Virk, Abinash

Abstract Objective This study aimed to conduct a scoping review of machine learning (ML) techniques in outpatient parenteral antimicrobial therapy (OPAT) for predicting adverse outcomes and to evaluate their validation, implementation and potential barriers to adoption. Materials and methods This scoping review included studies applying ML algorithms to adult OPAT patients, covering techniques from logistic regression to neural networks. Outcomes considered were medication intolerance, toxicity, catheter complications, hospital readmission and patient deterioration. A comprehensive search was conducted across databases including Cochrane Central, Cochrane Reviews, Embase, Ovid MEDLINE and Scopus, from 1 January 2000 to 1 January 2024. Results Thirty-two studies met the inclusion criteria, with the majority being single-centre experiences primarily from North America. Most studies focused on developing new ML models to predict outcomes such as hospital readmissions and medication-related complications. However, there was very little reporting on the performance characteristics of these models, such as specificity, sensitivity and C-statistics. There was a lack of multi-centre or cross-centre validation, limiting generalizability. Few studies advanced beyond traditional logistic regression models, and integration into clinical practice remains limited. Discussion ML shows promise for enhancing OPAT outcomes by predicting adverse events and enabling pre-emptive interventions. Despite this potential, significant gaps exist in development, validation and practical implementation. Barriers include the need for representative data sets and broadly applicable, validated models. Conclusion Future research should address these barriers to fully leverage ML’s potential in optimizing OPAT care and patient safety. Models must deliver timely, accurate and actionable insights to improve adverse event prediction and prevention in OPAT settings.

Abstract Background Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent postacute sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies based on symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings. Methods In this retrospective cohort of patients with an initial SARS-CoV-2 infection who were continually empaneled for primary care in a large US health system, the electronic health record was queried for preinfection vaccination status, demographics, comorbidity index, and diagnosed conditions. Multivariable logistic regression was used to model the outcome of a medically attended PASC diagnosis within 6 months of SARS-CoV-2 infection. Likelihood ratio tests were used to assess the interaction between vaccination status and prevalent variant at the time of infection and between vaccination status and hospitalization for SARS-CoV-2 infection. Results During the observation period, 6.9% of patients experienced medically attended and diagnosed PASC. A diagnosis of PASC was associated with older age, female sex, hospitalization for the initial infection, and an increased severity-weighted comorbidity index and was inversely associated with infection during the Omicron period. No difference in the development of diagnosed PASC was observed between unvaccinated patients and those vaccinated with either 2 doses of an mRNA vaccine or >2 doses. Conclusions We found no association between vaccination status at the time of infection and development of medically diagnosed PASC. Vaccine remains an important measure to prevent SARS-CoV-2 infection and severity. Further research is needed to identify effective measures to prevent and treat PASC.

Abstract Background Post-discharge culture and susceptibility review has been described in emergency department and urgent care settings, but there is a lack of published literature describing culture review after acute care hospitalizations. Awaiting microbiology results can impede timely patient discharge. However, discharging patients while microbiology results are pending may result in suboptimal therapy or lost opportunity for additional testing/follow up. We implemented an antimicrobial stewardship effort to identify microbiology tests that result post-discharge utilizing a custom report in the electronic medical record (EMR). Methods. This retrospective descriptive study included adult patients ( >18 years of age) at 4 sites within Mayo Clinic from 1/1/2019 to 2/28/2023. Eligible patients had a hospitalization with an ID consult and an abnormal culture that was reviewed by an antimicrobial stewardship pharmacist after discharge. Urine cultures were excluded. The details of pharmacist-initiated antimicrobial stewardship interventions based on the culture review were identified by an EMR based research report. Results A total of 6803 patient encounters with at least 1 microbiology result reviewed post-discharge were identified. Patients were 40% female with a median age of 62 years. Patient race was 89.8% white, 4% black/African American, 1.5% Asian, and < 1% other. Of these patients, 1983 (29%) had at least one pharmacist intervention. A total of 169 (2.5%) of these patients had multiple interventions. Interventions included modification of antimicrobial therapy, addition of susceptibility testing, or additional follow up (labs, imaging, or patient visits). Median time from culture update to pharmacist review was 27.2 hours. Median length of hospital stay was 5 days and discharge disposition was home with self care (65%), home with home health or hospice (22.7%), or discharge to another acute care or skilled nursing facility (12.3%). Conclusion Outpatient review of post-discharge culture updates utilizing EMR reporting led to substantial interventions impacting antimicrobial treatments. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria

Abstract Background Optimizing antimicrobial regimens for outpatients with community-acquired pneumonia (CAP) represents an area of opportunity for ambulatory antimicrobial stewardship programs. A pre-populated, antibiotic order panel for outpatient respiratory syndromes was implemented in the Mayo Clinic Enterprise on 1/4/2021. For CAP, it provides national guideline adherent regimens (i.e., selection, dosing, and durations) by patient comorbidity and beta-lactam allergy status. We aimed to assess impacts of panel use on antibiotic prescribing in outpatients with CAP. Methods This retrospective review included Mayo Clinic outpatient encounters from Minnesota in 2021 and 2022. Eligible encounters used a CAP-related primary ICD-10 code, conveyed intention to treat CAP in encounter notes, and were performed by primary care, emergency department, or urgent care clinicians who managed ≥1 CAP patient with the panel and ≥1 without the panel during the study period. Encounters were excluded if patients were already receiving antibiotics at the time of encounter. The primary outcome was adherence (drug and duration) to guideline recommendations. Secondary outcomes included utilization rate by agent and therapy duration. Outcomes were analyzed with Kruskal-Wallis rank sum and Pearson’s chi-squared tests (α level = 0.05). Results 352 encounters (134 panel vs. 218 non-panel) were included. Prescribing was guideline adherent in 61.9% and 29.4% (p< 0.01) of panel and non-panel encounters, respectively. The most common reason for guideline non-adherence during panel use was inappropriate drug selection (n = 45/51, 88.2%). This was predominantly driven by use of the incorrect section of the treatment panel based on patient comorbidity status (n = 30/45, 66.7%). Individual antibiotic utilization rates differed between panel and non-panel cohorts (Table 1), with higher rates of amoxicillin and amoxicillin/clavulanate use and lower rates of azithromycin and doxycycline use in the panel cohort. Durations >5 days were more common in the non-panel as compared to the panel cohort (34.4% vs. 7.5%, p < 0.01). Conclusion Use of a pre-populated antimicrobial order panel in outpatients with CAP resulted in greater adherence to national guideline recommendations. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun: Grant/Research Support|Cidara: Grant/Research Support|Scynexis: Grant/Research Support

Abstract Background The aim of this study was to evaluate the frequency of unnecessary antibiotic prescribing for Tier 3 upper respiratory infection (URI) syndromes across the Mayo Clinic Enterprise before and after a multifaceted antimicrobial stewardship intervention, and to determine ongoing factors associated with antibiotic prescribing and repeat respiratory healthcare contact in the postintervention period. Methods This was a quasi-experimental, pre/post, retrospective cohort study from 1 January 2019 through 31 December 2022, with 12-month washout during implementation from 1 July 2020 through 30 June 2021. All outpatient encounters, adult and pediatric, from primary care, urgent care, and emergency medicine specialties with a Tier 3 URI diagnosis were included. The intervention was a multifaceted outpatient antibiotic stewardship bundle. The primary outcome was the rate of antibiotic prescribing in Tier 3 encounters. Secondary outcomes included 14-day repeat healthcare contact for respiratory indications and factors associated with persistent unnecessary prescribing. Results A total of 165 658 Tier 3 encounters, 96 125 in the preintervention and 69 533 in the postintervention period, were included. Following intervention, the prescribing rate for Tier 3 encounters decreased from 21.7% to 11.2% (P < .001). Repeat 14-day respiratory healthcare contact in the no antibiotic group was lower postintervention (9.9.% vs 9.4%; P = .004). Multivariable models indicated that increasing patient age, Charlson comorbidity index, and primary diagnosis selected were the most important factors associated with persistent unnecessary antibiotic prescribing. Conclusions Outpatient antibiotic stewardship initiatives can reduce unnecessary antibiotic prescribing for Tier 3 URIs without increasing repeat respiratory healthcare contact. Advancing age and number of comorbidities remain risk factors for persistent unnecessary antibiotic prescribing.

Abstract Purpose Mayer's theory of multimedia learning proposes that personalisation and embodiment (P/E) can improve outcomes in e‐Learning. The authors hypothesised that an e‐Learning module enhanced by P/E principles would lead to higher knowledge, perceived P/E and motivation among health care professionals, compared with an unenhanced module. Methods The authors conducted a randomised trial comparing two versions of a 30‐minute multimedia e‐Learning module addressing the antibiotic management of pneumonia. The unenhanced format used slides with voiceover (human voice but no visible speaker), formal language and no specific P/E strategies. The enhanced format additionally implemented P/E strategies including conversational style, polite language, visible author, social congruence, human‐like presence and professional presence by subtly changing the script and substituting several short videos of subject matter experts. Participants included pharmacists, physicians and advanced practice providers from three academic and several community hospitals. Outcomes included knowledge, perceived P/E (assessed by the Congruence Personalisation Questionnaire, CPQ), motivation (assessed via the Instructional Materials Motivation Survey [IMMS] and Motivated Strategies for Learning Questionnaire [MSLQ]) and course satisfaction. Results There were 406 participants including 225 pharmacists, 109 physicians and 72 advanced practice providers. Post‐module knowledge was slightly higher for the enhanced versus the unenhanced format, but the difference did not reach statistical significance (adjusted mean difference, 0.04 of 10 possible, [95% CI −0.26, 0.34], p = 0.78; Cohen d 0.02). Participant perceptions of P/E (measured via CPQ) were significantly greater for the enhanced format (difference 0.46 of 5 possible [0.35, 0.56], p < 0.001; Cohen d 0.85), as were motivational features of the e‐Learning course (measured via IMMS) (difference 0.14 of 5 possible [0.02, 0.26], p = 0.02; Cohen d 0.24). Participants' overall motivational orientation (measured via MSLQ) and course satisfaction were not significantly different between the two formats ( p > 0.05). Conclusion Application of P/E principles to an e‐Learning module led to greater perceived P/E and motivational features but did not influence knowledge.

Background: Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin–tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed. Results: AKI occurred in 14.4% of patients in the VPT group ( n = 15/104) compared to 5.5% in the other BL group ( n = 40/722) ( p < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7–12.0) days in the VPT group and 10.9 (5–22.7) days in the other BL group ( p = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33–4.65), p = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group ( n = 15/104) and 5.3% in the other BL group ( n = 11/208) ( p = 0.006). Receipt of VPT [HR: 2.55 (1.36–4.78), p = 0.004] and acyclovir [HR: 2.38 (1.19–4.74), p = 0.014) remained significantly associated with AKI in the multivariable model. Conclusion: Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.

Abstract Background The protective efficacy of prior coronavirus disease 2019 (COVID-19) with or without vaccination remains unknown. This study sought to understand if 2 or more messenger RNA (mRNA) vaccine doses provide additional protection in patients with prior infection, or if infection alone provides comparable protection. Methods We conducted a retrospective cohort study of the risk of COVID-19 from 16 December 2020 through 15 March 2022, among vaccinated and unvaccinated patients of all ages with and without prior infection. A Simon-Makuch hazard plot illustrated the incidence of COVID-19 between groups. Multivariable Cox proportional hazards regression was used to examine the association of demographics, prior infection, and vaccination status with new infection. Results Among 101 941 individuals with at least 1 COVID-19 polymerase chain reaction test prior to 15 March 2022, 72 361 (71.0%) received mRNA vaccination and 5957 (5.8%) were previously infected. The cumulative incidence of COVID-19 was substantially higher throughout the study period for those previously uninfected and unvaccinated, and lowest for those previously infected and vaccinated. After accounting for age, sex, and the interaction between vaccination and prior infection, a reduction in reinfection risk was noted during the Omicron and pre-Omicron phases of 26% (95% confidence interval [CI], 8%–41%; P = .0065) to 36% (95% CI, 10%–54%; P = .0108), respectively, among previously infected and vaccinated individuals, compared to previously infected subjects without vaccination. Conclusions Vaccination was associated with lower risk of COVID-19, including in those with prior infection. Vaccination should be encouraged for all including those with prior infection, especially as new variants emerge and variant-specific booster vaccines become available.