Chesdachai, Supavit

AbstractIn this clinicopathological conference, invited experts discussed a previously published case of a patient with nonischemic cardiomyopathy who underwent heart transplantation from a genetically modified pig source animal. His complex course included detection of porcine cytomegalovirus by plasma microbial cell‐free DNA and eventual xenograft failure. The objectives of the session included discussion of selection of immunosuppressive regimens and prophylactic antimicrobials for human xenograft recipients, description of infectious disease risk assessment and mitigation in potential xenograft donors and understanding of screening and therapeutic strategies for potential xenograft‐related infections. image

Abstract Background The treatment of invasive fungal infections (IFI) is often complicated by drug-drug interactions, toxicities, and host comorbidities. Isavuconazole (ISA) has a favorable side effect profile and has FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data on its efficacy for other microbes and non-pulmonary infections. We report our experience of ISA in IFI treatment, with a particular focus on non-pulmonary sites and other microbial etiologies. Methods We identified patients who received ISA as part of IFI treatment from 1/1/2015–4/1/2020 at Mayo Clinic. We categorized them by organ involvement and by pathogens, and identified patterns of ISA use and clinical outcomes. Results A total of 131 patients were identified. Similar to the existing literature, the majority were pulmonary infections (60%), with 12% invasive sinus infection, 12% central nervous system (CNS) infection, and 7% fungemia. Aspergillus was the most common pathogen (39%), yeast comprised 19%, dimorphic fungi 15%, Mucormycosis 12%, phaeohyphomycosis 5%, and other molds 3%. ISA was used as secondary/salvage therapy in 89% of cases. The response rate varied by organ involvement and pathogen. ISA had complete/partial resolution or achieved stability in 57% of fungemia cases, 63% of invasive sinus infections, 64% of pulmonary infections, and 73% of CNS infections. Aspergillus species had a 67% response rate, with 72% response in yeast infections, 65% rate in dimorphic fungi, 53% for mucormycosis, and 86% in dematiaceous molds. Conclusion Although limited by a small sample size, the subgroup review based on organ site and microbial etiology did seem to show roughly similar results to approved uses. The CNS infections treated with ISA were particularly of interest, given the limited options available with reliable CNS penetration. The current available literature has little to say on the efficacy of ISA in these off-label uses, with the majority being similar case series. This report highlights the importance of prospective trials comparing ISA to other antifungals in a greater variety of indications to better identify when this better-tolerated agent can be safely used. Disclosures Courtney E. Harris, MD, Dynamed: Advisor/Consultant

Abstract Background Two independent placebo-controlled clinical trials conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness have not been directly compared. Methods This retrospective study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Results Among 3,257 patients, 2,158 received sotrovimab and 1,099 received remdesivir. Patients treated with sotrovimab were younger (median age, 60 vs. 69 years) and had lower comorbidity (Monoclonal Antibody Screening Score, 5 vs. 6; Charlson Comorbidity Index, 3 vs. 4), but were more likely to be immunocompromised (47.3% vs. 30.2%) than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine (median, 3 doses [IQR 2-3] for both groups). COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab groups, respectively, p=.15) and mortality within 28 days (0.4% in both groups, p=.82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the rates of COVID-related hospitalization and death within 28 days between the two groups. Conclusion This study demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab. As sotrovimab is no longer authorized, these results support the continued use of remdesivir for treating high-risk patients with COVID-19 during the current Omicron-predominant epoch. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Maria Gonzalez Suarez, M.D., Ph.D., Gilead: Grant/Research Support Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Background Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In prior work, those who continued remdesivir in an outpatient setting had better outcomes. Here, we assessed patients’ perspectives and the economic impact of this outpatient practice. Methods During a one-year period, 3,029 patients received remdesivir for COVID-19 in the hospital; of them, 542 were dismissed to continue remdesivir in the outpatient setting and were surveyed. The cost of care was compared between those who remained in the hospital vs. those who were dismissed. Results 470 of 542 patients were surveyed, and 93 (19.8%) responded. Responders were older than non-responders (median, 63 vs. 58 years). The majority (70.5%) had symptoms resolved by the time of the survey. Ten patients (11.4%) had persistent symptoms attributed to long COVID-19, including fatigue (30.1%), brain fog (23.7%), and insomnia (18.3%). 73.8% were excited to learn about the outpatient remdesivir program. The majority (81.0%) felt that receiving therapy at home was the right decision; 79.5% had support and felt the benefits of completing treatment at home. The majority were satisfied with communication before (75.6%) and during (80.5%) the outpatient appointment, information on benefits (80.3%) and risks (58.5%), time spent at the infusion center (88.6%), quality of care (82.3%) and overall experience (76.0%). The benefits of treatment were high-value (82.6%), while the infusions' cost, inconvenience, and discomfort were unimportant for most responders. After adjusting for gender, comorbidity score, and WHO scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p< .01). During this study, we estimated a total of 1,077 hospital room-days were made available to other patients. Conclusion An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients hospitalized for COVID-19. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital rooms for other patients needing critical services. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Bijan J. Borah, Ph.D., Boehringer Ingelheim: Advisor/Consultant|Exact Sciences: Advisor/Consultant Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support

Abstract Background Staphylococcus aureus bacteriuria (SABU) represents 0.2–4% of all positive urine cultures. While asymptomatic colonization or infection of the urinary tract is possible, hematogenous seeding from S. aureus bacteremia (SAB) represents a potentially life-threatening condition. The rate of concomitant SAB is estimated to be 6.9–17.2% among those with SABU, and these patients are at higher risk of in-hospital mortality, infective endocarditis, embolic events, and vertebral osteomyelitis. Detection of SABU represents an opportunity for early detection and intervention in SAB. Methods We conducted a retrospective analysis of clinical and microbiological characteristics of adult patients with SABU as our pre-intervention baseline. We then implemented a comment with the urine culture result in the electronic medical record (EMR) advising providers about the possibility of concomitant bacteremia. We conducted an interim analysis of early post-intervention data. Figure 1: Study Workflow Figure 1: Study workflow depicting case recruitment and blood culture results. Figure 2: Intervention Flag Figure 2: Example of intervention comment displayed with the urine culture result in the EMR. Results 250 adult patients developed SABU from January 1, 2021, to January 31, 2023. Of these, 87 (34.8%) had urinary tract symptoms, and 91 (36.4%) had a chronic indwelling urinary catheter. 74 (29.6%) patients had blood cultures collected within 7 days of positive urine culture. The presence of urinary symptoms or indwelling catheter was not associated with blood culture collection. Only 22 patients (8.8%) had SAB with SABU. One patient was diagnosed with SAB 20 days after detection of SABU with infective endocarditis and disseminated infection, representing a delay in diagnosis. Following implementation of the intervention, an additional 86 patients with SABU had the result comment displayed in the EMR. Blood cultures were collected in 19 (22.1%) patients, and 2 (2.3%) were positive for S. aureus. There were no significant differences in rates of blood culture collection or SAB after implementation of the EMR result comment. Conclusion Our results show a similar rate of SABU associated SAB to that previously reported in the literature. Delayed diagnosis of SAB in SABU is uncommon but does occur rarely with significant morbidity. The addition of a result comment is a simple and cost-effective intervention; however, evaluation of its efficacy is presently limited by a short follow-up duration. Disclosures All Authors: No reported disclosures

Abstract Background Human granulocytic anaplasmosis (HGA) is an emerging tick-borne illness endemic to the northeastern and midwestern United States. Risk factors for the severity of infection, predictors for hospitalization, temporal trends, co-infections, and outcomes are poorly studied. Methods We conducted a retrospective review of HGA at Mayo Clinic, Rochester, between 2011-2021. Cases were identified by positive Anaplasma PCR at our reference laboratory. Variables included patients’ characteristics, symptoms, risk factors for tick-borne illness, laboratory parameters, co-infections, treatment, and clinical outcomes. Results We identified 471 cases with a positive Anaplasma PCR, and 146 cases were included in this interim analysis. Table 1 shows a summary of the baseline characteristics. An increasing annual trend in diagnosis of HGA was noted from 2014 to 2016 with lower rates observed during COVID-19 pandemic (2020 to 2022) (Figure 1). Of the 146 patients, 19 (13%) were immunocompromised secondary to hematologic malignancies, solid organ malignancies, and pharmacological immunosuppression. Frequently reported symptoms included fever (79.5%), malaise (68.5%), chills (51.4%), and myalgia (50%). Tick exposure was documented in 79.2 % of cases. Forty-seven (33%) patients were hospitalized; older patients were more likely to be hospitalized (Table 2). The most common complications among the hospitalized patients included respiratory failure (50%), encephalopathy (44.4%) and renal failure (37.5%). One patient required ICU admission. Twenty-five patients (17.5%) and one patient (0.7%) were co-infected with Lyme and Ehrlichiosis, respectively. Higher rates of leukopenia and thrombocytopenia were associated with mono-infection with Anaplasma (p < 0.001). Follow up data was available for 136 patients; all of them had favorable response to doxycycline.Table 1:Summary of baseline characteristics, labs and treatment.Table 2:Predictors of HospitalizationFigure 1:Annual Trends in Anaplasmosis from 2011-2021. Conclusion Our study demonstrated comprehensive clinical characteristics of patients with HGA. Interestingly, tick exposure history was common, yet most patients did not have other tick-borne co-infections. Furthermore, only a minority of patients developed severe diseases and required hospitalization. The recent decline in cases during the early part of the COVID-19 pandemic is worth further investigation. Disclosures All Authors: No reported disclosures

Abstract Background Patent foramen ovale (PFO) can be identified in about 20-25% of the adult population and may result in variable degrees of left-to-right and right-to-left intracardiac shunting. The association between PFO and pyogenic brain abscess remains poorly understood. The current study aimed to compare the clinical characteristics and outcomes of pyogenic brain abscess in patients with and without PFO. Methods All adults with pyogenic brain abscess seen at Mayo Clinic from 1/1/2009-12/31/2021 who underwent either transesophageal echocardiography (TEE) or transthoracic echocardiography (TTE) with agitated saline shunt (bubble) study were included. Results A total of 222 patients developed pyogenic brain abscess during the study period; 148 (66.7%) patients were excluded due to unknown PFO status. Among 74 remaining patients, PFO was detected in 30 (40.5%) patients; 25 by TEE and 5 by TTE with bubble study (Figure 1). The prevalence of cryptogenic brain abscess (unable to identify the source of abscess) was significantly higher in patients with PFO as compared to those without PFO (53.3% versus 18.2%, p=0.002). Patients with PFO had a larger abscess size (25 mm [IQR 15.8-37.5] versus 15.5 mm [IQR 10.0-28.0], p=0.038). However, multiple abscesses were more common in the group without PFO (43.2% versus 20.0%, p=0.038). Additionally, patients with PFO had less documented bloodstream infection. There were no differences between other clinical characteristics and one-year, all-cause mortality between two groups. Conclusion These findings provide critical insights into the likely association between PFO and cryptogenic brain abscess; additional investigation is warranted. Disclosures Larry M. Baddour, MD, Boston Scientific: Advisor/Consultant|Roivant Sciences: Advisor/Consultant

Abstract Background Achromobacter spp. are important pathogens that are most frequently implicated in opportunistic infections, especially in patients with chronic lung disease, malignancy, and solid organ or hematopoietic stem cell transplantations. They commonly cause pneumonia, bacteremia, and device-associated infections. Intrinsic and acquired resistance mechanisms usually complicate treatment. Further characterization of the changing antibiotic susceptibilities and clinical manifestations of Achromobacter spp. are needed to improve clinical practice. Methods We performed a retrospective review of Achromobacter isolates from 2013 to 2023 in the Mayo Clinic Enterprise with available antimicrobial susceptibility testing (AST) data. Variables included sample source, collection date, and AST by agar dilution with susceptibility defined according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. Samples were categorized into quartiles based on collection date and grouped into source types (respiratory, genitourinary, etc.) and AST. Results A total of 1,506 patients were identified with a total of 1,546 unique Achromobacter spp. isolates from 2013 - 2023. The most common species was A. xylosoxidans, encompassing 40.1% of all isolates (Table 1). Respiratory samples (sputum, bronchoalveolar lavage) were the most common source (57.5%), followed by musculoskeletal and soft tissue (16.4%), genitourinary (12.2%), and oropharyngeal sources (10.3%). AST from 2013 to 2023 showed persistent high levels of resistance to aztreonam and tetracycline, with stable susceptibility to piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and carbapenems (Table 2). Over our 10-year analysis, there was increased resistance to aminoglycosides, fluoroquinolones, ceftazidime, and cefepime.Table 1.Achromobacter Species Identification and Isolate Percentage (%) Stratified by Year Table 1 lists the Achromobacter species identified stratified by the year each sample was collected. Each value represents the number of isolates that were identified as the listed Achromobacter species, with "Achromobacter sp." indicating an isolate without species identification. Percentages of species are listed in parentheses (%). Sample totals are listed in the right column.Table 2.Antibiotic Susceptibility of All Tested Achromobacter Isolates (Percentage of Susceptible Isolates) Table 2 lists antibiotics by class, stratified by year that Achromobacter isolates were tested. Each value is the total number of isolates tested for antimicrobial susceptibility, followed by the percentage of susceptible isolates in parentheses (%). Total isolates tested and overall susceptibility percentage is also listed over the 10-year period. Conclusion Achomobacter continues to be a clinically significant organism with a complex resistance profile. Our dataset shows a significant prevalence of non-respiratory and non-genitourinary samples, in addition to increasing resistance over many antibiotic classes. Our data suggests that piperacillin-tazobactam, imipenem, and minocycline are appropriate empiric regiments for Achromobacter. Disclosures All Authors: No reported disclosures

Abstract Background Limited research has focused on bloodstream infection (BSI) in patients with arterial grafts. This study aims to describe the incidence and outcomes of BSI after arterial aneurysm repair in a population-based cohort. Methods The expanded Rochester Epidemiology Project (e-REP) was used to analyze aneurysm repairs in adults (aged ≥18 years) residing in 8 counties in southern Minnesota from January 2010 to December 2020. Electronic records were reviewed for the first episode of BSI following aneurysm repair. BSI patients were assessed for vascular graft infection (VGI) and followed for all-cause mortality. Results During the study, 643 patients had 706 aneurysm repairs: 416 endovascular repairs (EVARs) and 290 open surgical repairs (OSRs). Forty-two patients developed BSI during follow-up. The 5-year cumulative incidence of BSI was 4.7% (95% confidence interval [CI], 3.0%–6.4%), with rates of 4.0% (95% CI, 1.8%–6.2%) in the EVAR group and 5.8% (95% CI, 2.9%–8.6%) in the OSR group (P = .052). Thirty-nine (92.9%) BSI cases were monomicrobial, 33 of which were evaluated for VGI. VGI was diagnosed in 30.3% (10/33), accounting for 50.0% (8/16) of gram-positive BSI cases compared to 11.8% (2/17) of gram-negative BSI cases (P = .017). The 1-, 3-, and 5-year cumulative post-BSI all-cause mortality rates were 22.2% (95% CI, 8.3%–34.0%), 55.8% (95% CI, 32.1%–71.2%), and 76.8% (95% CI, 44.3%–90.3%), respectively. Conclusions The incidence of BSI following aneurysm repair was overall low. VGI was more common with gram-positive compared to gram-negative BSI. All-cause mortality following BSI was high, which may be attributed to advanced age and significant comorbidities in our cohort.

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.