.5% (95% confidence interval, 9.8%-35.1%; P = .001). There was no evidence of a trend over time in either the pre- or postimplementation period. Adjusting for seasonality and number of beds did not materially affect these results.ConclusionsDissemination of universal decolonization of ICU patients was accomplished quickly in a large community health system and was associated with declines in CLABSI consistent with published clinical trial findings.

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.

BackgroundUrinary tract infections (UTIs) are common health-care-associated infections. Bacteriuria commonly precedes UTI and is often treated with antibiotics, particularly in hospital intensive care units (ICUs). In 2013, a cluster-randomised trial (REDUCE MRSA Trial [Randomized Evaluation of Decolonization vs Universal Clearance to Eradicate MRSA]) showed that body surface decolonisation reduced all-pathogen bloodstream infections. We aim to further assess the effect of decolonisation on bacteriuria and candiduria in patients admitted to ICUs.MethodsWe did a secondary analysis of a three-group, cluster-randomised trial of 43 hospitals (clusters) with patients in 74 adult ICUs. The three groups included were either meticillin-resistant Staphylococcus aureus (MRSA) screening and isolation, targeted decolonisation (screening, isolation, and decolonisation of MRSA carriers) with chlorhexidine and mupirocin, and universal decolonisation (no screening, all patients decolonised) with chlorhexidine and mupirocin. Protocol included chlorhexidine cleansing of the perineum and proximal 6 inches (15·24 cm) of urinary catheters. ICUs within the same hospital were assigned the same strategy. Outcomes included high-level bacteriuria (≥50 000 colony forming units [CFU]/mL) with any uropathogen, high-level candiduria (≥50 000 CFU/mL), and any bacteriuria with uropathogens. Sex-specific analyses were specified a priori. Proportional hazards models assessed differences in outcome reductions across groups, comparing an 18-month intervention period to a 12-month baseline period.Findings122 646 patients (48 390 baseline, 74 256 intervention) were enrolled. Intervention versus baseline hazard ratios (HRs) for high-level bacteriuria were 1·02 (95% CI 0·88-1·18) for screening or isolation, 0·88 (0·76-1·02) for targeted decolonisation, and 0·87 (0·77-1·00) for universal decolonisation (no difference between groups, p=0·26), with no sex-specific reductions (HRs for men: 1·09 [95% CI 0·85-1·40] for screening or isolation, 1·01 [0·79-1·29] for targeted decolonisation, and 0·78 [0·63-0·98] for universal decolonisation, p=0·12; HRs for women: 0·97 [0·80-1·17] for screening and isolation, 0·83 [0·70-1·00] for targeted decolonisation, and 0·93 [0·79-1·09] for universal decolonisation, p=0·49). HRs for high-level candiduria were 1·14 (0·95-1·37) for screening and isolation, 0·99 (0·83-1·18) for targeted decolonisation, and 0·83 (0·70-0·99) for universal decolonisation (p=0·05). Differences between sexes were due to reductions in men in the universal decolonisation group (HRs: 1·21 [95% CI 0·88-1·68] for screening or isolation, 1·01 [0·73-1·39] for targeted decolonisation, and 0·63 [0·45-0·89] for universal decolonisation, p=0·02). Bacteriuria with any CFU/mL was also reduced in men in the universal decolonisation group (HRs 1·01 [0·81-1·25] for screening or isolation, 1·04 [0·83-1·30] for targeted decolonisation, and 0·74 [0·61-0·90] for universal decolonisation, p=0·04).InterpretationUniversal decolonisation of patients in the ICU with once a day chlorhexidine baths and short-course nasal mupirocin could be a potential preventive strategy in male patients because it significantly decreases candiduria and any bacteriuria, but not for women.FundingHAI Program from AHRQ, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program, CDC Prevention Epicenters Program.

BACKGROUND To design better antimicrobial stewardship programs, detailed data on the primary drivers and patterns of antibiotic use are needed. OBJECTIVE To characterize the indications for antibiotic therapy, agents used, duration, combinations, and microbiological justification in 6 acute-care US facilities with varied location, size, and type of antimicrobial stewardship programs. DESIGN, PARTICIPANTS, AND SETTING Retrospective medical chart review was performed on a random cross-sectional sample of 1,200 adult inpatients, hospitalized (>24 hrs) in 6 hospitals, and receiving at least 1 antibiotic dose on 4 index dates chosen at equal intervals through a 1-year study period (October 1, 2009-September 30, 2010). METHODS Infectious disease specialists recorded patient demographic characteristics, comorbidities, microbiological and radiological testing, and agents used, dose, duration, and indication for antibiotic prescriptions. RESULTS On the index dates 4,119 (60.5%) of 6,812 inpatients were receiving antibiotics. The random sample of 1,200 case patients was receiving 2,527 antibiotics (average: 2.1 per patient); 540 (21.4%) were prophylactic and 1,987 (78.6%) were therapeutic, of which 372 (18.7%) were pathogen-directed at start. Of the 1,615 empirical starts, 382 (23.7%) were subsequently pathogen-directed and 1,231 (76.2%) remained empirical. Use was primarily for respiratory (27.6% of prescriptions) followed by gastrointestinal (13.1%) infections. Fluoroquinolones, vancomycin, and antipseudomonal penicillins together accounted for 47.1% of therapy-days. CONCLUSIONS Use of broad-spectrum empirical therapy was prevalent in 6 US acute care facilities and in most instances was not subsequently pathogen directed. Fluoroquinolones, vancomycin, and antipseudomonal penicillins were the most frequently used antibiotics, particularly for respiratory indications. Infect. Control Hosp. Epidemiol. 2015;37(1):70-79.

BackgroundModification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy.MethodsWe did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable.FindingsAcross the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive culture (1·99, 1·20-3·29).InterpretationBroad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials.FundingUS Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security.

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

ObjectiveTo determine rates of blood culture contamination comparing 3 strategies to prevent intensive care unit (ICU) infections: screening and isolation, targeted decolonization, and universal decolonization.DesignPragmatic cluster-randomized trial.SettingForty-three hospitals with 74 ICUs; 42 of 43 were community hospitals.PatientsPatients admitted to adult ICUs from July 1, 2009, to September 30, 2011.MethodsAfter a 6-month baseline period, hospitals were randomly assigned to 1 of 3 strategies, with all participating adult ICUs in a given hospital assigned to the same strategy. Arm 1 implemented methicillin-resistant Staphylococcus aureus (MRSA) nares screening and isolation, arm 2 targeted decolonization (screening, isolation, and decolonization of MRSA carriers), and arm 3 conducted no screening but universal decolonization of all patients with mupirocin and chlorhexidine (CHG) bathing. Blood culture contamination rates in the intervention period were compared to the baseline period across all 3 arms.ResultsDuring the 6-month baseline period, 7,926 blood cultures were collected from 3,399 unique patients: 1,099 sets in arm 1, 928 in arm 2, and 1,372 in arm 3. During the 18-month intervention period, 22,761 blood cultures were collected from 9,878 unique patients: 3,055 sets in arm 1, 3,213 in arm 2, and 3,610 in arm 3. Among all individual draws, for arms 1, 2, and 3, the contamination rates were 4.1%, 3.9%, and 3.8% for the baseline period and 3.3%, 3.2%, and 2.4% for the intervention period, respectively. When we evaluated sets of blood cultures rather than individual draws, the contamination rate in arm 1 (screening and isolation) was 9.8% (N = 108 sets) in the baseline period and 7.5% (N = 228) in the intervention period. For arm 2 (targeted decolonization), the baseline rate was 8.4% (N = 78) compared to 7.5% (N = 241) in the intervention period. Arm 3 (universal decolonization) had the greatest decrease in contamination rate, with a decrease from 8.7% (N = 119) contaminated blood cultures during the baseline period to 5.1% (N = 184) during the intervention period. Logistic regression models demonstrated a significant difference across the arms when comparing the reduction in contamination between baseline and intervention periods in both unadjusted (P = .02) and adjusted (P = .02) analyses. Arm 3 resulted in the greatest reduction in blood culture contamination rates, with an unadjusted odds ratio (OR) of 0.56 (95% confidence interval [CI], 0.044-0.71) and an adjusted OR of 0.55 (95% CI, 0.43-0.71).ConclusionIn this large cluster-randomized trial, we demonstrated that universal decolonization with CHG bathing resulted in a significant reduction in blood culture contamination.

The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients. [ABSTRACT FROM AUTHOR]

BackgroundBoth targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care-associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA).MethodsWe conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital.ResultsA total of 43 hospitals (including 74 ICUs and 74,256 patients during the intervention period) underwent randomization. In the intervention period versus the baseline period, modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation (crude rate, 3.2 vs. 3.4 isolates per 1000 days), 0.75 for targeted decolonization (3.2 vs. 4.3 isolates per 1000 days), and 0.63 for universal decolonization (2.1 vs. 3.4 isolates per 1000 days) (P=0.01 for test of all groups being equal). In the intervention versus baseline periods, hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 (crude rate, 4.1 vs. 4.2 infections per 1000 days), 0.78 (3.7 vs. 4.8 infections per 1000 days), and 0.56 (3.6 vs. 6.1 infections per 1000 days), respectively (P

BackgroundA range of strategies and approaches have been developed for preventing health care-associated infections. Understanding the variation in practices among facilities is necessary to improve compliance with existing programs and aid the implementation of new interventions.MethodsIn 2009, HCA Inc administered an electronic survey to measure compliance with evidence-based infection prevention practices as well as identify variation in products or methods, such as use of special approach technology for central vascular catheters and ventilator care. Responding adult intensive care units (ICUs) were those considering participation in a clinical trial to reduce health care-associated infections.ResultsResponses from 99 ICUs in 55 hospitals indicated that many evidenced-based practices were used consistently, including methicillin-resistant Staphylococcus aureus (MRSA) screening and use of contact precautions for MRSA-positive patients. Other practices exhibited wide variability including discontinuation of precautions and use of antimicrobial technology or chlorhexidine patches for central vascular catheters. MRSA decolonization was not a predominant practice in ICUs.ConclusionIn this large, community-based health care system, there was substantial variation in the products and methods to reduce health care-associated infections. Despite system-wide emphasis on basic practices as a precursor to adding special approach technologies, this survey showed that these technologies were commonplace, including in facilities where improvement in basic practices was needed.

BackgroundThe need for evidence about the effectiveness of therapeutics and other medical practices has triggered new interest in methods for comparative effectiveness research.ObjectiveDescribe an approach to comparative effectiveness research involving cluster randomized trials in networks of hospitals, health plans, or medical practices with centralized administrative and informatics capabilities.Research designWe discuss the example of an ongoing cluster randomized trial to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection in intensive care units (ICUs). The trial randomizes 45 hospitals to: (a) screening cultures of ICU admissions, followed by Contact Precautions if MRSA-positive, (b) screening cultures of ICU admissions followed by decolonization if MRSA-positive, or (c) universal decolonization of ICU admissions without screening.SubjectsAll admissions to adult ICUs.MeasuresThe primary outcome is MRSA-positive clinical cultures occurring >or=2 days following ICU admission. Secondary outcomes include blood and urine infection caused by MRSA (and, separately, all pathogens), as well as the development of resistance to decolonizing agents.ResultsRecruitment of hospitals is complete. Data collection will end in Summer 2011.ConclusionsThis trial takes advantage of existing personnel, procedures, infrastructure, and information systems in a large integrated hospital network to conduct a low-cost evaluation of prevention strategies under usual practice conditions. This approach is applicable to many comparative effectiveness topics in both inpatient and ambulatory settings.