Search

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

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.

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.

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.

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.).

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.

Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients, leading to substantial morbidity, mortality, and excess healthcare expenditures, and persistent gaps remain between what is recommended and what is practiced.The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.

Background: The microbiologic etiologies, clinical manifestations, and antimicrobial treatment of neonatal infections differ substantially from infections in adult and pediatric patient populations. In 2019, the Centers for Disease Control and Prevention developed neonatal-specific (Standardized Antimicrobial Administration Ratios SAARs), a set of risk-adjusted antimicrobial use metrics that hospitals participating in the National Healthcare Safety Network's (NHSN's) antimicrobial use surveillance can use in their antibiotic stewardship programs (ASPs)., Methods: The Centers for Disease Control and Prevention, in collaboration with the Vermont Oxford Network, identified eligible patient care locations, defined SAAR agent categories, and implemented neonatal-specific NHSN Annual Hospital Survey questions to gather hospital-level data necessary for risk adjustment. SAAR predictive models were developed using 2018 data reported to NHSN from eligible neonatal units., Results: The 2018 baseline neonatal SAAR models were developed for 7 SAAR antimicrobial agent categories using data reported from 324 neonatal units in 304 unique hospitals. Final models were used to calculate predicted antimicrobial days, the SAAR denominator, for level II neonatal special care nurseries and level II/III, III, and IV NICUs., Conclusions: NHSN's initial set of neonatal SAARs provides a way for hospital ASPs to assess whether antimicrobial agents in their facility are used at significantly higher or lower rates compared with a national baseline or whether an individual SAAR value is above or below a specific percentile on a given SAAR distribution, which can prompt investigations into prescribing practices and inform ASP interventions., Competing Interests: CONFLICTS OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

The COVID-19 pandemic presents a serious public health challenge in all countries. However, repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on future global health are still being investigated, including the pandemic's potential effect on the emergence and spread of global antimicrobial resistance (AMR). Critically ill COVID-19 patients may develop severe complications, which may predispose patients to infection with nosocomial bacterial and/or fungal pathogens, requiring the extensive use of antibiotics. However, antibiotics may also be inappropriately used in milder cases of COVID-19 infection. Further, concerns such as increased biocide use, antimicrobial stewardship/infection control, AMR awareness, the need for diagnostics (including rapid and point-of-care diagnostics) and the usefulness of vaccination could all be components shaping the influence of the COVID-19 pandemic. In this publication, the authors present a brief overview of the COVID-19 pandemic and associated issues that could influence the pandemic's effect on global AMR., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: The Centers for Medicare and Medicaid Services (CMS) use colon surgical site infection (SSI) rates to rank hospitals and apply financial penalties. The CMS' risk-adjustment model omits potentially impactful variables that might disadvantage hospitals with complex surgical populations., Methods: We analyzed adult patients who underwent colon surgery within facilities associated with HCA Healthcare from 2014 to 2016. SSIs were identified from National Health Safety Network (NHSN) reporting. We trained and validated 3 SSI prediction models, using (1) current CMS model variables, including hospital-specific random effects (HCA-adapted CMS model); (2) demographics and claims-based comorbidities (expanded-claims model); and (3) demographics, claims-based comorbidities, and NHSN variables (claims-plus-electronic health record [EHR] model). Discrimination, calibration, and resulting rankings were compared among all models and the current CMS model with published coefficient values., Results: We identified 39 468 colon surgeries in 149 hospitals, resulting in 1216 (3.1%) SSIs. Compared to the HCA-adapted CMS model, the expanded-claims model had similar performance (c-statistic, 0.65 vs 0.67, respectively), while the claims-plus-EHR model was more accurate (c-statistic, 0.70; 95% confidence interval, .67-.73; P = .004). The sampling variation, due to the low surgical volume and small number of infections, contributed 74% of the total variation in observed SSI rates between hospitals. When CMS model rankings were compared to those from the expanded-claims and claims-plus-EHR models, 18 (15%) and 26 (22%) hospitals changed quartiles, respectively, and 10 (8.3%) and 12 (10%) hospitals changed into or out of the lowest-performing quartile, respectively., Conclusions: An expanded set of variables improved colon SSI risk predictions and quartile assignments, but low procedure volumes and SSI events remain a barrier to effectively comparing hospitals., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine ® , iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3-4 log 10 in 15-30 s  in vitro . In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection.

Rapid diagnostic testing (RDT) combined with an antimicrobial stewardship program (ASP) has shown improved outcomes in bloodstream infections (BSIs). We assessed the impact of RDT, surveillance software, and ASP pharmacist staffing on time to optimal therapy (TOT) in Gram-negative BSIs. Adults with Gram-negative BSIs were included in this retrospective evaluation across 2 study periods. The preimplementation group (n = 121) had longer TOT than the postimplementation group (n = 120) (59.6 ± 36.2 h versus 29.0 ± 24.2 h, P < 0.001). Escalation (51.1 ± 26.4 h versus 16.9 ± 15.7 h, P < 0.001) and de-escalation (63.1 ± 39.5 h versus 39.2 ± 25.6 h, P < 0.01) of therapy were shorter in the postimplementation group. TOT for patients with multidrug-resistant organisms (MDROs) was shorter in the postimplementation group (61.8 ± 37.2 h versus 21.9 ± 18.8 h, P < 0.001). TOT was shorter during fully staffed clinical pharmacist hours (30.6 ± 58.9 h versus 19.7 ± 31.7 h, p = 0.014). Implementation of RDT and surveillance software with an ASP decreased TOT for Gram-negative BSIs, including MDROs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Monitoring of procalcitonin (PCT) levels may support appropriate antibiotic discontinuation. The purpose of this study was to determine the current state of PCT monitoring at community hospitals across the United States., Methods: Data from adult patients who were admitted to community hospitals affiliated with a large healthcare system between August 1, 2016, and July 31, 2017, and who received antibiotics were evaluated for the number of PCT levels drawn and the timing between multiple levels. Data from eligible patients were evaluated for the discontinuation of antibiotics after meeting prespecified PCT thresholds for discontinuation of therapy, namely, a PCT measurement of <0.5 μg/L or a decrease of ≥80% from a previous peak value., Results: PCT levels were evaluated for 103,913 patient data sets collected from 136 hospitals. Of these, 70% of the data sets showed a single PCT level drawn, and approximately 30% (30,887) of the data sets showed multiple levels drawn. The first PCT measurement was drawn within 36 hours of antibiotic initiation in 96% of the patients. Of those with multiple levels, 23% (7,089) had levels drawn 24 to 72 hours apart. A small proportion (20% [6,127]) of the patients with multiple levels were eligible for evaluation of appropriate antibiotic discontinuation. Of these, 1,973 (32.2%) patients had antibiotics discontinued within 36 hours of meeting the prespecified PCT thresholds; these patients had a mean duration of antibiotic therapy of 6.1 days with a median of 4.7., Conclusion: Additional standardization of ongoing PCT monitoring and education regarding the appropriate discontinuation of antibiotics when thresholds are reached could aid in the use of this biomarker in support of antibiotic and laboratory stewardship., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess antibiotic selection, administration, and prescribing practices in emergency departments across a large hospital system using evidence-based practices and susceptibility patterns., Methods: This retrospective data review was conducted using health system-level electronic data compiled from 145 emergency departments (EDs) across the United States. Data were examined for national generalizability, most common diagnoses of infectious origin seen in nonadmitted patients in the ED, most commonly administered antibiotics in the ED, and geographically defined areas' unique patterns of antibiotic resistance and susceptibility., Results: More than 627,000 unique patient encounters and 780,000 antibiotic administrations were assessed for trends in patient demographics, antibiotics administered for a diagnosis of infectious origin, and corresponding susceptibility patterns. Results indicated that practices in the EDs of this health system aligned with evidence-based practices for streptococcal pharyngitis, otitis media, cellulitis, and uncomplicated urinary tract infections., Conclusion: These results provide a representative sample of the current state of practices within many EDs across the United States for nonadmitted patients. A similar data reconstruction can be completed by other health systems to assess their prescribing practices in the ED to improve and elevate care for patients visiting the emergency room and treated as outpatients., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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: The Antimicrobial Use (AU) Option of the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN) is a surveillance resource that can provide actionable data for antibiotic stewardship programs. Such data are used to enable measurements of AU across hospitals and before, during, and after stewardship interventions., Methods: We used monthly AU data and annual facility survey data submitted to the NHSN to describe hospitals and neonatal patient care locations reporting to the AU Option in 2017, examine frequencies of most commonly reported agents, and analyze variability in AU rates across hospitals and levels of care. We used results from these analyses in a collaborative project with Vermont Oxford Network to develop neonatal-specific Standardized Antimicrobial Administration Ratio (SAAR) agent categories and neonatal-specific NHSN Annual Hospital Survey questions., Results: As of April 1, 2018, 351 US hospitals had submitted data to the AU Option from at least 1 neonatal unit. In 2017, ampicillin and gentamicin were the most frequently reported antimicrobial agents. On average, total rates of AU were highest in level III NICUs, followed by special care nurseries, level II-III NICUs, and well newborn nurseries. Seven antimicrobial categories for neonatal SAARs were created, and 6 annual hospital survey questions were developed., Conclusions: A small but growing percentage of US hospitals have submitted AU data from neonatal patient care locations to NHSN, enabling the use of AU data aggregated by NHSN as benchmarks for neonatal antimicrobial stewardship programs and further development of the SAAR summary measure for neonatal AU., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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

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

Background: Antimicrobial stewardship is recommended as a crucial mechanism to reduce the emergence of antimicrobial resistance. The purpose of this article was to describe implementation of antimicrobial management programs (AMPs) across a large health system of community hospitals., Methods: The initiative was structured in 4 phases. Although each phase was implemented sequentially, facilities could progress at their own pace. Phase goals needed to be met before moving to the next phase. The 4 phases included preparatory, foundational, clinical care optimization, and refinement. A survey was administered prior to the initiative in 2010, and modified surveys were administered in 2015 and 2017., Results: Stewardship activities improved in most areas of the AMP initiative in 2015, with substantial improvement by 2017. Important changes included an increase in established programs, from 82% in 2010 to 88% and 96% in 2015 and 2017, respectively. Physician Champions increased from 73% in 2010 to 94% in 2017. Advances were made in the use of evidence-based treatment recommendations, antibiogram development, prospective audit and feedback for antimicrobials, tracking of antibiotic usage metrics, and a cost reduction of 40% from baseline., Conclusion: A well-designed, phased approach to implementing AMP can help community hospitals and hospital systems recognize substantial clinical and financial benefits., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

In this multicenter retrospective cohort study of over 1 million patients at 150 US hospitals, proton pump inhibitors increased the odds of a patient having hospital-onset Clostridium difficile infection as did third and fourth generation cephalosporins, carbapenems, and piperacillin/tazobactam. These findings support appropriate prescribing of acid-suppression therapy and high-risk antibiotics.

Data from the National Inpatient Sample show that the decrease in hospitalizations related to methicillin-resistant Staphylococcus aureus (MRSA) infections between 2010 and 2014 primarily reflected declines in skin and soft tissue infections. Hospitalizations related to invasive MRSA remained largely unchanged., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time., Objective: To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals., Design, Setting, and Population: Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014., Exposures: Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance., Main Outcomes and Measures: Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews., Results: A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, -2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (-3.3%/y [95% CI, -5.6% to -1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (-1.3%/y [95% CI, -3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (-7.0%/y [95% CI, -8.8% to -5.2%], P < .001), as did death or discharge to hospice (-4.5%/y [95% CI, -6.1% to -2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23)., Conclusions and Relevance: In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.

Antibiotic stewardship programs (ASPs) improve antibiotic prescribing. Seventy-three percent of US hospitals have <200 beds. Small hospitals (<200 beds) have similar rates of antibiotic prescribing compared to large hospitals, but the majority of small hospitals lack ASPs that satisfy the Centers for Disease Control and Prevention's core elements. All hospitals, regardless of size, are now required to have ASPs by The Joint Commission, and the Centers for Medicare and Medicaid Services has proposed a similar requirement. Very few studies have described the successful implementation of ASPs in small hospitals. We describe barriers commonly encountered in small hospitals when constructing an antibiotic stewardship team, obtaining appropriate metrics of antibiotic prescribing, implementing antibiotic stewardship interventions, obtaining financial resources, and utilizing the microbiology laboratory. We propose potential solutions that tailor stewardship activities to the needs of the facility and the resources typically available., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Challenges 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., Methods: Implementation 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., Results: Implementation 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., Conclusions: Dissemination 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., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Purpose: To describe antimicrobial stewardship programs (ASPs) of acute and long-term acute care (LTAC) hospitals in Houston, Texas., Methods: Two-part survey to clinical pharmacists and pharmacy directors. All acute care and LTAC facilities from the Harris County Medical Society database were invited to participate., Results: In part 1 of the telephone survey, 82 facilities within Houston, Harris county, were contacted by telephone of which 51 responded (response rate: 62%). Of respondents, 55% (n = 28) reported having an active ASP and 8% (n = 4) planned implementation within 12 months. Acute care and LTAC hospitals reported ASPs in 57% and 67% of facilities, respectively. Physician champions were involved in 71% (n = 20) of active ASPs; clinical pharmacists were involved in 75% (n = 21) of programs. In part II, 22 (43%) facilities completed the online survey; postprescription review with feedback was used in facilities with an ASP and medical training program (5 of 5) while formulary restriction was in facilities without stewardship or medical training (6 of 8)., Conclusion: This is the first major survey of ASP in a major metropolitan area. The stewardship effort in the city of Houston is encouraging; we expect the number of stewardship programs in all facilities will continue to rise as focus on antimicrobial resistance grows., (© The Author(s) 2014.)

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.

Background: Urinary 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., Methods: We 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., Findings: 122 646 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)., Interpretation: Universal 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., Funding: HAI 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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Institutional review boards, which are charged with overseeing research, must classify the riskiness of proposed research according to a federal regulation known as the Common Rule (45 CFR 46, Subpart A) and by regulations governing the US Food and Drug Administration codified in 21 CFR 50. If an institutional review board determines that a clinical trial constitutes "minimal risk," there are important practical implications: the institutional review board may then allow a waiver or alteration of the informed consent process; the study may be carried out in certain vulnerable populations; or the study may be reviewed by institutional review boards using an expedited process. However, it is unclear how institutional review boards should assess the risk levels of pragmatic clinical trials. Such trials typically compare existing, widely used medical therapies or interventions in the setting of routine clinical practice. Some of the therapies may be considered risky of themselves but the study comparing them may or may not add to that pre-existing level of risk. In this article, we examine the common interpretations of research regulations regarding minimal-risk classifications and suggest that they are marked by a high degree of variability and confusion, which in turn may ultimately harm patients by delaying or hindering potentially beneficial research. We advocate for a clear differentiation between the risks associated with a given therapy and the incremental risk incurred during research evaluating those therapies as a basic principle for evaluating the risk of a pragmatic clinical trial. We then examine two pragmatic clinical trials and consider how various factors including clinical equipoise, practice variation, research methods such as cluster randomization, and patients' perspectives may contribute to current and evolving concepts of minimal-risk determinations, and how this understanding in turn affects the design and conduct of pragmatic clinical trials., (© The Author(s) 2015.)

Importance: Previous studies suggested that a bundled intervention was associated with lower rates of Staphylococcus aureus surgical site infections (SSIs) among patients having cardiac or orthopedic operations., Objective: To evaluate whether the implementation of an evidence-based bundle is associated with a lower risk of S. aureus SSIs in patients undergoing cardiac operations or hip or knee arthroplasties., Design, Setting, and Participants: Twenty hospitals in 9 US states participated in this pragmatic study; rates of SSIs were collected for a median of 39 months (range, 39-43) during the preintervention period (March 1, 2009, to intervention) and a median of 21 months (range, 14-22) during the intervention period (from intervention start through March 31, 2014)., Interventions: Patients whose preoperative nares screens were positive for methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) were asked to apply mupirocin intranasally twice daily for up to 5 days and to bathe daily with chlorhexidine-gluconate (CHG) for up to 5 days before their operations. MRSA carriers received vancomycin and cefazolin or cefuroxime for perioperative prophylaxis; all others received cefazolin or cefuroxime. Patients who were MRSA-negative and MSSA-negative bathed with CHG the night before and morning of their operations. Patients were treated as MRSA-positive if screening results were unknown., Main Outcomes and Measures: The primary outcome was complex (deep incisional or organ space) S. aureus SSIs. Monthly SSI counts were analyzed using Poisson regression analysis., Results: After a 3-month phase-in period, bundle adherence was 83% (39% full adherence; 44% partial adherence). Overall, 101 complex S. aureus SSIs occurred after 28,218 operations during the preintervention period and 29 occurred after 14,316 operations during the intervention period (mean rate per 10,000 operations, 36 for preintervention period vs 21 for intervention period, difference, -15 [95% CI, -35 to -2]; rate ratio [RR], 0.58 [95% CI, 0.37 to 0.92]). The rates of complex S. aureus SSIs decreased for hip or knee arthroplasties (difference per 10,000 operations, -17 [95% CI, -39 to 0]; RR, 0.48 [95% CI, 0.29 to 0.80]) and for cardiac operations (difference per 10,000 operations, -6 [95% CI, -48 to 8]; RR, 0.86 [95% CI, 0.47 to 1.57])., Conclusions and Relevance: In this multicenter study, a bundle comprising S. aureus screening, decolonization, and targeted prophylaxis was associated with a modest, statistically significant decrease in complex S. aureus SSIs.

Background: Modification 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., Methods: We 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., Findings: Across 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)., Interpretation: Broad-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., Funding: US 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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Overuse and misuse of antibiotics have contributed to the growing problem of antimicrobial resistance and serious side effects including Clostridium difficile infection. The Centers for Disease Control and Prevention estimates that more than 2 million people are infected by multidrug-resistant organisms every year. They propose that promoting antimicrobial stewardship programs (ASP) is an essential component to combat this growing threat. One of the major barriers in implementing effective ASP is the availability of reliable measures which reflect intervention effectiveness. Measuring ASP can be divided into four categories: antimicrobial consumption, process measures, outcome measures, and financial. This article reviews the strengths and weaknesses of the current measures.

Objective: To 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)., Design: Cost analysis using decision modeling., Methods: We 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., Results: In 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., Conclusions: A 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.