A Trial of Automated Outbreak Detection to Reduce Hospital Pathogen Spread.

BACKGROUND: Detection 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. METHODS: We 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. RESULTS: Real-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). CONCLUSIONS: Automated 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.).

Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial.

Importance: Pneumonia 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. Objective: To 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 Participants: Cluster-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. Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies. Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups. Conclusions and Relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged. Trial Registration: ClinicalTrials.gov Identifier: NCT03697070.

Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.

Importance: Urinary 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. Objective: To 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 Participants: Cluster-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). Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods. Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively. Conclusions and Relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers. Trial Registration: ClinicalTrials.gov Identifier: NCT03697096.

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial.

Importance: Universal 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. Objective: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. Design, Setting, and Participants: Two-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. Intervention: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). Main Outcomes and Measures: ICU-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%. Results: Among 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 < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). Conclusions and Relevance: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. Trial Registration: ClinicalTrials.gov Identifier: NCT03140423.

Discontinuation of atorvastatin use in hospital is associated with increased risk of mortality in COVID-19 patients.

BACKGROUND: Statins are a commonly used class of drugs, and reports have suggested that their use may affect COVID-19 disease severity and mortality risk. OBJECTIVE: The purpose of this analysis was to determine the effect of discontinuation of previous atorvastatin therapy in patients hospitalized for COVID-19 on the risk of mortality and ventilation. METHODS: Data from 146,413 hospitalized COVID-19 patients were classified according to statin therapy. Home + in hospital atorvastatin use (continuation of therapy); home + no in hospital atorvastatin use (discontinuation of therapy); no home + no in hospital atorvastatin use (no statins). Logistic regression was performed to assess the association between atorvastatin administration and either mortality or use of mechanical ventilation during the encounter. RESULTS: Continuous use of atorvastatin (home and in hospital) was associated with a 35% reduction in the odds of mortality compared to patients who received atorvastatin at home but not in hospital (odds ratio [OR]: 0.65, 95% confidence interval [CI]: 0.59-0.72, p < .001). Similarly, the odds of ventilation were lower with continuous atorvastatin therapy (OR: 0.70, 95% CI: 0.64-0.77, p < .001). CONCLUSIONS: Discontinuation of previous atorvastatin therapy is associated with worse outcomes for COVID-19 patients. Providers should consider maintaining existing statin therapy for patients with known or suspected previous use.

Prevalence and Outcomes of Previously Healthy Adults Among Patients Hospitalized With Community-Onset Sepsis.

BACKGROUND: Devastating cases of sepsis in previously healthy patients have received widespread attention and have helped to catalyze state and national mandates to improve sepsis detection and care. However, it is unclear what proportion of patients hospitalized with sepsis previously were healthy and how their outcomes compare with those of patients with comorbidities. RESEARCH QUESTION: Among adults hospitalized with community-onset sepsis, how many previously were healthy and how do their outcomes compare with those of patients with comorbidities? STUDY DESIGN AND METHODS: We retrospectively identified all adults with community-onset sepsis hospitalized in 373 US hospitals from 2009 through 2015 using clinical indicators of presumed infection and organ dysfunction (Centers for Disease Control and Prevention's Adult Sepsis Event criteria). Comorbidities were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. We applied generalized linear mixed models to measure the associations between the presence or absence of comorbidities and short-term mortality (in-hospital death or discharge to hospice), adjusting for severity of illness on admission. RESULTS: Of 6,715,286 hospitalized patients, 337,983 (5.0%) were hospitalized with community-onset sepsis. Most patients with sepsis (329,052 [97.4%]) had received a diagnosis of at least one comorbidity; only 2.6% previously were healthy. Patients with sepsis who previously were healthy were younger than those with comorbidities (mean age, 58.0 ± 19.8 years vs 67.0 ± 16.5 years), were less likely to require ICU care on admission (37.9% vs 50.5%), and were more likely to be discharged home (57.9% vs 45.6%), rather than to subacute facilities (16.3% vs 30.8%), but showed higher short-term mortality rates (22.8% vs 20.8%; P < .001 for all). The association between previously healthy status and higher short-term mortality persisted after risk adjustment (adjusted OR, 1.99; 95% CI, 1.87-2.13). INTERPRETATION: The vast majority of patients hospitalized with community-onset sepsis harbor pre-existing comorbidities. However, previously healthy patients may be more likely to die when they seek treatment at the hospital with sepsis compared with patients with comorbidities. These findings underscore the importance of early sepsis recognition and treatment for all patients.

The Impact of Coronavirus Disease 2019 (COVID-19) on Healthcare-Associated Infections.

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.

Hyperglycaemia increases mortality risk in non-diabetic patients with COVID-19 even more than in diabetic patients.

AIM: Diabetes has been identified as a risk factor for poor outcomes in patients with COVID-19. We examined the association of hyperglycaemia, both in the presence and absence of pre-existing diabetes, with severity and outcomes in COVID-19 patients. METHODS: Data from 74,148 COVID-19-positive inpatients with at least one recorded glucose measurement during their inpatient episode were analysed for presence of pre-existing diabetes diagnosis and any glucose values in the hyperglycaemic range (>180 mg/dl). RESULTS: Among patients with and without a pre-existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70-180 mg/dl) in both groups (non-diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). When adjusting for patient age, BMI, severity on admission and oxygen saturation on admission, this increased risk of mortality persisted and varied by diabetes diagnosis. Among patients with a pre-existing diabetes diagnosis, any hyperglycaemic value during the episode was associated with a substantial increase in the odds of mortality (OR: 1.77, 95% CI: 1.52-2.07); among patients without a pre-existing diabetes diagnosis, this risk nearly doubled (OR: 3.07, 95% CI: 2.79-3.37). CONCLUSION: This retrospective analysis identified hyperglycaemia in COVID-19 patients as an independent risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. This indicates that the extent of glucose control could serve as a mechanism for modifying the risk of COVID-19 morality in the inpatient environment.

No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19.

BACKGROUND: The use of hydroxychloroquine (HCQ), with or without concurrent administration of azithromycin (AZM), for treatment of COVID-19 has received considerable attention. The purpose of this study was to determine whether HCQ administration is associated with improved mortality in COVID-19 patients. METHODS: We conducted a retrospective analysis of data collected during the care process for COVID-19 positive patients discharged from facilities affiliated with a large healthcare system in the United States as of April 27, 2020. Patients were categorized by treatment with HCQ (in addition to standard supportive therapy) or receipt of supportive therapy with no HCQ. Patient outcomes were evaluated for in-hospital mortality. Patient demographics and clinical characteristics were accounted for through a multivariable regression analysis. RESULTS: A total of 1669 patients were evaluated (no HCQ, n = 696; HCQ, n = 973). When adjusting for patient characteristics, receipt of AZM, and severity of disease at admission, there was no beneficial effect of receipt of HCQ on the risk of death. In this population, there was an 81% increase in the risk of mortality among patients who received HCQ at any time during their hospital stay versus no HCQ exposure (OR: 1.81, 95% CI: 1.20-2.77, p = 0.01). CONCLUSIONS: In this retrospective analysis, we found that there was no benefit of administration of HCQ on mortality in COVID-19 patients. These results support recent changes to clinical trials that discourage the use of HCQ in COVID-19 patients.

Patient characteristics and admitting vital signs associated with coronavirus disease 2019 (COVID-19)-related mortality among patients admitted with noncritical illness.

OBJECTIVE: To determine risk factors for mortality among COVID-19 patients admitted to a system of community hospitals in the United States. DESIGN: Retrospective analysis of patient data collected from the routine care of COVID-19 patients. SETTING: System of >180 acute-care facilities in the United States. PARTICIPANTS: All admitted patients with positive identification of COVID-19 and a documented discharge as of May 12, 2020. METHODS: Determination of demographic characteristics, vital signs at admission, patient comorbidities and recorded discharge disposition in this population to construct a logistic regression estimating the odds of mortality, particular for those patients characterized as not being critically ill at admission. RESULTS: In total, 6,180 COVID-19+ patients were identified as of May 12, 2020. Most COVID-19+ patients (4,808, 77.8%) were admitted directly to a medical-surgical unit with no documented critical care or mechanical ventilation within 8 hours of admission. After adjusting for demographic characteristics, comorbidities, and vital signs at admission in this subgroup, the largest driver of the odds of mortality was patient age (OR, 1.07; 95% CI, 1.06-1.08; P < .001). Decreased oxygen saturation at admission was associated with increased odds of mortality (OR, 1.09; 95% CI, 1.06-1.12; P < .001) as was diabetes (OR, 1.57; 95% CI, 1.21-2.03; P < .001). CONCLUSIONS: The identification of factors observable at admission that are associated with mortality in COVID-19 patients who are initially admitted to non-critical care units may help care providers, hospital epidemiologists, and hospital safety experts better plan for the care of these patients.

Changes in hospitalized coronavirus disease 2019 (COVID-19) patient characteristics and resource use in a system of community hospitals in the United States.

Coronavirus disease 2019 (COVID-19) has migrated to regions that were initially spared, and it is likely that different populations are currently at risk for illness. Herein, we present our observations of the change in characteristics and resource use of COVID-19 patients over time in a national system of community hospitals to help inform those managing surge planning, operational management, and future policy decisions.

2019 John M. Eisenberg Patient Safety and Quality Awards: SPOTting Sepsis to Save Lives: A Nationwide Computer Algorithm for Early Detection of Sepsis: Innovation in Patient Safety and Quality at the National Level (Eisenberg Award).

BACKGROUND: In recognition of the potential of data to drive care and the need for early identification of patients with sepsis, HCA Healthcare developed an automated sepsis detection algorithm-SPOT (Sepsis Prediction and Optimization of Therapy). The algorithm was deployed at scale and served as a mechanism to reduce the time to detection and improve sepsis mortality in 173 hospitals across the United States. METHODS: The SPOT algorithm was designed as a rules-based detection of defined criteria that would interpret available electronic and basic laboratory data in near real time. Working from an organizational recognition of the need to construct a national clinical data warehouse to allow for the aggregation and analysis of data streams, HCA Healthcare designed and deployed SPOT and delivered the alert from the algorithm to the bedside to initiate existing clinical workflows for patients with sepsis. RESULTS: SPOT improved the timeliness of sepsis detection by providing alerts when signals of sepsis become available, triggering initiation of sepsis screens. This gave an advantage of about six hours over the legacy practice of sepsis screening at shift change. When deployed alongside existing sepsis improvement initiatives, SPOT was associated with an acceleration of improvement in mortality-particularly in the not-present-on-admission (NPOA) septic shock population, the patients at greatest risk for mortality. This population had seen little improvement with prior initiatives, but mortality improved 3.9 percentage points from 2018 to 2019. When accounting for seasonal variation, there was a decline in mortality rate following the deployment of SPOT, as compared to the year prior, of 9.9% for NPOA severe sepsis and 5.1% for NPOA septic shock. CONCLUSION: Development of the SPOT algorithm for the detection of sepsis from data available in the electronic health record resulted in more timely recognition, faster initiation of treatment, and improved survival for patients.

Chlorhexidine versus routine bathing to prevent multidrug-resistant organisms and all-cause bloodstream infections in general medical and surgical units (ABATE Infection trial): a cluster-randomised trial.

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 (<1%) adverse events, all involving chlorhexidine, among 183 013 patients in units assigned to chlorhexidine, and none were reported for mupirocin. INTERPRETATION: Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not significantly reduce multidrug-resistant organisms in non-critical-care patients. FUNDING: National Institutes of Health.

Advancing the Science of Healthcare Service Delivery: The NHLBI Corporate Healthcare Leaders' Panel.

There is a growing gap between available science and evidence and the ability of service providers to deliver high-quality care in a cost-effective way to the entire population. We believe that the chasm between knowledge and action is due to a lack of concerted effort among all organizations that deliver health care services across the life span of patients. Broad participation is needed and necessitates a far more explicit and concerted public-private partnership focused on large-scale transformation. In this context, the National Heart, Lung, and Blood Institute convened a panel made up of leaders of corporate health care entities, including academic health centers, and government agency representatives to inform contemporary strategic partnerships with health care companies. This article provides insights from the meeting on how to execute a transformative innovation research agenda that will foster improvements in health care service delivery by leveraging the translation of biomedical research evidence in real-world settings.

A Comprehensive Program to Reduce Rates of Hospital-Acquired Pressure Ulcers in a System of Community Hospitals.

OBJECTIVES: The prevention of hospital-acquired pressure ulcers (PrUs) has significant consequences for patient outcomes and the cost of care. Providers are challenged with evaluating available evidence and best practices, then implementing programs and motivating change in various facility environments. METHODS: In a large system of community hospitals, the Reducing Hospital Acquired-PrUs Program was developed to provide a toolkit of best practices, timely and appropriate data for focusing efforts, and continuous implementation support. Baseline data on PrU rates helped focus efforts on the most vulnerable patients and care situations. Facilities were empowered to use and adapt available resources to meet local needs and to share best practices for implementation across the system. Outcomes were measured by the rate of hospital-acquired PrUs, as gathered from patient discharge records. RESULTS: The rate of hospital-acquired stage III and IV PrUs decreased 66.3% between 2011 and 2013. Of the 149 participating facilities, 40 (27%) had zero hospital-acquired stage III and IV PrUs and 77 (52%) had a reduction in their PrU rate. Rates of all PrUs documented as present on admission did not change during this period. A comparison of different strategies used by the most successful facilities illustrated the necessity of facility-level flexibility and recognition of local workflows and patient demographics. CONCLUSIONS: Driven by the combination of a repository of evidence-based tools and best practices, readily available data on PrU rates, and local flexibility with processes, the Reducing Hospital Acquired-PrUs Program represents the successful operationalization of improvement in a wide variety of facilities.

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial.

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.