Shah, Aditya

Abstract Alternaria spp. are dematiaceous ascomycetes that can cause opportunistic infections in immunocompromised hosts. They are challenging to identify and treat. However, optimal antifungal therapy remains undefined. We retrospectively reviewed antifungal susceptibilities (AST) of all Alternaria spp. isolates from adults at a tertiary care center between 2011 and 2025. We evaluated culture sources, minimum inhibitory concentration (MIC) and minimal effective concentration (MEC) distributions, and MIC₅₀/MIC₉₀ and MEC50/MEC90 values. Clinical characteristics, treatment measures, and outcomes of patients with clinically significant Alternaria spp. infections were described. Forty-one patients had Alternaria spp. isolated, most commonly from skin (n = 13), bone/joint (n = 5), nail (n = 3), or cornea (n = 3). Posaconazole and itraconazole demonstrated low MICs (MIC₅₀/MIC₉₀: 0.06/0.5 and 0.25/0.5 µg/mL, respectively). Voriconazole and isavuconazole showed higher MIC₅₀/MIC₉₀ (1/2 and 2/4 µg/mL). Caspofungin (0.125/0.5 µg/mL) and amphotericin B (0.25/1 µg/mL) had low MICs and MECs.s. Alternaria spp. represented clinically significant infection in 27 cases (66%); 26% were solid organ transplant recipients and 15% had hematologic malignancies. Other risk factors included preceding trauma (22%) and autoimmune disease (15%). Posaconazole was the most frequently used empiric agent (6, 32%). Following AST results, 14 patients (52%) received oral antifungal therapy; posaconazole was used in all 14. In addition, 7 patients (26%) received combination therapy with IV amphotericin B. Adjunctive surgery occurred in 14 cases (52%). Five patients (19%) died before completing therapy; Alternaria infections occurred predominantly in immunocompromised hosts and were frequently managed with posaconazole and surgery. Interpretive criteria for Alternaria spp. are needed to guide empiric and definitive therapy.

Abstract Healthcare personnel (HCP) are at risk for occupational exposure to tuberculosis. Current guidelines for managing exposed HCP are broad and resource intensive. Based on review of our internal data, we propose a risk-based stratification approach to streamline exposure follow-up testing and optimize resource utilization.

Abstract Background Candidemia can occur as a consequence of gastrointestinal (GI) injury. The mortality of candidemia is high, ranging 30-60%, even with treatment with antifungal agents. In this retrospective matched case-control study, we aimed to elucidate the medical and surgical risk factors of developing candidemia in patients who received emergency surgery for GI ischemia and/or perforation, and compare clinical outcomes in these patients with or without candidemia. Methods All patients ≥ 18 years of age who had emergency GI surgery at Mayo Clinic Rochester, MN, for the indication of GI ischemia and/or perforation between 01/01/2018 to 07/31/2024 were included. Cases were defined as patients who developed candidemia during index admission and had no alternative sources of candidemia. Controls and cases were matched 4:1 on age (± 5 years), Charlson Comorbidity Index (± 3), and year of surgery (± 2 years). The relationships between risk factors of interest and case/control were assessed using conditional logistic regression. Results Among medical risk factors, any shock requiring vasopressor (OR = 3.44, 95% CI 1.00, 11.97) or respiratory failure (OR = 8.20, 95% CI 1.04, 64.53) during hospitalization were associated with increased risk of candidemia. Among surgical risk factors, perforation in the upper GI tract was strongly associated with development of candidemia (OR = 16.99, 95% CI 2.11, 136.95) and perforation in the lower GI tract were less likely to lead to candidemia (OR = 0.06, 95% CI 0.01, 0.44). The patients who had diffuse intraabdominal contamination were more likely to develop candidemia compared to those who had no contamination or contained contamination (OR = 3.87, 95% CI 1.33, 11.25). The patients with candidemia showed signal towards higher in-hospital and 30-day mortality, and had significantly longer stay in the hospital. Conclusion Candidemia was more frequently identified in patients with shock, respiratory failure, upper GI perforation, and intra-abdominal contamination, and contributed to significant morbidity and mortality. Further analysis will include building a multivariate logistic regression model to implement prospective trial for early initiation of antifungal therapy for high-risk population. Disclosures All Authors: No reported disclosures

Abstract Background In 2019, the US performed 290,000 breast reconstructions with an estimated infection rate of 3-35%. Tissue expander infections detract from desired aesthetic effects, delay adjuvant treatments, increase morbidity and mortality, and have high recurrence rates (20-40%). Little is known about risk factors for recurrent tissue expander infections, particularly the impacts of different treatment modalities. Methods We conducted a single-center retrospective cohort study of adult women post-mastectomy who developed microbiologically-proven tissue expander infection between the period of 2017 – 2024. Outcomes including 12-month infection recurrence and risk factors for recurrence were compared between surgical versus nonoperative groups, as well as between three surgical strategies (i.e., one-stage, two-stage, explantation). Unadjusted and adjusted logistic regression models were used to assess the associations between the treatment modalities and the outcomes. Univariate models assessed the relationship between the covariates of interest and infection recurrence. Results 107 patients were included, with the majority treated with combination of antibiotics and surgical therapy (Table 1). There was no significant difference in outcomes when the operative versus antibiotics alone cohorts were compared (Table 2). The odds of infection recurrence and rehospitalization in patients who underwent two-staged exchange or explantation were significantly lower when compared with the one-staged group (Table 3). Univariate modeling found severity and radiation therapy to be numerically more common in the group experiencing recurrence, with a trend towards statistical significance (Table 4). Conclusion Our study demonstrates reduced risk of recurrent tissue expander infection with two-staged exchange or explantation, compared to one-staged exchange. Though limited by small sample size, the strengths of our study include our presentation of the real-world variability of these syndromes and their management, adjustment for infection severity and other potential confounders; and the focus on microbiologically-defined infections. Disclosures All Authors: No reported disclosures

Abstract Background Hematopoietic cell transplantation (HCT) is associated with a net state of immunosuppression to enable graft acceptance and mitigate graft-versus-host disease risk1. Most of these patients require multiple prophylactic antimicrobials to prevent opportunistic infections during the post-transplant course2, including central nervous system (CNS) infections3. Brain abscesses are a form of CNS infection with a high incidence of morbidity and mortality4 Methods We conducted a retrospective cohort study of adults diagnosed with brain abscess following HCT between January 2009 and December 2024, including patients from all Mayo Clinic sites (Arizona, Florida, and Minnesota). The study was approved by our institutional review board with a protocol number 24-011428. The data was extracted from the electronic medical records into a secure database in REDCap. Statistical analyses were conducted using R version 4.4.1 (R Foundation for Statistical Computing). Results We identified 22 patients with brain abscess diagnosis following HCT. 50% of patients had leukemia. 81.8% of them received prior chemotherapy. 16 patients had prior allogeneic HCT, and 54.5% received a myeloablative conditioning regimen (table 1). 21 patients had neuroimaging available. More than one cerebral lobe was involved in 42.9% of the cases. 14 patients had extra-axial infection, the lung being the most frequently affected organ. Nocardia accounted for 40.9% of the brain abscesses (table 2). 45.5% underwent surgical intervention, and most of our patients were treated with a combination of intravenous and oral antimicrobials, many of them followed by long-term suppression. 54.5% of the brain abscesses resolved, with a median time to resolution of 156 days. All-cause mortality was 59.1%, with a median time to death of 540 days after brain abscess diagnosis (table 3). Conclusion Although rare, brain abscess is a devastating complication of HCT, with high morbidity and mortality. The most common pathogen encountered was Nocardia species. The required treatment is usually extensive, and these patients often need long-term suppression. Further investigation is required to determine risk factors for specific pathogen infection, non-resolution, and mortality. Disclosures All Authors: No reported disclosures

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) recommends a blood culture contamination (BCC) threshold of <3%, with ≤1% considered optimal. However, there is not a standardized definition of BCC, and the effect of multiple definitions on BCC rates or what definitions laboratories use remain unknown. We surveyed 52 hospitals and analyzed 362,078 blood cultures (BCx) collected 1 September 2019 to 31 August 2021 from 62 intensive care units (ICUs) and 231 wards from 48 of these hospitals. We calculated and compared BCC rates using the College of American Pathologists (CAP) or CLSI criteria (both utilize a limited number of skin commensals to define BCC) and the comprehensive National Healthcare Safety Network (NHSN) commensal list. We characterized factors associated with BCC and related outcomes (central-line associated bloodstream infection [CLABSI] and vancomycin use). BCC, BCx positivity, and single BCx rates were monitored by 100%, 39%, and 21% of hospitals, respectively. Hospitals used CAP (65%), CLSI (17%), and NHSN (17%) criteria to define BCC. Mean BCC rate by CAP (CAP-BCC) was 1.38% for ICUs and 0.96% for wards. BCC rates remained similar by CLSI criteria but increased when using NHSN list. Sharing BCC data outside of the laboratory, measuring additional BCx quality indicators, and limiting central catheter-drawn BCx were associated with lower BCC rates. BCC was associated with higher CLABSI rates in ICUs. This study demonstrated variability in laboratory practices and opportunities to optimize BCx stewardship. IMPORTANCE Blood culture contamination (BCC) is associated with patient harm and unnecessary use of healthcare resources. BCC thresholds have been established; however, multiple BCC definitions exist. There is limited data on how BCC rates differ depending on the BCC definition used, what definitions laboratories most commonly use, or their approach to other blood cultures (BCx) quality indicators such as single rates or BCx positivity. A cross-sectional multicenter survey and analysis of BCx data from intensive care unit and wards revealed that most laboratories did not track single BCx or BCx positivity rates and that there was variability in how BCC was defined. Additionally, BCC rates were influenced by the definition used. BCC was associated with increased central-line associated bloodstream infection rates.

Abstract Objectives To compare the efficacy and safety of antibiotic lock therapy (ALT) versus catheter removal in managing central vascular catheter–associated bloodstream infection (CVC-BSI). Methods We conducted a single-centre, retrospective cohort study of adult patients treated with ALT or catheter removal for management of CVC-BSI between 2018 and 2022. The primary outcome was a composite of 90 day microbiological relapse or recurrent BSI. Secondary outcomes included 30 day mortality, CVC-associated complications and Clostridioides difficile infection (CDI). Logistic regression with propensity score-adjustment was used to evaluate differences in outcomes and identify predictors of relapse. Results During the study period, 106 participants received ALT and 181 underwent catheter removal. Patients treated with ALT received shorter courses of systemic antimicrobials (11 versus 14 days; P &lt; 0.001) and had shorter hospital stays (4 versus 10 days; P &lt; 0.001). Median duration of catheter salvage in patients receiving ALT was 28 days (IQR 7–80). Primary composite outcome was similar between both groups, but ALT was associated with a significantly higher risk of microbiological relapse within 90 days (20% versus 7%; adjusted odds ratio 3.93, 95% CI 1.64–9.40; P = 0.002). No significant difference in 30 day mortality, CVC-related complications or CDI was observed. CoNS BSI was an independent predictor of microbiological relapse in patients treated with ALT (OR 2.28; P = 0.05). Conclusions Although ALT offers a non-invasive catheter salvage strategy, its association with higher relapse rates, particularly in CoNS BSI, suggests catheter removal should remain the preferred approach when feasible. ALT could be considered a short-term catheter salvage strategy for pathogens with low virulence when used with close surveillance.

Abstract Objective: To retrospectively observe procalcitonin (PCT) and antibiotic ordering practices in patients hospitalized with community-acquired pneumonia (CAP). Design: Retrospective, exact matched, multicenter cohort study from October 1, 2018 – March 31, 2023. Setting: All hospitals across the Mayo Clinic Enterprise. Participants: Adult patients with CAP, identified using pneumonia diagnosis codes and receipt of systemic antibiotics with an indication of “respiratory tract infection” within 48 hours of hospitalization. Methods: PCT testing within the first 7 days of hospitalization was compared to non-PCT care (nPCT). The primary outcomes were treatment duration, antibiotic days of therapy (DOT), and length of stay (LOS). Results: 15364 patients met inclusion criteria. PCT testing occurred in 42.4% (6515/15364) of encounters, totaling 8214 PCT results. 12880 unique patient encounters were matched 1:1, 6440 in each group. Treatment duration was longer in the PCT group compared to the nPCT group (5.1 vs 4.6 days, respectively, P < 0.001). Patients in the PCT group also received more DOT (8.6 vs 7.6 DOT, P < 0.001) and had a longer LOS (6.8 vs 5.9 days, P < 0.001), respectively. There was no difference in 30-day all-cause mortality or C. difficile infection between groups. In a sensitivity analysis of nPCT patients compared to those with a peak value <0.25 ng/mL (i.e. normal result) there was no difference in treatment duration (4.6 days nPCT vs 4.7 days normal PCT, P = 0.104) or LOS (5.9 days nPCT vs 6.0 days normal PCT, P = 0.134). Conclusion: PCT testing in patients hospitalized with CAP was not associated with reduced antimicrobial utilization, LOS, or 30-day all-cause mortality.

ImportanceBlood culture (BC) use benchmarks in US hospitals have not been defined.ObjectiveTo characterize BC use in adult intensive care units (ICUs) and wards in US hospitals.Design, Setting, and ParticipantsA retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted. Critical access hospitals, less than 6 months of BC data, and non-US hospitals were excluded. The study included BC use data from September 1, 2019, to August 31, 2021. Data were analyzed from February 23 to July 14, 2024.Main Outcomes and MeasuresThe primary outcome was BC use per 1000 patient-days. Adjusted means with 95% CIs were calculated using mixed-effects negative binomial regression models adjusted for unit type, hospital bed size, geographic region, seasonality, and state COVID-19 case load, with random intercepts accounting for clustering at unit and hospital levels. Secondary outcomes included blood culture positivity, single BCs, BC contamination, and minimum threshold for BC use where blood culture positivity would be optimized.ResultsA total of 362 327 blood cultures were analyzed from 27 medical ICUs, 35 medical-surgical ICUs, 121 medical wards, and 109 medical-surgical wards from 48 hospitals in 19 states and the District of Columbia. The adjusted mean BC use per 1000 patient-days was 273.1 (95% CI, 270.2-275.9) for medical ICUs, 146.0 (95% CI, 144.5-147.5) for medical-surgical ICUs, 80.3 (95% CI, 79.8-80.7) for medical wards, and 65.1 for medical-surgical wards. Blood culture use was significantly higher across all 4 unit types in hospitals with more than 500 beds compared with 500 or less beds and in the West-Midwest compared with other regions. Single blood culture and positive blood culture rates were below 10% across all 4 unit types. Of the 292 units, 97% had a mean BC contamination rate within 3% of the recommended threshold, and 51% were within 1%. The minimum BC use thresholds (ie, BC use below this number may represent undertesting) were 120 BCs per 1000 patient-days for medical ICUs, 80 BCs per 1000 patient-days for medical-surgical ICUs, and 30 BCs per 1000 patient-days for medical-surgical wards.Conclusions and RelevanceThe findings of this study suggest that blood culture positivity may help determine appropriate BC use for individual unit types.