O’Horo, John C.

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 Antispike monoclonal antibody treatment of 180 B-cell-depleted patients with mild-to-moderate coronavirus disease 2019 (COVID-19) resulted in good outcomes overall, with only 12.2% progressing to severe disease, 9.4% requiring hospitalization, 0.6% requiring mechanical ventilation, no deaths within 30 days, and 1.8% developing persistent COVID-19. Antispike monoclonal antibodies appear effective in this immunocompromised population.

Objective: To evaluate the performance of an Electronic Health Record (EHR) integrated risk score for COVID-19 positive outpatients to predict 30-day risk of hospitalization. Patients and Methods: A retrospective observational study of 67 470 patients with COVID-19 confirmed by polymerase chain reaction (PCR) test between March 12, 2020 and February 8, 2021. Risk scores were calculated based on data in the chart at the time of the incident infection. Results: The Mayo Clinic COVID-19 risk score consisted of 13 components included age, sex, chronic lung disease, congenital heart disease, congestive heart failure, coronary artery disease, diabetes mellitus, end stage liver disease, end stage renal disease, hypertension, immune compromised, nursing home resident, and pregnant. Univariate analysis showed all components, except pregnancy, have significant ( P < .001) association with admission. The Mayo Clinic COVID-19 risk score showed a Receiver Operating Characteristic Area Under Curve (AUC) of 0.837 for the prediction of admission for this large cohort of COVID-19 positive patients. Conclusion: The Mayo Clinic COVID-19 risk score is a simple score that is easily integrated into the EHR with excellent predictive performance for severe COVID-19. It can be leveraged to stratify risk for severe COVID-19 at initial contact, when considering therapeutics or in the allocation of vaccine supply.

Abstract Background The multiplex gastrointestinal pathogen panel (GIP) is a convenient and quick diagnostic test for determining the infectious etiology of diarrhea. It identifies several of the most common pathogens associated with gastroenteritis. However, it is expensive, and test results may not impact care, given that several of the pathogens in the panel are managed expectantly. We describe our experience with a diagnostic stewardship initiative to resolve the overuse of this testing method. Methods We performed a pre/post study of GIPs ordered for inpatients 18 years old and older from December 19, 2018, to December 18, 2020, at Mayo Clinic hospital in Rochester, Minnesota. GIP orders for inpatients were limited to the first 72 hours of hospitalization starting December 19, 2019. Orders after 72 hours were encouraged to be changed to Clostridioides difficile NAAT testing or sent to an infectious disease provider to override on a case-by-case basis. Our hospitals used BioFire® FilmArray® Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City, Utah). Results A total of 2,641 GIPs were performed during the study period. There were 1,568 GIPs (3.3/100 hospitalizations) in the pre-intervention period compared to 1,073 (2.6/100 hospitalizations) post-intervention, representing a drop of 21.2%. The most common pathogen detected was C. difficile (toxin A/B) (48.8%, n=402), followed by norovirus (17.5%, n=144). The overall test positivity rate was 27.9% (n=736). The test positivity rate decreased 1.8% from 28.6% (n=448) to 26.8% (n=288) after the restriction (p=0.33). The proportion of C. difficile among all pathogens detected increased from 48.5% to 49.7% (p=0.67). Table 1. Pre- and Post-Intervention Test Positivity Rate of Specific Pathogens in GIP Conclusion Our study showed that restricting the ordering of GIP to the first 72 hours of hospitalization and directing providers to standalone C. difficile NAAT testing resulted in a reduction of GIPs performed. There were marginal changes in the test positivity rate of GIP. A limitation of our study is that the timing of post-intervention coincided with the COVID-19 pandemic, which had unpredictable effects on hospital practice and patient admissions. Ideally, future quality improvement projects should increase the test positivity of pathogens other than C. difficile while lowering the GIP use in diagnosing C. difficile colitis. Disclosures John C. O'Horo, Sr., MD, MPH, Bates College and Elsevier Inc (Consultant)

Abstract Background We describe and compare the clinical, diagnostic evaluation and outcomes of patients who underwent therapeutic management for pyogenic brain abscess. Methods We retrospectively reviewed adults who presented with pyogenic brain abscess from January 1, 2009 through June 30, 2020. Results 231 patients were identified during the study period. Sixty-one (26.4%) patients received antibiotic therapy alone, and 170 (73.6%) had a combination of antibiotic therapy and surgical intervention. The median age for the medical and combined therapy group was 59 years and 58 years, respectively. Patients who received medical treatment had a higher prevalence of infective endocarditis than those who received combined therapy (6.6% vs. 0.6%; P=0.005). The medical therapy group was more likely to have brain MRI and cranial CT than the patients with combined therapy (75.4% vs. 63.5%; P=0.041). Midline shift (11.5% vs. 31.2%; P=0.002), a single (21% vs. 83%; P=0.001) and greater size (1.4 cm vs. 2.5 cm; P=0.007) brain abscess was significant when comparing medical vs. surgically managed abscess. Stereotactic surgical technique was the preferred diagnostic approach for the medical group (65.6% vs. 46.5%; P=0.010), and excision/craniotomy for the combined group (31.1% vs. 53.5%; P=0.002). Streptococcus viridans group was the predominant organism (32.8% and 25.9%; P=0.30). Compared to those who received combined therapy, patients with medical therapy alone were most likely to receive cephalosporin (72.1% vs. 41.2%; P=&lt; 0.0001), vancomycin (23% vs. 12.4%; P=0.047) and metronidazole (27.9% vs. 14.7%; P=0.022). In both groups, median duration of antimicrobial therapy was 42 days (P=0.12). Patients with medical therapy alone had a higher mortality rate (18% vs. 7.1%; p=0.014) but less neurologic sequelae (21.3% vs. 30.6%; P=0.16) compared with combined therapy. Medical Management. Organism isolated in the medical management group Combined Management. Organism isolated in the combined management group Demographic and Clinical Characteristics of Patients with Brain Abscess who Underwent Therapeutic Management Conclusion Most patients with pyogenic brain abscess had no identified risk factors, and brain MRI and cranial CT were the diagnostic imaging modalities of choice. Compared to those who received medical therapy alone, patients with combined treatment had a single and greater size fluid collection with the presence of midline shift. A prompt combined surgical and medical approach with prolonged antimicrobial therapy can cure the infection. Outcomes of Patients with Bacterial Brain Abscess Radiologic and Surgical Diagnosis of Patient with Brain Abscess who Underwent Therapeutic Management Disclosures John C. O’Horo, Sr., MD, MPH, Bates College and Elsevier Inc (Consultant) M. Rizwan Sohail, MD, Medtronic Inc., Philips, and Aziyo Biologics, Inc (Consultant) M. Rizwan Sohail, MD, Aziyo Biologics (Individual(s) Involved: Self): Consultant; Philips (Individual(s) Involved: Self): Consultant

Abstract Objectives Despite low rates of bacterial coinfection in patients admitted with COVID-19, antimicrobials are frequently prescribed. Our primary objective was to evaluate antimicrobial prescribing over time in patients admitted with COVID-19. The secondary objectives were to evaluate the role of ID providers in antimicrobial utilization, describe the rate of confirmed bacterial infection and determine factors associated with empirical antimicrobial prescribing in COVID-19. Materials and methods Retrospective review was performed for adult patients admitted to a tertiary care centre with COVID-19 between 1 March 2020 and 30 November 2020. Patient demographics, disease severity, risk factors for severe disease, clinical outcomes, antimicrobial prescribing and respiratory microbiological testing were collected and analysed. Prescribing trends were evaluated by month, and factors contributing to prescribing were established using univariate and multivariable analysis. Results Antibiotics were prescribed during admission in 37.9% of the study cohort, with 85.1% of patients who received antibiotics having therapy initiated within 48 h of admission. Antibiotic prescribing incidence increased with disease. Over the study period, antimicrobial prescribing rates decreased by 8.7% per month. Multivariable analysis found ICU admission, obtainment of procalcitonin values, intubation, heart failure, haemodialysis and nursing home residence were associated with empirical antimicrobial prescribing. Conclusions Unnecessary antimicrobial prescribing in patients with viral syndromes like COVID-19 continues to represent an area of concern. Antimicrobial stewardship efforts during COVID-19 should consider patient-specific factors associated with antibiotic prescribing. Recognition of such factors, in combination with application of well-established antimicrobial stewardship tactics, may serve to impact antimicrobial prescribing trends, even as patient volumes rise.