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 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 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.

Evaluation of a Pharmacist-Led Penicillin Allergy Assessment Program and Allergy Delabeling in a Tertiary Care Hospital.

Importance: Penicillin allergies are frequently mislabeled, which may contribute to use of less-preferred alternative antibiotics. Objective: To evaluate a pharmacist-led allergy assessment program's association with antimicrobial use and clinical outcomes. Design, Setting, and Participants: A pharmacist-led allergy assessment program was launched in 2 phases (June 1, 2015, and November 2, 2016) at a single-center tertiary referral hospital. The longitudinal cross-sectional study included all study period adult admissions; hospitalwide outcomes were assessed by segmented regression. Individual outcomes were assessed within an embedded propensity score-matched case-control study of inpatients undergoing comprehensive allergy assessment following self-report of penicillin allergy. Analysis occurred from March 1, 2020, to February 29, 2020. Exposures: The longitudinal study analyzed hospital-level outcomes over 3 periods: preintervention (15 months), phase 1 (structured allergy history alone, 16 months), and phase 2 (comprehensive assessment including penicillin skin testing, 52 months). The case-control study defined cases as individuals undergoing comprehensive allergy assessment. Main Outcomes and Measures: Hospital-level outcomes included antibiotic days of therapy per 1000 patient-days and hospital-acquired Clostridioides difficile infection (CDI) incidence per 10 000 patient-days. Individual outcomes included antibiotic selection, overall survival, and CDI-free survival. Results: Longitudinal analysis spanned 2014-2020 (median admissions, 46 416 per year; interquartile range [IQR], 46 001-50 091 per year). Hospitalwide, allergy histories were temporally associated with decreased use of nonpenicillin alternative antibiotics (rate ratio, 0.87; 95% CI, 0.79-0.97) and high-CDI-risk antibiotics (rate ratio, 0.91; 95% CI, 0.85-0.98). Penicillin skin testing was temporally associated with lower hospital-acquired CDI rates (rate ratio, 0.61; 95% CI, 0.43-0.86). The embedded case-control study included 272 cases and 819 controls. Median age was 63 years (interquartile range, 51-73 years), 553 (50.7%) patients were women, and 229 (21.0%) patients were Black. Allergy-assessed patients were less likely to receive high-CDI-risk antibiotics at discharge (odds ratio, 0.66; 95% CI, 0.44-0.98). Estimated reductions in mortality (hazard ratio, 0.77; 95% CI, 0.55-1.07) and hospital-acquired CDI risk (hazard ratio, 0.53; 95% CI, 0.18-1.55) were not statistically significant. Conclusions and Relevance: Pharmacist-led allergy assessments may be associated with reduced high-CDI-risk antibiotic use at both hospitalwide and individual levels. Although individual reductions in mortality and CDI risk did not achieve significance, divergence of survival curves suggest longer-term benefits of allergy delabeling warrant future study.

Total duration of antimicrobial therapy resulting from inpatient hospitalization.

OBJECTIVE: To assess the feasibility of electronic data capture of postdischarge durations and evaluate total durations of antimicrobial exposure related to inpatient hospital stays. DESIGN: Multicenter, retrospective cohort study. SETTING: Two community hospitals and 1 academic medical center. PATIENTS: Hospitalized patients who received ≥1 dose of a systemic antimicrobial agent. METHODS: We collected and reviewed electronic data on inpatient and discharge antimicrobial prescribing from April to September 2016 in 3 pilot hospitals. Inpatient antimicrobial use was obtained from electronic medication administration records. Postdischarge antimicrobial use was calculated from electronic discharge prescriptions. We completed a manual validation to evaluate the ability of electronic prescriptions to capture intended postdischarge antibiotics. Inpatient, postdischarge, and total lengths of therapy (LOT) per admission were calculated to assess durations of antimicrobial therapy attributed to hospitalization. RESULTS: A total of 45,693 inpatient admissions were evaluated. Antimicrobials were given during 23,447 admissions (51%), and electronic discharge prescriptions were captured in 7,442 admissions (16%). Manual validation revealed incomplete data capture in scenarios in which prescribers avoided the electronic system. The postdischarge LOT among admissions with discharge antimicrobials was median 8 days (range, 1-360) with peaks at 5, 7, 10, and 14 days. Postdischarge days accounted for 38% of antimicrobial exposure days. CONCLUSION: Discharge antimicrobial therapy accounted for a large portion of antimicrobial exposure related to inpatient hospital stays. Discharge prescription data can feasibly be captured through electronic prescribing records and may aid in designing stewardship interventions at transitions of care.

Effectiveness of Vancomycin or Beta-Lactam Therapy in Ampicillin-Susceptible Enterococcus spp. Bloodstream Infections.

BACKGROUND: De-escalation to a beta-lactam improves outcomes for patients with a methicillin-susceptible Staphylococcus aureus bloodstream infection (BSI). Whether a similar strategy is appropriate for enterococcal species is less clear. OBJECTIVE: To determine whether definitive antibiotic selection affects outcomes for patients with an ampicillin-susceptible enterococcal BSI. METHODS: This retrospective cohort study included patients over 18 years of age receiving definitive therapy with vancomycin or a beta-lactam for one or more blood cultures positive for Enterococcus spp. isolates between 2007 and 2014. Survival differences were examined using a Kaplan-Meier curve with log-rank test. RESULTS: One-hundred eighty-six patients received definitive therapy with either vancomycin (n = 45, 24.2%) or a beta-lactam (n = 141, 75.8%). The primary outcome, 30-day all-cause mortality, was not different between groups (6.7% vs 7.1%; P = .992). A post hoc analysis of all-cause mortality 1 year after the index BSI was significantly higher in the vancomycin group (51% vs 33%; P = .032). In a Cox proportional hazards regression model, definitive vancomycin was associated with an increased risk of all-cause mortality at 1 year (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.41-4.04). CONCLUSION: For patients with an ampicillin-susceptible enterococcal BSI, definitive therapy with vancomycin or a beta-lactam was not independently associated with a difference in 30-day all-cause mortality. Whether definitive vancomycin is associated with poor long-term outcomes warrants further exploration.

Influence of Reported Penicillin Allergy on Mortality in MSSA Bacteremia.

BACKGROUND: Penicillin allergy frequently impacts antibiotic choice. As beta-lactams are superior to vancomycin in treating methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, we examined the effect of reported penicillin allergy on clinical outcomes in patients with MSSA bacteremia. METHODS: In this retrospective cohort study of adults with MSSA bacteremia admitted to a large tertiary care hospital, outcomes were examined according to reported penicillin allergy. Primary outcomes included 30-day and 90-day mortality rates. Multivariable regression models were developed to quantify the effect of reported penicillin allergy on mortality while adjusting for potential confounders. RESULTS: From 2010 to 2015, 318 patients with MSSA bacteremia were identified. Reported penicillin allergy had no significant effect on adjusted 30-day mortality (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.29-1.84; P = .51). Patients with reported penicillin allergy were more likely to receive vancomycin (38% vs 11%, P < .01), but a large number received cefazolin regardless of reported allergy (29 of 66, 44%). Mortality rates were highest among nonallergic patients receiving vancomycin (22.6% vs 7.4% for those receiving beta-lactams regardless of reported allergy, P < .01). In multivariable analysis, beta-lactam receipt was most strongly associated with survival (OR, 0.26; 95% CI, 0.12-0.54). CONCLUSIONS: Reported penicillin allergy had no significant effect on 30- or 90-day mortality. Non-penicillin-allergic patients receiving vancomycin for treatment of MSSA bacteremia had the highest mortality rates overall. Receipt of a beta-lactam was the strongest predictor of survival. These results underscore the importance of correct classification of patients with penicillin allergy and appropriate treatment with a beta-lactam when tolerated.

Impact of automatic infectious diseases consultation on the management of fungemia at a large academic medical center.

PURPOSE: The impact of automatic infectious diseases (ID) consultation for inpatients with fungemia at a large academic medical center was studied. METHODS: In this single-center, retrospective study, the time to appropriate antifungal therapy before and after implementing a policy requiring automatic ID consultation for the management of fungemia for all patients with an inpatient positive blood culture for fungus was examined. The rates of ID consultation; the likelihood of receiving appropriate antifungal therapy; central venous catheter (CVC) removal rates; performance of ophthalmologic examinations; infection-related length of stay (LOS); rates of all-cause inhospital mortality, death, or transfer to an intensive care unit within 7 days of first culture; and inpatient cost of antifungals were also evaluated. RESULTS: A total of 173 unique episodes (94 and 79 in the control and intervention groups, respectively) were included. Candida species were the most frequently cultured organisms, isolated from over 90% of patients in both groups. No differences were observed between the control and intervention groups in time to appropriate therapy, infection-related LOS, or time to CVC removal. However, patients in the intervention group were more likely than those in the control group to receive appropriate antifungal therapy (p = 0.0392), undergo ophthalmologic examination (p = 0.003), have their CVC removed (p = 0.0038), and receive ID consultation (p = 0.0123). Inpatient antifungal costs were significantly higher in the intervention group (p = 0.0177). CONCLUSION: While automatic ID consultation for inpatients with fungemia did not affect the time to administration of appropriate therapy, improvement was observed for several process indicators, including rates of appropriate antifungal therapy selection, time to removal of CVCs, and performance of ophthalmologic examinations.