Ilges, Dan

AbstractTixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre‐exposure prophylaxis against COVID‐19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID‐19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID‐19 infection, severity of COVID‐19 infection, graft function, and rejection. Safety outcomes included cardiovascular (CV) and hypersensitivity events post tix/cil administration. A total of 410 transplant patients were included in the analysis: 20 heart, 92 liver, 243 kidney, 25 simultaneous pancreas/kidney, 23 simultaneous liver/kidney, and seven simultaneous heart/kidney. Twenty‐seven (6.5%) patients tested positive for COVID‐19 via PCR or antigen test post tix/cil. No apparent difference was observed in patients testing positive for COVID‐19 by type of organ transplant (p = .122). Twenty‐five of the 27 patients testing positive for COVID‐19 reported symptomatic infection, only nine of whom were hospitalized. No patients were mechanically ventilated and no deaths due to COVID‐19 occurred. No significant changes in graft function were observed. Clinically significant rejection was diagnosed and treated in four patients. COVID‐19 breakthrough infection rates remained low in immunocompromised solid organ transplant recipients who received tix/cil. No significant immunologic risks were observed.

Abstract Background The BioFire® FilmArray® Gastrointestinal Pathogen Panel (GIPP) tests for 22 potential pathogens in stool, including Clostridioides difficile. C. difficile nucleic acid is detected via nested polymerase chain reaction (PCR) targeting toxin A (TcdA) and/or toxin B (TcdB) genes. While PCR-based diagnostic methods are highly sensitive, they lack specificity to differentiate colonization from C. difficile infection (CDI). Mayo Clinic Arizona (MCA) uses enzyme immunoassay (EIA) testing for toxin A/B and glutamate dehydrogenase antigens with reflex to PCR for discordance as the primary algorithm for diagnosing CDI; however, GIPP PCR testing circumvents this algorithm. When used in patients with low pretest probability for CDI, clinical false positives can lead to inappropriate diagnosis and treatment of colonization. GIPA Results in the Electronic Medical Record Pre-Intervention MCA Standalone C. difficile Testing Algorithm Abbreviations – EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test Methods We convened a multidisciplinary quality improvement team to reduce the detection and treatment of C. difficile colonization secondary to GIPP test results. Surveys were sent to providers and nurses as part of a formal gap analysis and included questions around ordering patterns, knowledge of appropriate tests, and associated costs. Baseline data was compiled from GIPP orders in MCA from 1/1/2022-9/30/2022. Results There were 1978 GIPP orders for 1694 patients during the study period (∼7 GIPPs/day). Most orders (65%) originated from ambulatory settings. The most common positive target was C. difficile (355/723, 49%), which resulted in treatment for suspected CDI in 94.9% (337/355) of cases. Of the 49 providers who responded to the survey, 86% ordered the GIPP at least monthly. Testing for C. difficile was the 2nd most common reason for ordering the GIPP. Most providers underestimated the cost of the panel and were unfamiliar with the differences between the GIPP and EIA testing algorithm. Nurses sought clarification on stool samples suitable for GIPP testing. Following education and modifications to ordering in the electronic health record, the decision was made to remove the C. difficile target from the GIPP. Provider Understanding of C. difficile Testing Methods GIPA Results in the Electronic Medical Record Post-Intervention Conclusion Multiplex PCR panels are comprehensive but require careful implementation to facilitate diagnostic stewardship. Facilities with robust standalone C. difficile testing algorithms may consider removing the C. difficile target from the GIPP. Disclosures All Authors: No reported disclosures

Abstract Background Inappropriate use of carbapenems is a major driver of antimicrobial resistance. The intensive care unit (ICU) at Mayo Clinic Arizona had a higher meropenem (MER) days of therapy (DOT) per 1000 patient days (PD) compared to other Mayo Clinic Enterprise sites, despite low rates of Pseudomonal resistance to narrower spectrum anti-pseudomonal beta-lactams. Methods A multidisciplinary team of infectious diseases (ID) and critical care medicine (CCM) physicians and pharmacists was created to reduce inappropriate use of MER in the ICU. The baseline rate of appropriateness was determined by evaluating all MER days in the ICU during Q4 2019 and Q4 2020. Each MER day was designated as appropriate or inappropriate based on pre-determined criteria after review by at least one ID and one CCM member. Discordant days were evaluated by the whole team to achieve consensus. The team provided education to the CCM department on the initiative, baseline data, and strategies to reduce inappropriate MER use. The active intervention included prospective audit and feedback of all patients on MER performed by the ID clinical pharmacists Mon-Fri 0700-1530 in Q4 2022. DOT/1000 PD was assessed for the pre-intervention and intervention periods. Results The baseline rate of inappropriate MER use in the ICU was 52% (442/846 days). The two most common reasons for inappropriate MER use in the baseline period were: susceptible organism for which a narrower agent could have been used (93/442, 21%), and infectious workup/cultures negative (89/442, 20%). During the intervention period, the inappropriate rate of MER use was reduced to 23%, below the pre-determined goal of 30%. The MER DOT/1000 PD in the baseline period were 103.9 (Q4 2019) and 151.5 (Q4 2020) versus 66.1 (Q4 2022) in the intervention period. There was no difference in ICU sepsis-related mortality in the pre-intervention vs intervention period (13.4 vs 0%, p=0.04). Conclusion A multidisciplinary team approach, including education and prospective audit and feedback, reduced inappropriate MER use in the ICU of an academic medical center from 52 to 23%. An associated decrease in MER DOT/1000 patient days was also observed. Disclosures All Authors: No reported disclosures

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 Days of therapy (DOT) currently serve as the standard antimicrobial utilization metric. However, by assigning the same weight to each agent rather than accounting for differences in spectrum of activity, DOT ignore key differences between agents that are fundamental to infectious diseases and critical to antimicrobial stewardship. Spectrum scoring assigns numeric values to individual antibiotic agents to quantify their spectrum of activity, allowing for the normalization of antibiotic utilization data. When used in conjunction with traditional metrics, spectrum scores may offer further clarity to antibiotic utilization; however, issues related to development, application, and standardization of spectrum scores remain. Despite these challenges, the potential applications of spectrum scores are vast. Here, we summarize existing data and explore the future of spectrum scoring, including application to both data analysis and routine patient care, use in inpatient and outpatient settings, integration within the electronic medical record, and opportunities for future research.

IMPORTANCE: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection, accounting for 22% of all nosocomial infections. The available studies to date have not attempted to assess whether confounding factors may account for the observed difference in mortality for the two forms of nosocomial pneumonia associated with mechanical ventilation, namely ventilated HAP (vHAP) and ventilator-associated pneumonia (VAP). OBJECTIVES: To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Single-center retrospective cohort study conducted at Barnes-Jewish Hospital, St. Louis, MO, between 2016 and 2019. Adult patients with a pneumonia discharge diagnosis were screened and patients diagnosed with vHAP and VAP were included. All patient data was extracted from the electronic health record. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause mortality (ACM). RESULTS: One thousand one-hundred twenty unique patient admissions were included (410 vHAP, 710 VAP). Thirty-day ACM was greater for patients with vHAP compared with VAP (37.1% vs 28.5%; p = 0.003). Logistic regression analysis identified vHAP (adjusted odds ratio [AOR], 1.77; 95% CI, 1.51–2.07), vasopressor use (AOR, 2.34; 95% CI, 1.94–2.82), Charlson Comorbidity Index (1-point increments) (AOR, 1.21; 95% CI, 1.18–1.24), total antibiotic treatment days (1-d increments) (AOR, 1.13; 95% CI, 1.11–1.14), and Acute Physiology and Chronic Health Evaluation II score (1-point increments) (AOR, 1.04; 95% CI, 1.03–1.06) as independent predictors of 30-day ACM. The most common bacterial pathogens identified as causes of vHAP and VAP were Staphylococcus aureus, Enterobacterales species, and Pseudomonas aeruginosa. CONCLUSIONS AND RELEVANCE: In this single-center cohort study with low rates of initial inappropriate antibiotic therapy, vHAP had greater 30-day ACM compared with VAP after adjusting for potential confounding variables including disease severity and comorbidities. This finding suggests that clinical trials enrolling patients with vHAP need to account for this outcome difference in their trial design and data interpretation.

Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) are associated with significant morbidity and mortality. MSSA BSIs can rapidly disseminate, resulting in deep-seated infections, prolonged durations of bacteremia, and further metastases. Recently, cefazolin and ertapenem combination therapy has emerged as a potential therapeutic strategy to sterilize the blood in patients with persistent MSSA bacteremia. Here, we present a patient with COVID-19 pneumonia and concomitant MSSA BSI achieving blood culture sterilization within 24 hours of cefazolin and ertapenem combination therapy initiation following 11 days of positive blood cultures.