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Background: Antibiotic overuse at hospital discharge is common, but there is no metric to evaluate hospital performance at this transition of care. We built a risk-adjusted metric for comparing hospitals on their overall post-discharge antibiotic use., Methods: This was a retrospective study across all acute-care admissions within the Veterans Health Administration during 2018-2021. For patients discharged to home, we collected data on antibiotics and relevant covariates. We built a zero-inflated, negative, binomial mixed model with 2 random intercepts for each hospital to predict post-discharge antibiotic exposure and length of therapy (LOT). Data were split into training and testing sets to evaluate model performance using absolute error. Hospital performance was determined by the predicted random intercepts., Results: 1 804 300 patient-admissions across 129 hospitals were included. Antibiotics were prescribed to 41.5% while hospitalized and 19.5% at discharge. Median LOT among those prescribed post-discharge antibiotics was 7 (IQR, 4-10) days. The predictive model detected post-discharge antibiotic use with fidelity, including accurate identification of any exposure (area under the precision-recall curve = 0.97) and reliable prediction of post-discharge LOT (mean absolute error = 1.48). Based on this model, 39 (30.2%) hospitals prescribed antibiotics less often than expected at discharge and used shorter LOT than expected. Twenty-eight (21.7%) hospitals prescribed antibiotics more often at discharge and used longer LOT., Conclusions: A model using electronically available data was able to predict antibiotic use prescribed at hospital discharge and showed that some hospitals were more successful in reducing antibiotic overuse at this transition of care. This metric may help hospitals identify opportunities for improved antibiotic stewardship at discharge., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Many clinical guidelines recommend that clinicians use antibiograms to inform empiric antimicrobial therapy. However, hospital antibiograms are typically generated by crude aggregation of microbiologic data, and little is known about an antibiogram's reliability in predicting antimicrobial resistance (AMR) risk at the patient-level. We aimed to assess the diagnostic accuracy of antibiograms as a tool for selecting empiric therapy for Escherichia coli and Klebsiella spp. for individual patients., Methods: We retrospectively generated hospital antibiograms for the nationwide Veterans Health Administration (VHA) facilities from 2000 to 2019 using all clinical culture specimens positive for E. coli and Klebsiella spp., then assessed the diagnostic accuracy of an antibiogram to predict resistance for isolates in the following calendar year using logistic regression models and predefined 5-step interpretation thresholds., Results: Among 127 VHA facilities, 1 484 038 isolates from 704 779 patients for E. coli and 671 035 isolates from 340 504 patients for Klebsiella spp. were available for analysis. For E. coli and Klebsiella spp., the discrimination abilities of hospital-level antibiograms in predicting individual patient AMR were mostly poor, with the areas under the receiver operating curve at 0.686 and 0.715 for ceftriaxone, 0.637 and 0.675 for fluoroquinolones, and 0.576 and 0.624 for trimethoprim-sulfamethoxazole, respectively. The sensitivity and specificity of the antibiogram varied widely by antimicrobial groups and interpretation thresholds with substantial trade-offs., Conclusions: Conventional hospital antibiograms for E. coli and Klebsiella spp. have limited performance in predicting AMR for individual patients, and their utility in guiding empiric therapy may be low., Competing Interests: Potential conflicts of interest. M. G. and D. L. report grants or contracts from Merck Investigator Study Program (paid to institution). D. L. also reports grants or contracts from Centers and Disease Control and Prevention (CDC) Epicenter Grant (grant number J207400-G) (Herwaldt) and VA Health Services Research and Development Service (HSR&D) Investigator Initiated Research (IIR) (grant number 20–280); support for attending meetings and/or travel as a Speaker at SHEA Spring 2023. M. G. also reports the CDC Epicenter Grant (grant number J207400-G) (Herwaldt). E. N. P. reports grants or contracts paid to institution from VA-CDC Practice-Based Research Network program and VA HSR&D (grant numbers CIN 13-412 and QUE 15-269). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of infectious diseases consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC., Competing Interests: Potential conflicts of interest. D. J. L. receives funding from VA HSR&D, Centers for Disease Control and Prevention (CDC) and Merck Investigator Studies Program. A. N. M. reports payment for expert testimony outside of the submitted work; shares of Pfizer pharmaceuticals; membership of Society Healthcare Epidemiology of America (SHEA) Board of Trustees (2020–2022); board membership of Michigan Infectious Diseases Society; consultancy for and grant funding from Michigan Department of Health and Human Services. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Days of therapy (DOT), the most widely used benchmarking metric for antibiotic consumption, may not fully measure stewardship efforts to promote use of narrow-spectrum agents and may inadvertently discourage the use of combination regimens when single-agent alternatives have greater adverse effects. To overcome the limitations of DOT, we developed a novel metric, days of antibiotic spectrum coverage (DASC), and compared hospital performances using this novel metric with DOT., Methods: We evaluated 77 antibiotics in 16 categories of antibacterial activity to develop our spectrum scoring system. DASC was then calculated as cumulative daily antibiotic spectrum coverage (ASC) scores. To compare hospital benchmarking using DOT and DASC, we conducted a retrospective cohort study of adult patients admitted to acute care units within the Veterans Health Administration system in 2018. Antibiotic administration data were aggregated to calculate each hospital's DOT and DASC per 1000 days present (DP) for ranking., Results: The ASC score for each antibiotic ranged from 2 to 15. There was little correlation between DOT per 1000 DP and DASC per DOT, indicating that lower antibiotic consumption at a hospital does not necessarily mean more frequent use of narrow-spectrum antibiotics. The differences in each hospital's ranking between DOT and DASC per 1000 DP ranged from -29.0% to 25.0%, respectively, with 27 hospitals (21.8%) having differences >10%., Conclusions: We propose a novel composite metric for antibiotic stewardship, DASC, that combines consumption and spectrum as a potential replacement for DOT. Further studies are needed to evaluate whether benchmarking using the DASC will improve evaluations of stewardship., Competing Interests: Potential conflicts of interest. E. N. P. reports support from the US Department of Veterans Affairs (grants QUE 15-269 and RVR 19-477), outside the conduct of the study. D. J. D. reports grants to their institution from bioMerieux, to support clinical trials, and individual payments from OpGen, for consulting on novel diagnostics, and JMI Laboratories, for consulting on antibiotic resistance surveillance studies. D. I. reports payments to their institution from Gilead Sciences, for clinical trials on remdesivir, and from Leidos, for Adaptive COVID-19 Treatment Trial 3 and Adaptive COVID-19 Treatment Trial 4, clinical trials sponsored by the National Institutes of Health; D. I. also serves on the data and safety monitoring board for Evergreen Pharma. P. K. reports grants from Accelerate Diagnostics to University of Iowa Hospitals & Clinics principal investigators to support clinical study, outside the submitted work, and reports serving on an advisory panel for Gilead Sciences, on remdesivir in coronavirus disease 2019. M. G. reports support for the present study from the VHA Patient Safety Center for Inquiry program. D. J. L. reports support from the Health Services Research and Development Service (grant 20-240 [coinvestigator], career development award 16-204, and grant D 20-280 [principal investigator: D. J. L.]), the Centers for Diseases Control and Prevention EpiCenter (grant J207400-G; coinvestigator), and the Merck Investigator Studies Program. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Empiric antimicrobial therapy for healthcare-acquired infections often includes vancomycin plus an anti-pseudomonal beta-lactam (AP-BL). These agents vary in risk for adverse events, including acute kidney injury (AKI) and Clostrioides difficile infection (CDI). Studies have only examined these risks separately; thus, our objective was to evaluate AKI and CDI risks simultaneously with AP-BL in the same patient cohort., Methods: This retrospective cohort study included 789 200 Veterans Health Administration medical admissions from 1 July 2010 through 30 June 2016. The antimicrobials examined were vancomycin, cefepime, piperacillin/tazobactam, and meropenem. Cox proportional hazards regression was used to contrast risks for AKI and CDI across individual target antimicrobials and vancomycin combination therapies, including adjustment for known confounders., Results: With respect to the base rate of AKI among patients who did not receive a target antibiotic (4.6%), the adjusted hazards ratios for piperacillin/tazobactam, cefepime, and meropenem were 1.50 (95% CI: 1.43-1.54), 1.00 (.95-1.05), 0.92 (.83-1.01), respectively. Co-administration of vancomycin increased AKI rates (data not shown). Similarly, against the base rate of CDI (0.7%), these ratios were 1.21 (1.07-1.36), 1.89 (1.62-2.20), and 1.99 (1.55-2.56), respectively. Addition of vancomycin had minimal impact on CDI rates (data not shown)., Conclusions: Piperacillin/tazobactam increased AKI risk, which was exacerbated by concurrent vancomycin. Cefepime and meropenem increased CDI risk relative to piperacillin/tazobactam. Clinicians should consider the risks and benefits of AP-BL when selecting empiric regimens. Further well-designed studies evaluating the global risks of AP-BL and patient specific characteristics that can guide empiric selection are needed., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Candidemia is one of the most common causes of nosocomial bloodstream infections, but the impacts of factors affecting its incidence have not been evaluated., Methods: We analyzed a retrospective cohort of all candidemia patients at 130 acute care hospitals in the Veterans Health Administration (VHA) system from January 2000 through December 2017. Cases were classified as hospital-onset (HO) and non-hospital-onset (NHO). We used Joinpoint regression analysis to assess temporal associations between significant changes in candidemia incidence rates and guidelines or horizontal infection control (IC) interventions., Results: Over 18 years, 17 661 candidemia episodes were identified. Incidence rates of HO cases were increasing until the mid-2000s, followed by a sustained decline, while NHO cases showed a steady decline. The first change in HO candidemia incidence rates (August 2004 [95% confidence interval {CI}, February 2003-April 2005]) was preceded by the publication of catheter-related bloodstream infection (CRBSI) prevention guidelines and the CRBSI surveillance initiation. The second (September 2007 [95% CI, September 2006-June 2009]) had close temporal proximity to the expansion of IC resources within the VHA system. Collectively, these trend changes resulted in a 77.1% reduction in HO candidemia incidence rates since its peak in 2004., Conclusions: A substantial and sustained systemwide reduction in candidemia incidence rates was observed after the publication of guidelines, VHA initiatives about CRBSI reporting and education on CRBSI prevention, and the systemwide expansion of IC resources., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: The optimal method for implementing hospital-level restrictions for antibiotics that carry a high risk of Clostridioides difficile infection has not been identified. We aimed to explore barriers and facilitators to implementing restrictions for fluoroquinolones and third/fourth-generation cephalosporins., Methods: This mixed-methods study across a purposeful sample of 15 acute-care, geographically dispersed Veterans Health Administration hospitals included electronic surveys and semi-structured interviews (September 2018 to May 2019). Surveys on stewardship strategies were administered at each hospital and summarized with descriptive statistics. Interviews were performed with 30 antibiotic stewardship programme (ASP) champions across all 15 sites and 19 additional stakeholders at a subset of 5 sites; transcripts were analysed using thematic content analysis., Results: The most restricted agent was moxifloxacin, which was restricted at 12 (80%) sites. None of the 15 hospitals restricted ceftriaxone. Interviews identified differing opinions on the feasibility of restricting third/fourth-generation cephalosporins and fluoroquinolones. Some participants felt that restrictions could be implemented in a way that was not burdensome to clinicians and did not interfere with timely antibiotic administration. Others expressed concerns about restricting these agents, particularly through prior approval, given their frequent use, the difficulty of enforcing restrictions and potential unintended consequences of steering clinicians towards non-restricted antibiotics. A variety of stewardship strategies were perceived to be effective at reducing the use of these agents., Conclusions: Across 15 hospitals, there were differing opinions on the feasibility of implementing antibiotic restrictions for third/fourth-generation cephalosporins and fluoroquinolones. While the perceived barrier to implementing restrictions was frequently high, many hospitals were effectively using restrictions and reported few barriers to their use., (Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Many US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist., Methods: This retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions., Results: Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum β-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99)., Conclusions: Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Objectives: Carbapenems are an important target for antimicrobial stewardship (AS) efforts. In this study, we sought to compare different hospital-based strategies for improving carbapenem use., Methods: We analysed a cohort of all patients hospitalized at Veterans Health Administration (VHA) acute care hospitals during 2016 and a mandatory survey that characterized each hospital's carbapenem-specific AS strategy into one of three types: no strategy (NS), prospective audit and feedback (PAF) or restrictive policies (RP). Carbapenem use was compared using risk-adjusted generalized estimating equations that accounted for clustering within hospitals. Two infectious disease (ID) physicians independently performed manual chart reviews in 425 randomly selected cases. Auditors assessed carbapenem appropriateness with an assessment score on Day 4 of therapy., Results: There were 429 062 admissions in 90 sites (24 NS, 8 PAF, 58 RP). Carbapenem use was lower at PAF than NS sites [rate ratio (RR) 0.6 (95% CI 0.4-0.9); P = 0.01] but similar between RP and NS sites. Carbapenem prescribing was considered appropriate/acceptable in 215 (50.6%) of the reviewed cases. Assessment scores were lower (i.e. better) at RP than NS sites (mean 2.3 versus 2.7; P < 0.01) but did not differ significantly between NS and PAF sites. ID consultations were more common at PAF/RP than NS sites (51% versus 29%; P < 0.01). ID consultations were associated with lower (i.e. better) assessment scores (mean 2.3 versus 2.6; P < 0.01)., Conclusions: In this VHA cohort, PAF strategies were associated with lower carbapenem use and ID consultation and RP strategies were associated with more appropriate carbapenem prescribing. AS and ID consultations may work complementarily and hospitals could leverage both to optimize carbapenem use., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA BSI) usually receive initial treatment with vancomycin but may be switched to daptomycin for definitive therapy, especially if treatment failure is suspected. Our objective was to evaluate the effectiveness of switching from vancomycin to daptomycin compared with remaining on vancomycin among patients with MRSA BSI., Methods: Patients admitted to 124 Veterans Affairs Hospitals who experienced MRSA BSI and were treated with vancomycin during 2007-2014 were included. The association between switching to daptomycin and 30-day mortality was assessed using Cox regression models. Separate models were created for switching to daptomycin any time during the first hospitalization and for switching within 3 days of receiving vancomycin., Results: In total, 7411 patients received vancomycin for MRSA BSI. Also, 606 (8.2%) patients switched from vancomycin to daptomycin during the first hospitalization, and 108 (1.5%) switched from vancomycin to daptomycin within 3 days of starting vancomycin. In the multivariable analysis, switching to daptomycin within 3 days was significantly associated with lower 30-day mortality (hazards ratio [HR] = 0.48; 95% confidence interval [CI]: .25, .92). However, switching to daptomycin at any time during the first hospitalization was not significantly associated with 30-day mortality (HR: 0.87; 95% CI: .69, 1.09)., Conclusions: Switching to daptomycin within 3 days of initial receipt of vancomycin is associated with lower 30-day mortality among patients with MRSA BSI. This benefit was not seen when the switch occurred later. Future studies should prospectively assess the benefit of early switching from vancomycin to other anti-MRSA antibiotics., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Despite increasing awareness of harms, fluoroquinolones are still frequently prescribed to inpatients and at hospital discharge. Our goal was to describe fluoroquinolone prescribing at hospital discharge across the Veterans Health Administration (VHA) and to contrast the volume and appropriateness of fluoroquinolone prescribing across 3 antimicrobial stewardship strategy types., Methods: We analyzed a retrospective cohort of patients hospitalized at 122 VHA acute-care hospitals during 2014-2016. Data from a mandatory VHA survey were used to identify 9 hospitals that self-reported 1 of 3 strategies for optimizing fluoroquinolone prescribing: prospective audit and feedback (PAF), restrictive policies (RP), and no strategy. Manual chart reviews to assess fluoroquinolone appropriateness at hospital discharge (ie, postdischarge) were performed across the 9 hospitals (3 hospitals and 125 cases per strategy type)., Results: There were 1.7 million patient admissions. Overall, there were 1 727 478 fluoroquinolone days of therapy (DOTs), with 674 918 (39.1%) DOTs prescribed for inpatients and 1 052 560 (60.9%) DOTs prescribed postdischarge. Among the 9 reviewed hospitals, postdischarge fluoroquinolone exposure was lower at hospitals using RP, compared to no strategy (3.8% vs 9.3%, respectively; P = .012). Postdischarge fluoroquinolones were deemed inappropriate in 154 of 375 (41.1%) patients. Fluoroquinolones were more likely to be inappropriate at hospitals without a strategy (52.8%) versus those using either RP or PAF (35.2%; P = .001)., Conclusions: In this retrospective cohort, the majority of fluoroquinolone DOTs occurred after hospital discharge. A large proportion of postdischarge fluoroquinolone prescriptions were inappropriate, especially in hospitals without a strategy to manage fluoroquinolone prescribing. Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone prescribing should also focus on antimicrobial prescribing at hospital discharge., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: To treat patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections, β-lactams are recommended for definitive therapy; however, the comparative effectiveness of individual β-lactams is unknown. This study compared definitive therapy with cefazolin vs nafcillin or oxacillin among patients with MSSA infections complicated by bacteremia., Methods: This retrospective study included patients admitted to 119 Veterans Affairs hospitals from 2003 to 2010. Patients were included if they had a blood culture positive for MSSA and received definitive therapy with cefazolin, nafcillin, or oxacillin. Cox proportional hazards regression and ordinal logistic regression were used to identify associations between antibiotic therapy and mortality or recurrence. A recurrent infection was defined as a MSSA blood culture between 45 and 365 days after the first MSSA blood culture., Results: Of 3167 patients, 1163 (37%) patients received definitive therapy with cefazolin. Patients who received cefazolin had a 37% reduction in 30-day mortality (hazard ratio [HR], 0.63; 95% confidence interval [CI], .51-.78) and a 23% reduction in 90-day mortality (HR, 0.77; 95% CI, .66-.90) compared with patients receiving nafcillin or oxacillin, after controlling for other factors. The odds of recurrence (odds ratio, 1.13; 95% CI, .94-1.36) were similar among patients who received cefazolin compared with patients who received nafcillin or oxacillin, after controlling for other factors., Conclusions: In this large, multicenter study, patients who received cefazolin had a lower risk of mortality and similar odds of recurrent infections compared with nafcillin or oxacillin for MSSA infections complicated by bacteremia. Physicians might consider definitive therapy with cefazolin for these infections., (© 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.)

Background: The Veterans Health Administration (VHA) introduced the Methicillin-Resistant Staphylococcus aureus (MRSA) Prevention Initiative in March 2007. Although the initiative has been perceived as a vertical intervention focusing on MRSA, it also expanded infection prevention and control programs and resources. We aimed to assess the horizontal effect of the initiative on hospital-onset (HO) gram-negative rod (GNR) bacteremia., Methods: This retrospective cohort included all patients who had HO bacteremia due to Escherichia coli, Klebsiella species, or Pseudomonas aeruginosa at 130 VHA facilities from January 2003 to December 2013. The effects were assessed using segmented linear regression with autoregressive error models, incorporating autocorrelation, immediate effect, and time before and after the initiative. Community-acquired (CA) bacteremia with same species was also analyzed as nonequivalent dependent controls., Results: A total of 11 196 patients experienced HO-GNR bacteremia during the study period. There was a significant change of slope in HO-GNR bacteremia incidence rates from before the initiative (+0.3%/month) to after (-0.4%/month) (P < .01), while CA GNR incidence rates did not significantly change (P = .08). Cumulative effect of the intervention on HO-GNR bacteremia incidence rates at the end of the study period was estimated to be -43.2% (95% confidence interval, -51.6% to -32.4%). Similar effects were observed in subgroup analyses of each species and antimicrobial susceptibility profile., Conclusions: Within 130 VHA facilities, there was a sustained decline in HO-GNR bacteremia incidence rates after the implementation of the MRSA Prevention Initiative. As these organisms were not specifically targeted, it is likely that horizontal components of the initiative contributed to this decline., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)