Antimicrobial Resistance Patterns of Outpatient Staphylococcus aureus Isolates.

Importance: Oral non-ß-lactam antibiotics are commonly used for empirical therapy of Staphylococcus aureus infections, especially in outpatient settings. However, little is known about potential geographic heterogeneity and temporal trends in the prevalence of S aureus resistance to non-ß-lactams in the US. Objective: To characterize the spatiotemporal trends of resistance to non-ß-lactam antibiotics among community-onset S aureus infections, including regional variation in resistance rates and geographical heterogeneity in multidrug resistance. Design, Setting, and Participants: This cross-sectional study used data from Veterans Health Administration clinics collected from adult outpatients with S aureus infection in the conterminous 48 states and Washington, DC, from January 1, 2010, to December 31, 2019. Data were analyzed from January to November 2023. Exposures: Resistance to lincosamides (clindamycin), tetracyclines, sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX]), and macrolides. Main Outcomes and Measures: Spatiotemporal variation of S aureus resistance to these 4 classes of non-ß-lactam antibiotics, stratified by methicillin-resistant S aureus (MRSA) and methicillin-sensitive S aureus (MSSA), and subdivided by regions of the US (Northeast, Midwest, South, and West). Trend tests and bivariate mapping were used to determine significant changes in resistant proportions over time and identify counties where rates of resistance to multiple non-ß-lactams were high. Results: A total of 382 149 S aureus isolates from 268 214 unique outpatients (mean [SD] age, 63.4 [14.8] years; 252 910 males [94.29%]) were analyzed. There was a decrease in the proportion of MRSA nationwide, from 53.6% in 2010 to 38.8% in 2019. Among MRSA isolates, we observed a significant increase in tetracycline resistance (from 3.6% in 2010 to 12.8% in 2019; P for trend < .001) and TMP-SMX resistance (from 2.6% in 2010 to 9.2% in 2019; P for trend < .001), modest and not significant increases in clindamycin resistance (from 24.2% in 2010 to 30.6% in 2019; P for trend = .34), and a significant decrease in macrolide resistance (from 73.5% in 2010 to 60.2% in 2019; P for trend < .001). Among MSSA isolates, significant upward trends in clindamycin, tetracyclines, and TMP-SMX resistance were observed. For example, tetracycline resistance increased from 3.7% in 2010 to 9.1% in 2019 (P for trend < .001). Regional stratification over time showed that the Northeast had slightly higher rates of clindamycin resistance but lower rates of tetracycline resistance, while the South had notably higher rates of resistance to tetracyclines and TMP-SMX, particularly among MRSA isolates. Bivariate mapping at the county scale did not indicate clear regional patterns of shared high levels of resistance to the 4 classes of antimicrobials studied. Conclusions and Relevance: In this study of outpatient S aureus isolates, MRSA became less common over the 10-year period, and MRSA isolates were increasingly resistant to tetracyclines and TMP-SMX. Geographic analysis indicated no spatial overlap in counties with high rates of resistance to both tetracyclines and TMP-SMX. Examining the regional spatial variation of antibiotic resistance can inform empirical therapy recommendations and help to understand the evolution of S aureus antibiotic resistance mechanisms.

Improving shared decision-making around antimicrobial-prescribing during the end-of-life period: a qualitative study of Veterans, their support caregivers and their providers.

Objective: Antimicrobials are frequently used for palliation during end-of-life care, but adverse effects, such as antimicrobial resistance, are a concern. Shared decision-making is beneficial in end-of-life care conversations to help align antimicrobial-prescribing with patient preferences. However, there is limited data regarding optimal incorporation of antimicrobial-prescribing discussions into shared decision-making conversations. We explored healthcare provider, patient, and support caregiver (eg, family member/friend) perceptions of barriers and facilitators to discussing antimicrobial-prescribing during the end-of-life period. Design: Qualitative study. Participants: Healthcare providers; palliative care/hospice care patients/caregivers. Methods: We conducted semi-structured interviews on shared attitudes/beliefs about antimicrobial-prescribing during end-of-life patient care at one acute-care and one long-term-care facility. Interviews were analyzed for thematic content. Results: Fifteen providers and 13 patients/caregivers completed interviews. Providers recognized the potential benefit of leveraging shared decision-making to guide antimicrobial-prescribing decisions. Barriers included limited face-to-face time with the patient and uncertainty of end-of-life prognosis. Patients/caregivers cited trust, comprehension, and feeling heard as important characteristics which act as facilitators in fostering effective shared decision-making around antimicrobial use. Communication in which providers ensure patients are involved in shared decision-making discussions could be increased to ensure patients and their providers develop a mutually agreeable care plan. Conclusions: Shared decision-making is a practice that can guide antimicrobial-prescribing decisions during end-of-life care, thus potentially minimizing antimicrobial-related adverse effects. Our findings highlight opportunities for increased shared decision-making around antimicrobial use during end-of-life care. Interventions designed to address the identified barriers to shared decision-making have the potential to improve antimicrobial-prescribing practices at end-of-life.

A novel risk-adjusted metric to compare hospitals on their antibiotic-prescribing at hospital discharge.

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 two 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). 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. CONCLUSION: 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.

Assessing the potential for improved predictive capacity of antimicrobial resistance in outpatient Staphylococcus aureus isolates using seasonal and spatial antibiograms.

BACKGROUND: While the use of cumulative susceptibility reports, antibiograms, is recommended for improved empiric therapy and antibiotic stewardship, the predictive ability of antibiograms has not been well-studied. While enhanced antibiograms have been shown to better capture variation in susceptibility profiles by characteristics such as infection site or patient age, the potential for seasonal or spatial variation in susceptibility has not been assessed as important in predicting likelihood of susceptibility. METHODS: Utilizing Staphylococcus aureus isolates obtained in outpatient settings from a nationwide provider of care, the Veterans Health Administration, and a local provider of care, the University of Iowa Hospitals and Clinics, standard, seasonal and spatial antibiograms were created for five commonly used antibiotic classes: cephalosporins, clindamycin, macrolides, tetracycline, trimethoprim/sulfamethoxazole. RESULTS: A total of 338,681 S. aureus isolates obtained in VHA outpatient settings from 2010 to 2019 and 6,817 isolates obtained in UIHC outpatient settings from 2014 to 2019 were used to generate and test antibiograms. Logistic regression modeling determined the capacity of these antibiograms to predict isolate resistance to each antibiotic class. All models had low predictive capacity, with areas under the curve of < 0.7. CONCLUSIONS: Standard antibiograms are poor in predicting S. aureus susceptibility to antibiotics often chosen by clinicians, and seasonal and spatial antibiograms do not provide an improved tool in anticipating non-susceptibility. These findings suggest that further refinements to antibiograms may be necessary to improve their utility in informing choice of effective antibiotic therapy.

Impact of Potential Case Misclassification by Administrative Diagnostic Codes on Outcome Assessment of Observational Study for People Who Inject Drugs.

Introduction: Initiation of medications for opioid use disorder (MOUD) within the hospital setting may improve outcomes for people who inject drugs (PWID) hospitalized because of an infection. Many studies used International Classification of Diseases (ICD) codes to identify PWID, although these may be misclassified and thus, inaccurate. We hypothesized that bias from misclassification of PWID using ICD codes may impact analyses of MOUD outcomes. Methods: We analyzed a cohort of 36 868 cases of patients diagnosed with Staphylococcus aureus bacteremia at 124 US Veterans Health Administration hospitals between 2003 and 2014. To identify PWID, we implemented an ICD code-based algorithm and a natural language processing (NLP) algorithm for classification of admission notes. We analyzed outcomes of prescribing MOUD as an inpatient using both approaches. Our primary outcome was 365-day all-cause mortality. We fit mixed-effects Cox regression models with receipt or not of MOUD during the index hospitalization as the primary predictor and 365-day mortality as the outcome. Results: NLP identified 2389 cases as PWID, whereas ICD codes identified 6804 cases as PWID. In the cohort identified by NLP, receipt of inpatient MOUD was associated with a protective effect on 365-day survival (adjusted hazard ratio, 0.48; 95% confidence interval, .29-.81; P < .01) compared with those not receiving MOUD. There was no significant effect of MOUD receipt in the cohort identified by ICD codes (adjusted hazard ratio, 1.00; 95% confidence interval, .77-1.30; P = .99). Conclusions: MOUD was protective of all-cause mortality when NLP was used to identify PWID, but not significant when ICD codes were used to identify the analytic subjects.

Clinicians' interpretation of thresholds in hospital antibiograms for gram-negative rod infections: A survey and contingent valuation study of hospitalists.

Clinical guidelines suggest that hospital antibiograms are a key component when deciding empiric therapy, but little is known about how often clinicians use antibiograms and how they influence clinicians' empiric therapy decisions. We surveyed hospitalists at seven healthcare systems in the United States on their reported practices related to antibiograms and their hypothetical prescribing for four clinical scenarios associated with gram-negative rod pathogens. Each was given a randomly assigned antibiogram susceptibility percentage, and we used contingent valuation analysis to assess whether the antibiogram susceptibility percentage was associated with prescribing practices. Of the 193 survey responders, only 52 (26.9%) respondents reported using antibiograms more than monthly. Across all four clinical scenarios, there was no evidence that antibiogram susceptibility levels influenced antibiotic prescribing practices. With limited utilization and no evidence that they influenced practice, antibiograms may have a limited role in hospitalist care delivery for common gram-negative rod infections.

Spatiotemporal distribution of community-acquired phenotypic extended-spectrum beta-lactamase Escherichia coli in United States counties, 2010-2019.

Using data from the Veterans' Health Administration from 2010 to 2019, we examined the distribution and prevalence of community-acquired phenotypic extended-spectrum ß-lactamase (ESBL) E. coli in the United States. ESBL prevalence slowly increased during the study period, and cluster analysis showed clustering in both urban and rural locations.

Incidence of Colorectal Cancer in Patients Diagnosed With Pyogenic Liver Abscess.

Importance: Colorectal cancer (CRC) can compromise the mucosal barrier and subsequently allow a route for bacterial invasion into the portal system or systemic circulation. Despite preliminary data suggesting that patients who experienced pyogenic liver abscess (PLA) have higher CRC incidence rates, data from outside the Southeast Asian population are sparse. Objective: To investigate whether there is an association between PLA and the subsequent incidence of diagnosed CRC using the Veterans Health Administration (VHA) cohort. Design, Setting, and Participants: A patient-level matched retrospective cohort study was conducted at 127 VHA hospitals across the US from January 1, 2003, to December 31, 2020. Patients were followed up to 10 years from PLA diagnosis. Data analysis was performed from April 14, 2002, to October 31, 2023. All patients who were admitted to VHA hospitals with a diagnosis of PLA were included. For each patient with PLA, up to 3 controls without diagnosis of PLA, matching age, sex, and health care facility, were selected. Exposure: Pyogenic liver abscess. Main Outcomes and Measures: The primary outcome was CRC diagnosis during the follow-up period. A multivariable Fine-Gray subdistribution regression model with time-dependent coefficient was used to estimate the time-varying hazard ratio (HR) of CRC incidence while accounting for mortality as a competing event. Results: A total of 8286 patients with PLA (male, 96.5%; mean [SD] age, 65.8 [11.9] years) and 23 201 patient-level matched controls (male, 96.3%; mean age, 65.3 [11.7] years) were included. A diagnosis of CRC was found in a significantly higher proportion of patients with PLA compared with controls (1.9% [159 of 8286] vs 0.8% [196 of 23 201]; P < .001). The incidence of CRC was significantly higher among patients with PLA during the first 3 years from PLA diagnosis (HR, 3.64; 95% CI, 2.70-4.91 at 0.5 years; HR, 2.51; 95% CI, 1.93-3.26 at 1 year; HR, 1.74; 95% CI, 1.33-2.28 at 2 years; and HR, 1.41; 95% CI, 1.05-1.89 at 3 years), but not significant after 3 years. This association was not observed among patients whose PLA was likely secondary to cholangitis or cholecystitis (HR, 1.78; 95% CI, 0.89-3.56 at 0.5 years). Conclusions and Relevance: In this patient-level matched retrospective cohort study, a significantly higher incidence of CRC was observed up to 3 years from PLA diagnosis. The findings suggest that offering CRC screening for patients with cryptogenic PLA may be useful, especially patients who have not been screened according to guidelines.

Persistence of potential ST398 MSSA in outpatient settings among US veterans, 2010-2019.

Novel ST398 methicillin susceptible Staphylococcus aureus (MSSA) in the United States was first observed in New York City (2004-2007); its diffusion across the country resulted in changing treatment options. Utilizing outpatient antimicrobial susceptibility data from the Veterans Health Administration from 2010 to 2019, the spatiotemporal prevalence of potential ST398 MSSA is documented.

Diagnostic Accuracy of Hospital Antibiograms in Predicting the Risk of Antimicrobial Resistance in Enterobacteriaceae Isolates: A Nationwide Multicenter Evaluation at the Veterans Health Administration.

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.

Perceptions of an automated benchmarking dashboard for antimicrobial stewardship programs among antimicrobial stewards within the veterans' health administration: a multicenter qualitative study.

Objective: To evaluate the impact of a multicenter, try automated dashboard on ASP activities and its acceptance among ASP leaders. Design: Frontline stewards were asked to participate in semi-structured interviews before and after implementation of a web-based ASP information dashboard providing risk-adjusted benchmarking, longitudinal trends, and analysis of antimicrobial usage patterns at each facility. Setting: The study was performed at Iowa City VA Health Care System. Participants: ASP team members from nine medical centers in the VA Midwest Health Care Network (VISN 23). Methods: Semi-structured interviews were conducted pre- and post-implementation, with interview guides informed by clinical experiences and the Consolidated Framework for Implementation Research (CFIR). Participants evaluated the dashboard's ease of use, applicability to ongoing ASP activities, perceived validity and reliability, and relative advantage over other ASP monitoring systems. Results: Compared to established stewardship data collection and reporting methods, participants found the dashboard more intuitive and accessible, allowing them to reduce dependence on other systems and staff to obtain and share data. Standardized and risk-adjusted rankings were largely accepted as a valuable benchmarking method; however, participants felt their facility's characteristics significantly influenced the rankings' validity. Participants recognized staffing, training, and uncertainty with using the dashboard as an intervention tool as barriers to consistent and comprehensive dashboard implementation. Conclusions: Participants generally accepted the dashboard's risk-adjusted metrics and appreciated its usability. While creating automated tools to rigorously benchmark antimicrobial use across hospitals can be helpful, the displayed metrics require further validation, and the longitudinal utility of the dashboard warrants additional study.

Impacts of Hurricane Matthew Exposure on Infections and Antimicrobial Prescribing in North Carolina Veterans.

The impact of hurricane-related flooding on infectious diseases in the US is not well understood. Using geocoded electronic health records for 62,762 veterans living in North Carolina counties impacted by Hurricane Matthew coupled with flood maps, we explore the impact of hurricane and flood exposure on infectious outcomes in outpatient settings and emergency departments as well as antimicrobial prescribing. Declines in outpatient visits and antimicrobial prescribing are observed in weeks 0-2 following the hurricane as compared with the baseline period and the year prior, while increases in antimicrobial prescribing are observed 3+ weeks following the hurricane. Taken together, hurricane and flood exposure appear to have had minor impacts on infectious outcomes in North Carolina veterans, not resulting in large increases in infections or antimicrobial prescribing.

The association of infectious diseases consultation and 30-day mortality rates among veterans with enterococcal bacteraemia: a propensity score-matched retrospective cohort study.

OBJECTIVES: Infectious disease consultation (IDC) has been associated with improved outcomes in several infections, but the benefit of IDC among patients with enterococcal bacteraemia has not been fully evaluated. METHODS: We performed a 1:1 propensity score-matched retrospective cohort study evaluating all patients with enterococcal bacteraemia at 121 Veterans Health Administration acute-care hospitals from 2011 to 2020. The primary outcome was 30-day mortality. We performed conditional logistic regression to calculate the OR to determine the independent association of IDC and 30-day mortality adjusted for vancomycin susceptibility and the primary source of bacteraemia. RESULTS: A total of 12,666 patients with enterococcal bacteraemia were included; 8400 (63.3%) had IDC, and 4266 (36.7%) did not have IDC. Two thousand nine hundred seventy-two patients in each group were included after propensity score matching. Conditional logistic regression revealed that IDC was associated with a significantly lower 30-day mortality rate compared with patients without IDC (OR = 0.56; 95% CI, 0.50-0.64). The association of IDC was observed irrespective of vancomycin susceptibility, and when the primary source of bacteraemia was a urinary tract infection, or from an unknown primary source. IDC was also associated with higher appropriate antibiotic use, blood culture clearance documentation, and the use of echocardiography. DISCUSSION: Our study suggests that IDC was associated with improved care processes and 30-day mortality rates among patients with enterococcal bacteraemia. IDC should be considered for patients with enterococcal bacteraemia.

Tracking antimicrobial stewardship activities beyond days of therapy (DOT): Comparison of days of antibiotic spectrum coverage (DASC) and DOT at a single center.

Even though antimicrobial days of therapy did not significantly decrease during a period of robust stewardship activities at our center, we detected a significant downward trend in antimicrobial spectrum, as measured by days of antibiotic spectrum coverage (DASC). The DASC metric may help more broadly monitor the effect of stewardship activities.

Decline in oral antimicrobial prescription in the outpatient setting after nationwide implementation of financial incentives and provider education: An interrupted time-series analysis.

OBJECTIVES: To assess the impact of nationwide outpatient antimicrobial stewardship interventions in the form of financial incentives for providers and provider education when antimicrobials are deemed unnecessary for uncomplicated respiratory infections and acute diarrhea. METHODS: We collected data from a large claims database from April 2013 through March 2020 and performed a quasi-experimental, interrupted time-series analysis. The outcome of interest was oral antimicrobial prescription rate defined as the number of monthly antimicrobial prescriptions divided by the number of outpatient visits each month. We examined the effects of financial incentive to providers (ie, targeted prescriptions for those aged ≤2 years) and provider education (ie, targeted prescriptions for those aged ≥6 years) on the overall antimicrobial prescription rates and how these interventions affected different age groups before and after their implementation. RESULTS: In total, 21,647,080 oral antimicrobials were prescribed to 2,920,381 unique outpatients during the study period. At baseline, prescription rates for all age groups followed a downward trend throughout the study period. Immediately after the financial incentive implementation, substantial reductions in prescription rates were observed among only those aged 0-2 years (-47.5 prescriptions per 1,000 clinic visits each month; 95% confidence interval, -77.3 to -17.6; P = .003), whereas provider education immediately reduced prescription rates in all age groups uniformly. These interventions did not affect the long-term trend for any age group. CONCLUSION: These results suggest that the nationwide implementation of financial incentives and provider education had an immediate effect on the antimicrobial prescription but no long-term effect.

County-level spatiotemporal distribution of fluoroquinolone-resistant Enterobacteriaceae in outpatient settings of the Veterans' Health Administration, 2000-2017.

Fluoroquinolone resistance among Enterobacteriaceae is a notable challenge for appropriate empiric therapy in outpatient settings. We describe the spatial distribution of fluoroquinolone resistance and its chronological change between 2000 and 2017 in the nationwide Veterans' Health Administration system. We found spatially concentrated increasing prevalence in the 2000s, followed by spatial dispersion in the 2010s.