Virk, Abinash

Abstract Background URIs are the most common indication for outpatient antibiotic prescribing. Given high rates of unnecessary prescribing, these indications have been identified as a high-priority target for outpatient antimicrobial stewardship programs (ASP). Our primary objective was to evaluate the impact of a system-wide, multifaceted, outpatient ASP intervention bundle on unnecessary antibiotic prescribing for URI. Methods This quasi-experimental study was conducted from 2019 to 2021. ICD-10 codes for URIs were grouped into 3 tiers (i.e., tier I = antibiotics always indicated, tier II = sometimes, tier III = never). Encounters from 5 care specialties (i.e., family medicine, community internal medicine, express care, pediatrics, and emergency department) with a tier III URI primary ICD-10 code but without a secondary tier I or tier II code were included. COVID-19 ICD-10 codes were excluded. Interventions included construction of a prescribing data model, dissemination of clinician prescribing data and education, promotion of symptom management strategies, a patient-facing commitment poster, and a pre-populated URI order panel. Tools were designed at a system level and implemented by regional champions beginning in the 3rd quarter of 2020. The primary outcome was the rate of antibiotic prescribing, and the secondary outcome and counterbalance measure was the rate of repeat URI-related healthcare contact within 14 days. Outcomes were analyzed with chi-square with an α level of 0.05. Results A total of 147403 encounters were included. The overall antibiotic prescribing rate decreased from 24.1% to 12.3% between 2019 and 2021 (p< 0.01). Significant reductions in tier III antibiotic prescribing were demonstrated for each region, care specialty, and syndrome evaluated (Table 1). A reduction in repeat healthcare contact was seen across the total cohort (9.5% in 2019 vs. 8.3% in 2021, p< 0.01); decreases in repeat contact rates were observed in those not initially receiving an antibiotic (10.3% vs. 8.6%, p< 0.01), but not in those who initially received an antibiotic (6.8% vs. 6.8%, p = 0.94). Tier III URI encounter level antimicrobial prescribing rates by region, care specialty, and syndrome Conclusion A multifaceted, outpatient ASP intervention bundle decreased rates of unnecessary antimicrobial prescribing without increasing rates of 14-day repeat URI-related healthcare contact. Disclosures Paschalis Vergidis, MD, AbbVie: DSMB|Cidara: Grant/Research Support|Scynexis: Grant/Research Support Evan Draper, PharmD, Gilead Foundation: Grant/Research Support Sara Ausman, PharmD, Gilead: Honoraria Christina G. Rivera, PharmD, Gilead: Grant/Research Support|Gilead: Honoraria|Insmed: Honoraria.

Abstract Background Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD. Methods This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response. Results The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR. Conclusions Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

The precision health era is likely to reduce and respond to antimicrobial resistance (AMR). Our stewardship and precision efforts share terminology, seeking to deliver the “right drug, at the right dose, at the right time.” Already, rapid diagnostic testing, phylogenetic surveillance, and real-time outbreak response provide just a few examples of molecular advances we dub “precision stewardship.” However, the AMR causal factors range from the molecular to that of global health policy. Mirroring the cross-sectoral nature of AMR science, the research addressing the ethical, legal and social implications (ELSI) of AMR ranges across academic scholarship. As the rise of AMR is accompanied by an escalating sense of its moral and social significance, what is needed is a parallel field of study. In this paper, we offer a gap analysis of this terrain, or an agenda for “the ELSI of precision stewardship.” In the first section, we discuss the accomplishments of a multi-decade U.S. national investment in ELSI research attending to the advances in human genetics. In the next section, we provide an overview of distinct ELSI topics pertinent to AMR. The distinctiveness of an ELSI agenda for precision stewardship suggests new opportunities for collaboration to build the stewardship teams of the future.

Abstract COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2 against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice from January 2021 through January 2022. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. There were 5,985 symptomatic individuals with a positive test after full vaccination with BNT162b2 (cases) and 32,728 negative tests contributed by 27,753 symptomatic individuals after full vaccination (controls). The adjusted odds of symptomatic infection were higher 250 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.62, 95% CI: 2.52 to 5.20). The odds of infection were still lower 285 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.50, 95% CI: 0.37 to 0.67), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of non-COVID-19 associated hospitalization (negative control) decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. In summary, BNT162b2 strongly protected against symptomatic SARS-CoV-2 infection for at least 8 months after full vaccination, but the degree of protection waned significantly over this period.

Abstract COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection against symptomatic infection after vaccination with mRNA-1273. We fit conditional logistic regression (CLR) models stratified on residential county and calendar date of SARS-CoV-2 PCR testing to assess the association between the time elapsed since vaccination and the odds of symptomatic infection, adjusted for several covariates. There were 2,364 symptomatic individuals who had a positive SARS-CoV-2 PCR test after full vaccination with mRNA-1273 (“cases”) and 12,949 symptomatic individuals who contributed 15,087 negative tests after full vaccination (“controls”). The odds of symptomatic infection were significantly higher 250 days after full vaccination compared to the date of full vaccination (Odds Ratio [OR]: 2.47, 95% confidence interval [CI]: 1.19–5.13). The odds of non-COVID-19 associated hospitalization and non-COVID-19 pneumonia (negative control outcomes) remained relatively stable over the same time interval (Day 250 ORNon-COVID Hospitalization: 0.68, 95% CI: 0.47–1.0; Day 250 ORNon-COVID Pneumonia: 1.11, 95% CI: 0.24–5.2). The odds of symptomatic infection remained significantly lower almost 300 days after the first mRNA-1273 dose as compared to 4 days after the first dose, when immune protection approximates the unvaccinated state (OR: 0.26, 95% CI: 0.17–0.39). Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. In summary, mRNA-1273 robustly protected against symptomatic SARS-CoV-2 infection at least 8 months after full vaccination, but the degree of protection waned over this time period.

Abstract As of 2021 November 29, booster vaccination against SARS-CoV-2 infection has been recommended for all individuals aged 18 years and older in the United States. A key reason for this recommendation is the expectation that a booster vaccine dose can alleviate observed waning of vaccine effectiveness (VE). Although initial reports of booster effectiveness have been positive, the level of protection from booster vaccination is unclear. We conducted two studies to assess the impact of booster vaccination, with BNT162b2 or mRNA-1273, on the incidence of SARS-CoV-2 infection between August and December 2021. We first compared SARS-CoV-2 infection incidence in cohorts of 3-dose vaccine recipients to incidence in matched cohorts of 2-dose vaccine recipients (cohort size = 24,539 for BNT162b2 and 14,004 for mRNA-1273). Additionally, we applied a test-negative study design to compare the level of protection against symptomatic infection in 3-dose recipients to that observed in recent 2-dose primary vaccine series recipients. The 3-dose recipients experienced a significantly lower incidence rate of SARS-CoV-2 infection than the matched 2-dose cohorts (BNT162b2 Incidence Rate Ratio: 0.11, 95% CI: 0.09 to 0.13 and mRNA-1273 IRR: 0.11, 95% CI: 0.08 to 0.15). Results from the test-negative study showed the third vaccine dose mitigated waning of VE, with the risk of symptomatic infection in 3-dose recipients being comparable to that observed 7 to 73 days after the primary vaccine series. These results show that 3-dose vaccine regimens with BNT162b2 or mRNA-1273 are effective at reducing SARS-CoV-2 infection and support the widespread administration of booster vaccine doses.

Abstract Background Myocarditis following coronavirus disease 2019 (COVID-19) mRNA vaccines (Pfizer-BioNTech and Moderna) has been increasingly reported. Incidence rates in the general population are lacking, with pericarditis rather than myocarditis diagnostic codes being used to estimate background rates. This comparison is critical for balancing the risk of vaccination with the risk of no vaccination. Methods A retrospective case series was performed using the Mayo Clinic COVID-19 Vaccine Registry. We measured the incidence rate ratio (IRR) for myocarditis temporally related to COVID-19 mRNA vaccination compared with myocarditis in a comparable population from 2016 through 2020. Clinical characteristics and outcomes of the affected patients were collected. A total of 21 individuals were identified, but ultimately 7 patients met the inclusion criteria for vaccine-associated myocarditis. Results The overall IRR of COVID-19–related myocarditis was 4.18 (95% confidence interval [CI], 1.63–8.98), which was entirely attributable to an increased IRR among adult males (IRR, 6.69; 95% CI, 2.35–15.52) compared with females (IRR 1.41; 95% CI, .03–8.45). All cases occurred within 2 weeks of a dose of the COVID-19 mRNA vaccine, with the majority occurring within 3 days (range, 1–13) following the second dose (6 of 7 patients, 86%). Overall, cases were mild, and all patients survived. Conclusions Myocarditis is a rare adverse event associated with COVID-19 mRNA vaccines. It occurs in adult males with significantly higher incidence than in the background population. Recurrence of myocarditis after a subsequent mRNA vaccine dose is not known at this time.

AbstractHuman antimicrobial consumption largely occurs in the ambulatory setting, with inappropriate or unnecessary antimicrobial prescribing well documented in the literature. In 2020, The Joint Commission implemented a regulatory standard requiring the development and implementation of antimicrobial stewardship programs (ASP) in those institutions surveyed under the ambulatory accreditation standard. While experience with inpatient antimicrobial stewardship has continued to increase, ambulatory ASPs are programmatically distinct and can present unique challenges with regards to operationalizing regulatory components. Herein, we lay a framework for addressing the task of developing an ambulatory ASP for a large health system by reviewing the regulatory requirements, examining relevant recent publications, and describing our institutional experience.