McHugh, Jack

Abstract Background The aim of this study was to determine the incidence, epidemiology, and associated risk factors of bloodstream infection (BSI) in patients who had previously undergone cardiac valve repair. Methods A population-based study that included 7 counties in southeastern Minnesota using the expanded Rochester Epidemiology Project (e-REP) for adults (≥18 years) who underwent valve repair between 1 January 2010 and 31 December 2018 was conducted. Electronic health records were screened for development of BSI and infective endocarditis (IE) from the date of valve repair through 30 July 2020. A 1:4 nested case-control analysis was performed to determine an association, if any, of male sex, Charlson comorbidity index (CCI), and county of residence with BSI. Results A total of 335 patients underwent valve repair, of whom 28 (8.3%) developed an index case of BSI, with 14 episodes occurring within 1 year of surgery. The median age of patients with BSI was 70 years, and 79% were male. The crude incidence of BSI was 1671 cases per 100000 person-years and Escherichia coli was the most common pathogen. Case-control analysis demonstrated a significant correlation between CCI and incidence of BSI (P < .001). Only 4 (14.3%) patients developed IE concurrent with the onset of BSI, and no patients developed IE subsequent to BSI. Conclusions The crude incidence of BSI following valve repair was higher in our e-REP cohort than previous population-based studies, and half of the BSI cases occurred within 1 year of surgery. Patients with a higher CCI at baseline were at increased risk of subsequent BSI.

Background: Blastomycosis can cause severe disease with progressive respiratory failure and dissemination even in immunocompetent individuals. We sought to evaluate risk factors for severe disease and mortality using clinical and laboratory data within a large health system in an endemic area. Methods: We performed a retrospective cohort study of patients diagnosed with blastomycosis at all Mayo Clinic sites from 1 January 2004 through 31 March 2020. Diagnosis was established by culture, histopathology/cytopathology, serology, antigen testing, or PCR. Disease was categorized as mild for patients treated in the outpatient setting, moderate for hospitalized patients who did not require intensive care, and severe for patients admitted to the intensive care unit. Logistic regression was used to evaluate risk factors for severe disease. A Cox proportional hazards model was constructed to evaluate mortality. Findings: We identified 210 patients diagnosed with blastomycosis. Mean age was 51 years (range, 6–84). Most subjects were male (71.0%). Extrapulmonary disease was confirmed in 24.8%. In this cohort, 40.5% of patients had mild disease, 37.6% had moderate disease, and 21.9% had severe disease. Independent risk factors for severe disease were neutrophilia (odds ratio (OR) 3.35 (95% CI 1.53–7.35), p = 0.002) and lymphopenia (OR 3.34 (95% CI 1.59–7.03), p = 0.001). Mortality at 90 days was 11.9%. Median time from diagnosis to death was 23 days (interquartile range 8–31 days). Independent risk factors for mortality were age (OR 1.04 (95% CI 1.01–1.08), p = 0.009), neutrophilia (OR 2.84 (95% CI 1.04–7.76), p = 0.041), and lymphopenia (OR 4.50 (95% CI 1.67–12.11), p = 0.003). Blastomyces immunodiffusion had an overall sensitivity of 39.6% (95% CI 30.1–49.8). Sensitivity was higher among those who were tested 4 weeks or longer after the onset of symptoms. Urine Blastomyces antigen had a significantly higher sensitivity of 80.8% (95% CI 68.1–89.2) compared to serology. There was a trend towards higher antigen concentration in patients with severe disease. The sensitivity of PCR from respiratory specimens was 67.6% (95% CI 50.1–85.5). Conclusion: In this cohort, we did not find an association between pharmacologic immunosuppression and disease severity. Lymphopenia at diagnosis was an independent risk factor for mortality. This simple marker may aid clinicians in determining disease prognosis.

Abstract Background Bloodstream infections (BSIs) confer an increased risk of infective endocarditis (IE) in patients with a prosthetic cardiac valve. This relationship is less well established in patients undergoing valve repair. We conducted a retrospective population-based study to determine the incidence of BSIs following valve repair and identify risk factors associated with the development of IE. Methods The Rochester Epidemiology Project (REP) data linkage system was used to identify all persons who underwent valve repair in a 7-county region in Southeastern Minnesota between January 1, 2010 and December 31, 2018. Medical records were screened for the development of a BSI from time of procedure until May 15, 2020. Patients were classified as having BSI only, BSI with IE at outset, or BSI with subsequent development of new IE. IE at outset was defined as cases where IE was diagnosed at the time of initial positive blood culture. Results A total of 387 patients underwent valve repair surgery. A total of 31 (8%) patients subsequently developed a BSI, 4% within one year of surgery. Seventeen patients underwent mitral repair with annuloplasty, 9 underwent tricuspid annuloplasty, and 5 had concurrent repairs. Median time to the development of BSI was 338 days. Of the 31 patients with BSI, 4 (13%) had BSI with IE at outset. No patients developed IE subsequent to BSI, Enterococcus spp. was responsible for 3 cases of IE, and MSSA for 1. All cases occurred within one year of surgery. Given the low incidence, statistical analysis of associated risk factors for IE was not feasible. All patients with BSI and IE at outset, however, died by the end of the study period, versus 11/27 in the BSI only group. Conclusion Incidence of BSIs was higher in patients undergoing cardiac valve repair than in the general population. The incidence of IE with a BSI was 13%, which is lower than what has been previously published. It is notable that all cases of IE occurred within one year of surgery. Recognizing that endothelialization of device surfaces occurs, it is tempting to speculate that the risk of IE may be time dependent and may decline over time. Subsequent investigation of this theory is underway. Disclosures Larry M. Baddour, MD, Boston Scientific (Consultant)

Abstract Background Blastomycosis has historically been a difficult diagnosis to establish, often initially misdiagnosed as bacterial pneumonia. Serologic assays and polymerase chain reaction (PCR) tests are available, but their performance is not well defined. The objective of this study was to characterize their performance. Methods Subjects were identified via chart review of patients diagnosed with blastomycosis from 2005 to 2020. A definitive diagnosis was based on fungal culture, histopathology, or cytology. Performance characteristics of the Blastomyces antibody enzyme linked immunosorbent assay (ELISA), immunodiffusion (ID), complement fixation (CF), urine and serum antigen ELISAs, and PCR were evaluated in patients with confirmed blastomycosis. Data on patient demographics, location of disease, and mortality was also collected. Results We identified 193 patients with blastomycosis. The mean age was 51.8 years (range, 11-84) and 73.6% of patients were male. 42.5% resided in Minnesota, 18.1% in Wisconsin, and 12.9% in Iowa. Diagnosis was based on culture in 142 (73.2%) or histopathology/cytology in 67 (34.7%) patients. Granulomatous inflammation was present in 73.1% (38/52) while 21.2% (41/193) had evidence of extrapulmonary dissemination. The antibody, ID, and CF assays were positive in 43.5% (37/85), 35.1% (33/94) and 20.5% (8/39) of patients, respectively. Sensitivity of Blastomyces PCR was 40% (4/10) in sputum and 75% (21/28) in bronchoalveolar lavage (BAL) fluid. Blastomyces urine and serum antigen tests were positive in 68% (34/50) and 50% (9/18) of cases, respectively, while the urine antigen was positive in 63.6% (7/11) of disseminated cases. Patients had a positive Histoplasma urine antigen test in 54.1% (20/37) and Aspergillus galactomannan in BAL in 34.8% (8/23) of cases. Serum beta-D-glucan test was positive in 16.7% (2/12). 90-day mortality was 21/193 (10.9%) and median time from diagnosis to death was 18 days. Conclusion In this cohort, Blastomyces urine antigen was the most sensitive noninvasive test, with similar performance in pulmonary and disseminated disease. However, its utility is limited by poor specificity due to cross-reactivity. Blastomyces PCR from BAL fluid demonstrated the highest sensitivity. Blastomyces antibody, ID, and CF had poor sensitivity. Disclosures All Authors: No reported disclosures

Abstract Background Transcatheter aortic valve replacement (TAVR) was initially approved as an alternative to surgery for patients at high surgical risk. However, it is now being considered for patients with intermediate and low surgical risk. This will result in the expansion of patient pool for TAVR; hence it is of interest to ascertain risk of blood stream infection (BSI) and infective endocarditis (IE) following TAVR. We aim to study the incidence, epidemiology and risk factors associated with IE in patients who underwent TAVR and subsequently developed a BSI. Methods A population-based study was conducted in 7 counties in southeastern Minnesota using the expanded Rochester Epidemiology Project (E-REP) for all adult (≥18 years) patients who underwent TAVR from January 1st, 2010 to December 31st, 2018. Transcatheter procedures that included replacement of either the aortic or mitral valve were included. Medical records were screened for development of BSI from time of TAVR until May 15th, 2020. Patients were classified as having BSI only, BSI with IE at outset, or BSI with subsequent development of new IE. ‘Early’ IE was defined as that occurring < 12 months following TAVR, with subsequent cases defined as ‘late’ IE. Results A total of 247 patients underwent TAVR during the study period. There were 24 patients with of BSI and 10 (42%) developed IE with an annual incidence of 5 per 1000 persons-years. Median age for patients who developed IE was 85.4 years. Male gender was affected predominantly (70%). Six developed IE at outset of BSI, while four developed IE subsequent to IE. The median time to development of IE was 791 days following TAVR. There was an equal number of early and late IE cases (n=5). The most common pathogen causing IE was viridians group streptococci (n=4) followed by enterococci and coagulase-negative staphylococci with 2 patients each. Mean Charlson comorbidity index was 6.6. Two patients with IE died before resolution of infection (20%). Conclusion The incidence of BSI and subsequent IE in patients with TAVR was low in our population. Due to the small number of BSI and IE cases, statistical analysis was not feasible. An analysis of all cases seen at Mayo Clinic is planned since the number of cases would be much higher to investigate potential risk factors associated with BSI and IE. Disclosures Larry M. Baddour, MD, Boston Scientific (Consultant) M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)