IMPORTANCE: The natural history of C. difficile progression in nucleic acid amplification test (NAAT) positive, toxin enzyme immunoassay-negative patients remains poorly described. Better understanding risk for subsequent disease may improve prevention strategies. OBJECTIVE: Describe the natural history of C. difficile NAAT+/toxin- adults. DESIGN: A cohort of adults (≥18 years) tested for C. difficile within Duke University Health System between 15 March 2020 and 31 December 2023 were classified as NAAT-, NAAT+/toxin-, or NAAT+/toxin+ and followed up to 90 days. Three time-to-event analyses were conducted. Incidence of toxin+ episodes was assessed by initial test status (analysis 1). Treatment of NAAT+/toxin- adults was described using cumulative incidence curves (analysis 2). Rates of toxin+ episodes and severe disease were compared between treated and untreated NAAT+/toxin- adults (analysis 3). RESULTS: The cohort included 24,474 tests and 440 toxin+ episodes among 18,337 unique subjects followed for a median 71 days. NAAT+/toxin- status was associated with subsequent toxin positivity (adjusted hazard ratio, aHR 5.06, 95% CI 3.61-7.10) - especially after antibiotic receipt (aHR 15.71, 95% CI 9.85-25.06). Among 2,334 NAAT+/toxin- episodes, 33% received presumptive treatment. Just 5% of NAAT+/toxin- subjects progressed to toxin positivity. Presumptive treatment was associated with lower hazard of subsequent toxin positivity (aHR 0.12, 95% CI 0.05-0.29) but not fulminant disease (aHR 1.93, 95% CI 0.50-7.45). CONCLUSIONS AND RELEVANCE: C. difficile NAAT+/toxin- status was associated with subsequent toxin positivity, especially after antibiotic receipt, though absolute risk was low overall. Further research is needed to determine whether and for whom presumptive treatment might be beneficial.

Shifts in colorectal cancer (CRC) screening, including guidance from the United States Preventive Services Task Force lowering the recommended screening age from 50 to 45 years in 2021, may leave gaps in clinicians' understanding of related barriers and beliefs held by patients. This study uses the National Institute on Minority Health and Health Disparities Research Framework to analyze factors influencing CRC screening uptake among individuals aged 44-54 years and identifies how gaps in knowledge intersect with screening barriers, particularly as they relate to the health care system and sociocultural environment. In 2022, the Centers for Disease Control and Prevention's Division of Cancer Prevention and Control's Screen for Life campaign conducted 12 online focus groups to gather audience insights and test materials. Researchers conducted the focus groups in English and Spanish with individuals aged 44-54 years who had never had CRC and had never received a CRC screening. Focus groups gauged participants' knowledge, awareness, and behavior pertaining to CRC and CRC screening. Results show that participants often lacked knowledge about risk factors and screening modalities and appreciated emotionally resonant communication approaches that addressed gaps in knowledge using demystifying, destigmatizing language and representative imagery. Findings also indicate a need to help patients overcome barriers related to insurance coverage, treatment options, and discrimination. Results may guide the development of future health promotion efforts and empower health care providers to approach conversations with their patients with additional context regarding patients' needs.

BACKGROUND: Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown. METHODS: We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion. RESULTS: After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection. CONCLUSIONS: The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial.

BACKGROUND: Antimicrobial stewardship programs (ASPs) promote the principle of de-escalation: moving from broad to narrow spectrum agents and stopping antibiotics when no longer indicated. A standard, objective definition of de-escalation applied to electronic data could be useful for ASP assessments. METHODS: We derived an electronic definition of antibiotic de-escalation and performed a retrospective study among five hospitals. Antibiotics were ranked into 4 categories: narrow spectrum, broad spectrum, extended spectrum, and agents targeted for protection. Eligible adult patients were cared for on inpatient units, had antibiotic therapy for at least 2 days, and were hospitalized for at least 3 days after starting antibiotics. Number of antibiotics and rank were assessed at two time points: day of antibiotic initiation and either day of discharge or day 5. De-escalation was defined as reduction in either the number of antibiotics or rank. Escalation was an increase in either number or rank. Unchanged was either no change or discordant directions of change. We summarized outcomes among hospitals, units, and diagnoses. RESULTS: Among 39,226 eligible admissions, de-escalation occurred in 14,138 (36%), escalation in 5,129 (13%), and antibiotics were unchanged in 19,959 (51%). De-escalation varied among hospitals (median 37%, range 31-39%, p<.001). Diagnoses with lower de-escalation rates included intra-abdominal (23%) and skin and soft tissue (28%) infections. Critical care had higher rates of both de-escalation and escalation compared with wards. CONCLUSIONS: Our electronic de-escalation metric demonstrated variation among hospitals, units, and diagnoses. This metric may be useful for assessing stewardship opportunities and impact.

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.

Antimicrobial stewardship programs (ASPs) positively impact patient care, but metrics to assess ASP impact are poorly defined. We used a modified Delphi approach to select relevant metrics for assessing patient-level interventions in acute care settings for the purposes of internal program decision-making. An expert panel rated 90 candidate metrics on a 9-point Likert scale for association with four criteria: improved antimicrobial prescribing, improved patient care, utility in targeting stewardship efforts, and feasibility in hospitals with electronic health records. Experts further refined, added, or removed metrics during structured teleconferences and re-rated the retained metrics. Six metrics were rated >6 in all criteria: two measures of Clostridium difficile incidence, incidence of drug-resistant pathogens, days of therapy over admissions, days of therapy over patient days, and redundant therapy events. Fourteen metrics rated >6 in all criteria except feasibility were identified as targets for future development.

Antimicrobial stewardship is pivotal to improving patient outcomes, reducing adverse events, decreasing healthcare costs, and preventing further emergence of antimicrobial resistance. In an era in which antimicrobial resistance is increasing, judicious antimicrobial use is the responsibility of every healthcare provider. While antimicrobial stewardship programs (ASPs) have made headway in improving antimicrobial prescribing using such "top-down" methods as formulary restriction and prospective audit with feedback, engagement of prescribers has not been fully explored. Strategies that include frontline prescribers and other unit-based healthcare providers have the potential to expand stewardship, both to augment existing centralized ASPs and to provide alternative approaches to perform stewardship at healthcare facilities with limited resources. This review discusses interventions focusing on antimicrobial prescribing at the point of prescription as well as a pilot project to engage unit-based healthcare providers in antimicrobial stewardship.