Blood culture algorithm implementation in emergency department patients as a diagnostic stewardship intervention.

OBJECTIVE: Blood cultures (BCx) are important for selecting appropriate antibiotic treatment. Ordering BCx for conditions with a low probability of bacteremia has limited utility, thus improved guidance for ordering BCx is needed. Inpatient studies have implemented BCx algorithms, but no studies examine the intervention in an Emergency Department (ED) setting. METHODS: We performed a quasi-experimental pre and postintervention study from January 12, 2020, to October 31, 2023, at a single academic adult ED and implemented a BCx algorithm. The primary outcome was the blood culture event rates (BCE per 100 ED admissions) pre and postintervention. Secondary outcomes included adverse event rates (30-day ED and hospital readmission and antibiotic days of therapy). Seven ED physicians and APP reviewed BCx for appropriateness, with monthly feedback provided to ED leadership and physicians. RESULTS: After the BCx algorithm implementation, the BCE rate decreased from 12.17 BCE/100 ED admissions to 10.50 BCE/100 ED admissions. Of the 3,478 reviewed BCE, we adjudicated 2,153 BCE (62%) as appropriate, 653 (19%) as inappropriate, and 672 (19%) as uncertain. Adverse safety events were not statistically different pre and postintervention. CONCLUSIONS: Implementation of an ED BCx algorithm demonstrated a reduction in BCE, without increased adverse safety events. Future studies should compare outcomes of BCx algorithm implementation in a community hospital ED without intensive chart review.

Clinical outcomes in patients with piperacillin/ tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection.

BACKGROUND: A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. OBJECTIVES: We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. METHODS: We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. RESULTS: Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5-71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0-16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30-1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. CONCLUSIONS: These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone.

Antimicrobial stewardship knowledge, attitudes, and practices (KAP) among nurses.

We performed a knowledge, attitudes, and practice (KAP) survey of bedside nurses to evaluate perceptions of antimicrobial use and aid in the design of nursing-based antimicrobial stewardship interventions. The survey highlighted discrepancies in knowledge and practice as well as opportunities to improve communication with nursing colleagues.

Teams in Transition: Increasing Role of Advanced Practice Providers in Antimicrobial Use and Infectious Diseases Consultation.

Background: Advanced practice providers (APPs) have taken on increasing responsibilities as primary team members in acute care hospitals, but the impact of this practice shift on antimicrobial prescribing and infectious diseases (ID) consultation requests is unknown. Here we describe longitudinal trends in antimicrobial days of therapy (DOT) and ID consultation by attributed provider type in 3 hospitals. Methods: We performed a retrospective time series analysis of antimicrobial use and ID consultation from July 2015 to June 2022 at a major university hospital and 2 community hospitals. We evaluated antimicrobial DOT and ID consultation over time and assessed attribution to 3 groups of providers: attending physicians, trainees, and APPs. We used multinomial logistic regression to measure changes in percentage of DOT and ID consultation across the clinician groups over time using physicians as the referent. Results: Baseline distribution of antimicrobial DOT and ID consultation varied by practice setting, but all subgroups showed increases in the proportion attributable to APPs. Large increases were seen in the rate of ID consultation, increasing by >30% during the study period. At our university hospital, by study end >40% of new ID consults and restricted antimicrobial days were attributed to APPs. Conclusions: Hospitals had differing baseline patterns of DOT attributed to provider groups, but all experienced increases in DOT attributed to APPs. Similar increases were seen in changes to ID consultation. APPs have increasing involvement in antimicrobial use decisions in the inpatient setting and should be engaged in future antimicrobial stewardship initiatives.

The devil's in the defaults: An interrupted time-series analysis of the impact of default duration elimination on exposure to fluoroquinolone therapy.

OBJECTIVE: To determine whether removal of default duration, embedded in electronic prescription (e-script), influenced antibiotic days of therapy. DESIGN: Interrupted time-series analysis. SETTING: The study was conducted across 2 community hospitals, 1 academic hospital, 3 emergency departments, and 86 ambulatory clinics. PATIENTS: Adults prescribed a fluoroquinolone with a duration <31 days. INTERVENTIONS: Removal of standard 10-day fluoroquinolone default duration and addition of literature-based duration guidance in the order entry on December 19, 2017. The study period included data for 12 months before and after the intervention. RESULTS: The study included 35,609 fluoroquinolone e-scripts from the preintervention period and 31,303 fluoroquinolone e-scripts from the postintervention period, accounting for 520,388 cumulative fluoroquinolone DOT. Mean durations before and after the intervention were 7.8 (SD, 4.3) and 7.7 (SD, 4.5), a nonsignificant change. E-scripts with a 10-day duration decreased prior to and after the default removal. The inpatient setting showed a significant 8% drop in 10-day e-scripts after default removal and a reduced median duration by 1 day; 10-day scripts declined nonsignificantly in ED and ambulatory settings. In the ambulatory settings, both 7- and 14-day e-script durations increased after default removal. CONCLUSION: Removal of default 10-day antibiotic durations did not affect overall mean duration but did shift patterns in prescribing, depending on practice setting. Stewardship interventions must be studied in the context of practice setting. Ambulatory stewardship efforts separate from inpatient programs are needed because interventions cannot be assumed to have similar effects.

Penicillin Allergy Impact and Management.

There is international evidence that penicillin allergies are associated with inferior prescribing and patient outcomes. A host of tools now exist from assessment (risk assessment tools, clinical decision rules) to delabeling (the removal of a beta-lactam allergy via testing or medical reconciliation) to reduce the impact of these "labels" in the hospital and community setting, as a primary antimicrobial stewardship intervention.

Optimizing reflex urine cultures: Using a population-specific approach to diagnostic stewardship.

BACKGROUND: Clinicians and laboratories routinely use urinalysis (UA) parameters to determine whether antimicrobial treatment and/or urine cultures are needed. Yet the performance of individual UA parameters and common thresholds for action are not well defined and may vary across different patient populations. METHODS: In this retrospective cohort study, we included all encounters with UAs ordered 24 hours prior to a urine culture between 2015 and 2020 at 3 North Carolina hospitals. We evaluated the performance of relevant UA parameters as potential outcome predictors, including sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also combined 18 different UA criteria and used receiver operating curves to identify the 5 best-performing models for predicting significant bacteriuria (≥100,000 colony-forming units of bacteria/mL). RESULTS: In 221,933 encounters during the 6-year study period, no single UA parameter had both high sensitivity and high specificity in predicting bacteriuria. Absence of leukocyte esterase and pyuria had a high NPV for significant bacteriuria. Combined UA parameters did not perform better than pyuria alone with regard to NPV. The high NPV ≥0.90 of pyuria was maintained among most patient subgroups except females aged ≥65 years and patients with indwelling catheters. CONCLUSION: When used as a part of a diagnostic workup, UA parameters should be leveraged for their NPV instead of sensitivity. Because many laboratories and hospitals use reflex urine culture algorithms, their workflow should include clinical decision support and or education to target symptomatic patients and focus on populations where absence of pyuria has high NPV.

Comparison of Open-Access, Trough-Only Online Calculators Versus Trapezoidal Method for Calculation of Vancomycin Area Under the Curve (AUC).

BACKGROUND: Vancomycin area-under-the-curve (AUC) monitoring is associated with reduced nephrotoxicity but may increase cost and workload for personnel compared to trough monitoring. OBJECTIVE: The purpose of this study was to compare the accuracy of vancomycin AUC calculated by open-access, online, trough-only calculators to AUCs calculated by the trapezoidal method (TM) using peak and trough concentrations. METHODS: This retrospective, multi-center study included adults ≥18 years old with stable renal function who received vancomycin with steady-state peak and trough concentrations. Areas under the curve calculated by TM were compared to AUCs calculated by 3 online calculators using trough-only options for calculation: ClinCalc, VancoVanco, and VancoPK. The primary outcome was actual difference in AUC between TM and the online calculators. Secondary outcomes were percent difference in AUC and clinical alignment in dose adjustments between methods. RESULTS: Seventy patients were included for analysis. There was a statistically significant difference in AUC between TM and ClinCalc (median actual difference: -52, P < 0.001) and VancoVanco (median actual difference: 95, P < 0.001), whereas there was no significant difference between TM and VancoPK (median actual difference: -0.8, P = 0.827). Discordant dose adjustments were indicated when comparing ClinCalc, VancoVanco, and VancoPK to TM in 28%, 36%, and 12% of cases, respectively. CONCLUSION: The AUC calculator most closely aligned with TM was VancoPK, whereas other included calculators were statistically different. Owing to the cost and complexity of obtaining multiple levels, our findings support using a single steady-state trough using VancoPK as an alternative to TM for calculation of vancomycin AUC.

Measuring empiric antibiotic spectrum-A journey through space and time.

OBJECTIVES: The typical 5-day work week affects healthcare outcomes. Structured work hours have also been implicated in antimicrobial prescribing choice. We developed a visualization tool to aid in evaluating breadth of antibiotic use in various time (day of week and hour of day) and space (patient location) combinations. METHODS: We evaluated antibiotic administration data from a tertiary-care academic medical center between July 1, 2018, and July 1, 2020. We calculated a cumulative empiric antibiotic spectrum score by adapting a previously validated antibiotic spectrum index (ASI) and applying that score to empiric antibiotic use. We visualized these data as a heat map based on various day-of-week-time combinations and then compared the distribution of scores between weekday nights, weekend days, and weekend nights to the typical workweek hours (weekday days, weekday days) using the Mann-Whitney U nonparametric test with a Bonferroni correction. RESULTS: The analysis included 76,535 antibiotic starts across 53,900 unique patient admissions over 2 years. The mean cumulative ASI was higher in all 3 night and weekend combinations (weekday nights, 7.3; weekend days, 7.6; weekend nights, 7.5) compared to the weekday daytime hours (weekday days, 7.1) and the distribution of scores was different in all groups compared to the weekday daytime reference. The cumulative ASI was also higher in intensive care units. CONCLUSIONS: Empiric antibiotic prescribing patterns differed across space and time; broader antibiotic choices occurred in the intensive care units and on nights and weekends. Visualization of these patterns aids in antimicrobial prescribing pattern recognition and may assist in finding opportunities for additional antimicrobial stewardship interventions.

Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial.

BACKGROUND: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis. METHODS: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics. RESULTS: Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47-.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88-1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar. CONCLUSIONS: An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm. CLINICAL TRIALS REGISTRATION: NCT03517007.

Impact of COVID-19 pandemic on pharmacist-led allergy assessments and penicillin skin testing.

Allergy assessments and penicillin skin testing are associated with reductions in high-Clostridioides difficile infection (CDI)-risk antibiotic use and lower hospital-acquired CDI rates; however, these activities require substantial personnel and resource allocation. Recently, many antimicrobial stewardship programs' (ASPs) focus shifted towards supporting the COVID-19 pandemic response. We evaluated the impact of the COVID-19 pandemic on a pharmacist-led allergy assessment and penicillin skin testing program. Patients undergoing allergy assessment and/or penicillin skin testing (PST) from 1 January 2017 through 30 April 2021 were included for review. Monthly PST and allergy assessment rates were calculated and defined as the number of PSTs or allergy assessments per 1000 unique patient encounters for each month, respectively. The study used interrupted time series regression to assess potential level and slope changes in allergy assessments and PSTs during the pandemic. 200 058 total inpatient encounters by 188 867 unique patients occurred during the study period. ASP performed 918 allergy assessments and 204 PSTs. The local onset of the SARS-CoV-2 pandemic during March 2020 was associated with significant level reductions in allergy assessments and PSTs. Additional responsibilities added to the ASP team during the COVID-19 pandemic limited the ability to perform core antimicrobial stewardship activities with proven patient care benefits.

Impact of Education and Data Feedback on Guideline-Concordant Prescribing for Urinary Tract Infections in the Outpatient Setting.

BACKGROUND: Urinary tract infections (UTIs) are the most common outpatient indication for antibiotics and an important target for antimicrobial stewardship (AS) activities. With The Joint Commission standards now requiring outpatient AS, data supporting effective strategies are needed. METHODS: We conducted a 2-phase, prospective, quasi-experimental study to estimate the effect of an outpatient AS intervention on guideline-concordant antibiotic prescribing in a primary care (PC) clinic and an urgent care (UC) clinic between August 2017 and July 2019. Phase 1 of the intervention included the development of clinic-specific antibiograms and UTI diagnosis and treatment guidelines, presented during educational sessions with clinic providers. Phase 2, consisting of routine clinic- and provider-specific feedback, began ~12 months after the initial education. The primary outcome was percentage of encounters with first- or second-line antibiotics prescribed according to clinic-specific guidelines and was assessed using an interrupted time series approach. RESULTS: Data were collected on 4724 distinct patients seen during 6318 UTI encounters. The percentage of guideline-concordant prescribing increased by 22% (95% CI, 12% to 32%) after Phase 1 education, but decreased by 0.5% every 2 weeks afterwards (95% CI, -0.9% to 0%). Following routine data feedback in Phase 2, guideline concordance stabilized, and significant further decline was not seen (-0.6%; 95% CI, -1.6% to 0.4%). This shift in prescribing patterns resulted in a 52% decrease in fluoroquinolone use. CONCLUSIONS: Clinicians increased guideline-concordant prescribing, reduced UTI diagnoses, and limited use of high-collateral damage agents following this outpatient AS intervention. Routine data feedback was effective to maintain the response to the initial education.

Impact of Education and Data Feedback on Antibiotic Prescribing for Urinary Tract Infections in the Emergency Department: An Interrupted Time-Series Analysis.

BACKGROUND: Urinary tract infections (UTIs) are often misdiagnosed or treated with exceedingly broad-spectrum antibiotics, leading to negative downstream effects. We aimed to implement antimicrobial stewardship (AS) strategies targeting UTI prescribing in the emergency department (ED). METHODS: We conducted a quasi-experimental prospective AS intervention outlining appropriate UTI diagnosis and management across 3 EDs, within an academic and 2 community hospitals, in North Carolina, United States. The study was divided into 3 phases: a baseline period and 2 intervention phases. Phase 1 included introduction of an ED-specific urine antibiogram and UTI guideline, education, and department-specific feedback on UTI diagnosis and antibiotic prescribing. Phase 2 included re-education and provider-specific feedback. Eligible patients included adults with an antibiotic prescription for UTI diagnosed in the ED from 13 November 2018 to 1 March 2021. Admitted patients were excluded. The primary outcome was guideline-concordant antibiotic use, assessed using an interrupted time-series regression analysis with 2-week intervals. RESULTS: Overall, 8742 distinct patients with 10 426 patient encounters were included. Ninety-two percent of all encounters (n = 9583) were diagnosed with cystitis and 8.1% with pyelonephritis (n = 843). There was an initial 15% increase in guideline-concordant antibiotic prescribing in phase 1 compared with the preintervention period (incidence rate ratio [IRR], 1.15; 95% confidence interval [CI], 1.03-1.29). A significant increase in guideline-concordant prescriptions was seen with every 2-week interval during phase 2 (IRR, 1.03; 95% CI, 1.01-1.04). CONCLUSIONS: This multifaceted AS intervention involving a guideline, education, and provider-specific feedback increased guideline-concordant antibiotic choices for treat-and-release patients in the ED.

Impact of Antibiotic Stewardship Rounds in the Intensive Care Setting: A Prospective Cluster-Randomized Crossover Study.

BACKGROUND: Few groups have formally studied the effect of dedicated antibiotic stewardship rounds (ASRs) on antibiotic use (AU) in intensive care units (ICUs). METHODS: We implemented weekly ASRs using a 2-arm, cluster-randomized, crossover study in 5 ICUs at Duke University Hospital from November 2017 to June 2018. We excluded patients without an active antibiotic order, or if they had a marker of high complexity including an existing infectious disease consult, transplantation, ventricular assist device, or extracorporeal membrane oxygenation. AU during and following ICU stay for patients with ASRs was compared to the controls. We recorded the number of reviews, recommendations delivered, and responses. We evaluated change in ICU-specific AU during and after the study. RESULTS: Our analysis included 4683 patients: 2330 intervention and 2353 controls. Teams performed 761 reviews during ASRs, which excluded 1569 patients: 60% of patients off antibiotics, and 8% complex patients. Exclusions affected 88% of cardiothoracic ICU (CTICU) patients. The AU rate ratio (RR) was 0.97 (95% confidence interval [CI], .91-1.04). When CTICU was removed, the RR was 0.93 (95% CI, .89-.98). AU in the poststudy period decreased by 16% (95% CI, 11%-24%) compared to AU in the baseline period. Change in AU was differential among units: largest in the neurology ICU (-28%) and smallest in the CTICU (-2%). CONCLUSIONS: Weekly multidisciplinary ASRs was a high-resource intervention associated with a small AU reduction. The noticeable ICU AU decline over time is possibly due to indirect effects of ASRs. Effects differed among specialty ICUs, emphasizing the importance of customizing ASRs to match unit-specific population, workflow, and culture.

Sustained reduction in catheter-associated urinary tract infections using multi-faceted strategies led by champions: A quality improvement initiative.

We reviewed the sustainability of a multifaceted intervention on catheter-associated urinary tract infection (CAUTI) in 3 intensive care units. During the 4-year postintervention period, we observed reductions in urine culture rates (from 80.9 to 47.5 per 1,000 patient days; P < .01), catheter utilization (from 0.68 to 0.58; P < .01), and CAUTI incidence rates (from 1.7 to 0.8 per 1,000 patient days; P = .16).

Novel method of calculating adjusted antibiotic use by microbiological burden.

OBJECTIVE: To determine the usefulness of adjusting antibiotic use (AU) by prevalence of bacterial isolates as an alternative method for risk adjustment beyond hospital characteristics. DESIGN: Retrospective, observational, cross-sectional study. SETTING: Hospitals in the southeastern United States. METHODS: AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum ß-lactamase (ESBL)-producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal ß-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared. RESULTS: Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016. CONCLUSIONS: The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.

Antimicrobial Stewardship Practice in the Ambulatory Setting From a National Cohort.

BACKGROUND: The majority of antimicrobial use occurs in the ambulatory setting. Antimicrobial stewardship programs (ASPs) are effective in improving appropriate prescribing and are now required by accreditation bodies. METHODS: This was a cross-sectional, multicenter survey describing the current state of ambulatory ASPs in a national cohort of Vizient member hospitals with ambulatory healthcare settings and serves as a benchmark for stewardship strategies related to program effectiveness. RESULTS: One hundred twenty-nine survey responses from a variety of institution types across 44 states were received. Survey respondents reported a fully functioning ASP in 7% (9 of 129) of ambulatory practices compared with 88% (114 of 129) of inpatient institutions. Effectiveness in at least 1 antibiotic use-related outcome (ie, utilization, resistance, Clostridioides difficile infection, or cost) in the past 2 years was reported in 18% (18 of 100) of ambulatory and 84% (103 of 123) of inpatient ASPs. Characteristics of ambulatory ASPs demonstrating effectiveness were institution guidelines (89%, 16 of 18), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89% 16 of 18), outpatient antibiograms (78% 14 of 18), and dedicated pharmacist support (72%, 13 of 18). Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antimicrobial Stewardship (P < .001). CONCLUSIONS: Antimicrobial stewardship programs are needed in the ambulatory setting, but they are not common. Currently, few ambulatory ASPs in this survey self-identify as fully functioning. The CDC Core Elements of antimicrobial stewardship should remain foundational for ASP development and expansion.