Citations

Abstract Telomeres are regions of repetitive DNA at the ends of linear chromosomes which protect chromosome ends from degradation. Telomere lengths have been extensively studied in the context of aging and disease, though most studies use average telomere lengths which are of limited utility. We present a method for identifying all 92 telomere alleles from long read sequencing data. Individual telomeres are identified using variant repeats proximal to telomere regions, which are unique across alleles. This high-throughput and high-resolution characterization of telomeres could be foundational to future studies investigating the roles of specific telomeres in aging and disease.

AbstractIntroductionGram‐negative bacillary bloodstream infection (GN‐BSI) is a frequent clinical challenge among immunocompromised hosts and is associated with a high mortality. The utility of follow‐up blood cultures (FUBCs) for GN‐BSI in this population, particularly in the setting of neutropenia, is poorly defined.MethodsWe conducted a single‐center, retrospective cohort study between the period of July 2018 and April 2022 to investigate the utility of FUBCs and delineate risk factors for positive cultures among neutropenic patients with monomicrobial GN‐BSI. Univariate logistic regression was performed to assess risk factors associated with positive FUBCs.ResultsOf 206 patients, 98% had FUBCs performed, and 9% were positive. Risk factors for positive FUBCs included multidrug‐resistant GN infection (OR 3.26; 95% confidence interval [CI] 1.22–8.72) and vascular catheter source (OR 4.82; CI 1.76–13.17). Among patients lacking these risk factors, the prevalence of positive FUBCs was low (2.8%) and the negative predictive value was 92%. Those with positive and negative FUBCs had similar rates of all‐cause mortality (16.7% vs. 16.6%; p = .942) and microbiologic relapse (11.1% vs. 6.0%; p = .401) within 90‐days of treatment completion. However, positive FUBCs were associated with prolonged hospitalization and longer duration of antimicrobial therapy.ConclusionPositive FUBCs were infrequent in neutropenic patients with GN‐BSI, and their occurrence did not significantly impact mortality or microbiologic relapse. Risk factors for positive FUBCs included multidrug resistant Gram‐negative infection and vascular catheter source. Prospective studies will be necessary to elucidate the benefits and risks of FUBCs when managing GN‐BSI in patients with underlying immune compromise. image

Abstract Background There is scarce data surrounding the epidemiology of invasive fungal infections (IFI) after pancreas transplantation (PT). Our centers’ PT protocols recommend universal fluconazole prophylaxis for at least 1 month, which is extended to 1 year for recipients who live in Coccidioides endemic areas. The purpose of our study was to evaluate the epidemiology of IFIs after PT while on our antifungal prophylaxis protocol. Methods A retrospective cohort study was performed among adult patients who underwent PT at Mayo Clinic sites in Arizona, Florida, or Minnesota between January 1, 2010 and December 31, 2020. IFI was defined based on EORTC/MSGERC criteria. The primary aim was to describe epidemiology and timing of IFI after PT, particularly in the context of the universal antifungal prophylaxis protocol. Results Among 482 pancreas transplant recipients, 35 developed IFIs (7.3%). All patients received antifungal prophylaxis per protocol for a median duration of 33 days (Figure 1). Median duration from time of transplant to IFI was 16 (IQR 10.5-28.2) days for Candida IFIs versus 529 (IQR 192.5-1195.0) days for non-Candida IFI. 20 IFIs (57.1%) were secondary to Candida species with 45% of these cases caused by either C. glabrata or C. krusei (Figure 2). 90% were on antifungal prophylaxis (85% fluconazole) at time of diagnosis of invasive candidiasis. All the Candida IFIs were intra-abdominal infections. Amongst the 15 non-Candida IFIs (42.9%), 9 were secondary to endemic mycoses and 4 were secondary to invasive molds. Conclusion Our study shows a high incidence of IFIs secondary to Candida, with few patients diagnosed with non-Candida IFIs (Figure 3). Non-Candida IFIs, mostly secondary to endemic mycoses, occurred more than a year after transplant. Patients are at highest risk for Candida IFIs within the first 30 days after PT, likely secondary to organ space surgical site infections, despite receipt of antifungal prophylaxis. Breakthrough invasive candidiasis occurred in 90% of cases. Though our study lacked a comparator group without prophylaxis, these data question the effectiveness of fluconazole prophylaxis after PT. Disclosures All Authors: No reported disclosures

Abstract Background Majocchi’s granuloma (MG) is an uncommon deep fungal folliculitis predominantly caused by dermatophytes. Available data regarding predisposing comorbidities/risk factors, clinical characteristics, offending microbiologic pathogens, diagnostics, pathologic findings, and treatment approaches has been inferred from historical cases. Given these limitations in the existing literature of MG, we sought to conduct a detailed review of our institutional experience with biopsy-confirmed cases of MG. Methods Following IRB approval, we retrospectively identified and analyzed a multicenter cohort of adult patients diagnosed with MG between September 1992 and September 2022 at Mayo Clinic campuses (Figure 1). Data extracted included demographics, comorbid conditions, presenting clinical characteristics, diagnostic, microbiologic, and biopsy characteristics, treatment details, and outcomes. Figure 1 Flow Diagram show exclusion of patients from the final cohort. Results A total of 147 patients with MG with the accompanying baseline characteristics met study criteria (Table 1). One-hundred and five patients were male with a median age of 55.6 years. Immunosuppressant and topical corticosteroid use were common prior to development of MG (Table 1). Dermatologic lesions and their sites of involvement did not differ based on the immune status of patients (Table 2). Trichophyton rubrum was the most common causative pathogen of MG, in addition to other dermatophytes and fungal organisms (Table 3a). Treatment duration for all prescribed agents was median 31.5 days. Oral terbinafine was the most frequently utilized agent and clinical resolution was achieved in 96.6% of cases (Table 3b). Baseline Characteristics of 147 Patients with Majocchi’s Granuloma Diagnostic, Microbiologic, and Biopsy Characteristics, Treatment Characteristics and Outcomes Conclusion While rare and clinically variable in presentation, the diagnosis of MG requires careful clinical examination and history-taking, histopathologic confirmation, and frequently fungal culture. Most cases of MG in our study responded well to a course of oral terbinafine at a median of 31.5 days of treatment. Disclosures All Authors: No reported disclosures

Abstract Background Vancomycin resistant enterococcus (VRE) infective endocarditis (IE) is associated with poor outcomes. There are limited data to guide the antimicrobial choice and duration of therapy. Several in vitro and limited clinical studies demonstrate the synergistic effect of β-lactams with other agents, particularly daptomycin, in this setting. We sought to compare clinical outcomes in patients with VRE IE treated with adjunctive β-lactam therapy. Methods This was an IRB-approved, retrospective, single-center cohort study. The study included patients ≥18 years of age diagnosed with VRE IE via modified Duke criteria from 2011-2021. Data were collected by electronic medical record review. Descriptive statistics were obtained. The primary outcome was 90-day treatment failure compared between those receiving and not receiving adjunctive β-lactams. Treatment failure was defined as recurrence of bloodstream infection (BSI) or death within 90 days of diagnosis. Failure-free survival was analyzed by Kaplan-Meier curve with log-rank test. Results A total of 32 cases were identified. 12 received adjunctive β-lactams. Mean age was 67 years, and 71% were male. 13 (41%) had a prosthetic valve and 6 (19%) had a CIED (Table 1). A majority (78%) had E. faecium IE. Mean duration of bacteremia was 9 days (Table 2). About one-third had treatment failure with 7 deaths and 4 BSI recurrences. Adjunctive β-lactams included ampicillin (3), cefepime (1), ceftaroline (6) and ceftriaxone (2). There was no statistical difference in failure-free survival in patients treated with adjunctive β-lactam therapy (Figure 1). The results were similar when restricted only to those who received daptomycin with or without adjunctive β-lactam therapy.Table 1.Patient CharacteristicsTable 2.Disease characteristics Figure 1. Kaplan-Meier curve comparing failure-free survival between patients who were primary treated with adjunctive β-lactams versus non-adjunctive therapy. The p-value is calculated via the log-rank test. Conclusion VRE IE is associated with poor prognosis, including high rates of mortality and relapses. In our experience, adjunctive B-lactam use did not result in improved outcome. Limitations include small sample size, and heterogenous antibiotic use. More prospective randomized data are needed. Disclosures All Authors: No reported disclosures

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 Clostridioides difficile infection (CDI) is a common and potentially life-threatening infection. Transplant recipients are vulnerable to CDI due to immune suppression and frequent antibiotic exposure. CDI can lead to serious complications in these patients, including allograft failure. In a population of pancreas transplant recipients, we aimed to identify epidemiologic characteristics and risk factors associated with CDI within 90 days of transplant. Methods We performed a retrospective cohort study of adults who underwent pancreas transplantation between January 1, 2010, and December 31, 2020, at three centers in Arizona, Florida, and Minnesota. Patients were excluded if they developed pancreas allograft failure within 48 hours of transplantation. The primary outcome was diagnosis of CDI within 90 days of transplantation and the secondary outcome was pancreas allograft failure. The main analyses were performed by Cox regression. Results A total of 482 patients were included, of which 35 (7.3%) developed CDI within 90 days (Table 1). Within the subset of 35 CDI patients, the median time to CDI was 17.0 (IQR 13.0–28.5) days (Figure 1) with most (83%) diagnosed with non-severe CDI. Most patients with CDI were on current systemic antibiotics (94%), primarily for prophylaxis (73%). CDI treatment was vancomycin for the majority of patients (71%) and metronidazole for the rest (29%). One patient had a fecal transplant for recurrence, and none required surgery. In multivariable cox regression of associations with 90-day CDI, significant associations were anastomotic leak (HR 3.04, 95% CI 1.2-7.4; p=0.015) and simultaneous pancreas-kidney transplantation (HR 8.70, 95% CI 1.15-66.7; p=0.036); age (HR 0.97, 95% CI 0.94-1.01; p=0.110) was not significant. In a secondary analysis, CDI was not associated with pancreas allograft failure (p=0.719).Table 1.Characteristics of 482 patients who underwent pancreas transplantation. Conclusion This study identified preceding anastomotic leak as a risk factor for 90-day CDI after pancreas transplantation, likely due to subsequent intra-abdominal infection and antibiotic use. simultaneous pancreas-kidney transplantation is another risk factor due to additional comorbidity. Transplant providers should be cognizant of the risks of CDI and mitigate these risks as possible. Disclosures All Authors: No reported disclosures

Abstract Background Eosinopenia has previously been studied as a predictor of bacteremia and sepsis, and has been identified as a marker of increased mortality in critically ill patients. To date, one study has examined changes in eosinophil count during bacterial infection, noting quicker normalization of eosinophil count versus traditional markers of inflammation, whereas no studies have examined eosinophil count recovery as a predictor of blood stream clearance. Methods We conducted a multicenter, retrospective cohort study of adult patients diagnosed with Staphylococcus aureus bacteremia (SAB) between January 2018 and December 2019 at Mayo Clinic campuses. Patients with eosinopenia on the date of the first positive blood culture were selected for further analysis. Eosinopenia was defined as an eosinophil count < 0.03 x10(9)/L. Eosinophil count recovery was defined as the first subsequent date where an eosinophil count ≥0.03 x10(9)/L was recorded. Clearance of SAB was defined as negative blood cultures at 48 hours on two consecutive days, and the date of clearance was defined as the date of first negative blood culture. Results A total of 213 cases of SAB were identified where an eosinophil count was obtained on date of first positive blood culture. Of these cases, 132 (62.0%) had eosinopenia at time of diagnosis. Data related to count recovery was available for 90 patients, with associated characteristics for this cohort detailed in Table 1. S. aureus isolates were oxacillin susceptible in 91.1% (82/90) of cases. The median time to clearance of bacteremia was 2.7 days (IQR 1.8-4.7 days), and the median time to eosinophil count recovery was 2.0 days (IQR 2.0-3.0 days). Data related to timing of eosinophil count recovery are presented in Table 2. Resolution of eosinopenia occurred within 48 hours of bloodstream clearance in 79/90 (87.8%) of cases and preceded or occurred within 48 hours of blood culture clearance in 88/90 (97.8%) of cases. Conclusion Eosinopenia is a common finding at time of diagnosis of SAB, and recovery of eosinophil count is suggestive of imminent clearance of blood cultures. Disclosures All Authors: No reported disclosures