Citations

Abstract Background Strongyloides stercoralis is an intestinal parasitic nematode with a 2% - 7% prevalence in the United States. Immunosuppression can predispose to disseminated infection, concurrent bacterial sepsis and significant morbidity and mortality. We sought to review positive Strongyloides serology (PSS) results across 3 academic medical centers. Methods Electronic medical records of patients with PSS were reviewed between 2012 and 2023. Extracted data included demographics, country of origin, travel history, testing indication, clinical presentation, treatment regimen and duration. Patients were classified into chronic infection (PSS without additional clinical manifestations), hyper infection syndrome (cutaneous, gastrointestinal tract, or lung involvement), and disseminated infection (evidence of involvement of distant sites beyond hyper infection such as the brain, liver, kidneys, or bloodstream). Results Overall PSS rate across the 3 sites was 5.5%. A total of 412 patients with PSS were identified with a mean age of 56.7 years (SD ±14.2); 272 (66%) were male. The primary indication for testing was transplant evaluation in 230 (56%), eosinophilia workup in 84 (20%), suspicion of active infection in 74 (18%), travel history in 27 (7%), and pre-immunosuppression screening in 27 (7%). 401 (97.3%) were categorized as chronic infection,10 (2%) as hyper infection, and one patient (0.2%) as disseminated infection. Treatment was administered to 366 (89.3%) patients: 226 (61.7%) received 2 doses of Ivermectin on consecutive days, 94 (25.7%) received a single dose, 26 (7.1%) received 2 doses repeated 2 weeks later, and 20 (5.5%) received alternative regimens. The patient with disseminated infection received 2 weeks of Ivermectin followed by monthly dosing. Conclusion Majority of the patients with PSS were asymptomatic, and treatment regimens were not uniform. Screening should be considered for patients currently receiving or initiating long-term immunosuppression that can potentiate Strongyloides dissemination. Developing a targeted testing algorithm based on epidemiologic factors, clinical suspicion, laboratory parameters and nature of immunosuppression can help identify at-risk patients who can receive pre-emptive therapy if infected. Disclosures All Authors: No reported disclosures

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) has been shown to have numerous benefits including lower costs, increased patient satisfaction, and decreased healthcare associated infections. Patient education is a crucial part of the OPAT process, as lack of understanding may lead to adverse drug events, emergency department visits, or hospital re-admission. A baseline survey of OPAT clinicians at a large multi-state health system revealed low awareness of existing OPAT education resources and consensus that the materials needed improvement. We hypothesized that an OPAT education video would improve OPAT staff satisfaction with the educational offerings.Figure 1.OPAT Video Link Engagement (2024)Figure 2.Patient Electronic Chart Message Methods Adult patients ( > 18 years of age) enrolled in OPAT programs at 4 sites within Mayo Clinic throughout Minnesota and Wisconsin from 5/1/23 - 8/1/24 were included. A standardized OPAT patient education video was developed using voice over PowerPoint slides. Video content included lab monitoring requirements, signs and symptoms of adverse effects including alarm symptoms, and intravenous catheter care. The video was available as a link for delivery via patient electronic chart message, to be played on clinic and hospital room computers, and accessed by patients via QR code on rack cards. We implemented inclusion rules built within our electronic health record which automated the delivery of these patient chart messages. The primary outcome was staff satisfaction with OPAT education materials. Secondary metrics included number of video patient accesses in hospital and clinic rooms, number of message deliveries, and frequency of message opening. Staff satisfaction with OPAT education was compared pre- and post-intervention using the Pearson chi-square test. Results The patient education video was accessed 73 times in hospital and clinic rooms and was delivered by automated patient chart message 157 times during the study period. Patient chart messages were opened 91.5% of the time. The percentage of staff who felt OPAT education materials needed improvement decreased from 90% pre-intervention to 38.1% post-intervention (p=0.05). Conclusion A standardized OPAT patient education video allowed for efficient electronic delivery of educational information to patients and improved OPAT staff satisfaction. Disclosures All Authors: No reported disclosures

Abstract Background Invasive aspergillosis (IA) remains a common cause of both direct and contributable mortality in patients with hematologic malignancies (HM). Given the advances in antifungal management, it would be important to assess IA-attributable mortality (AM) and contributable mortality (CM), in addition to overall mortality (OM). Methods We retrospectively reviewed the records of 76 consecutive HM patients with proven/probable culture-positive IA (MSG/EORTC criteria) from 2015 to 2021. Death causality was adjudicated based on published criteria. AM was defined as death “due to” IA, while CM as death “due to” and “with” IA. OM encompassed death from any cause. Mortality rates and death causalities were evaluated at 2-, 4-, 6-, and 12-week intervals following IA diagnosis. A multivariate competing risk analysis was performed to identify independent risk factors for 6-week AM, with other death causalities as the competing event. To increase diagnostic accuracy, we excluded culture-negative, Aspergillus galactomannan (GM) positive cases, as GM can be produced by other hyalohyphomycetes. Results The median patient age was 60 years (61%). Lymphoma and multiple myeloma (L/MM) were the most common HM (40, 53%). The remaining patients had active leukemia. Twenty-nine patients (38%) had prior stem cell transplantation, and 10 (13%) had graft-versus-host disease. Aspergillus fumigatus was the most common species (47%). Six and 12-week mortality rates were 18.7% and 22.7% for AM, 42.7% and 49.3% for CM, and 45.3% and 53.3% for OM, respectively. Notably, 2-week OM was 27.6%. Lack of neutrophil recovery was the only independent risk factor for 6-week AM on multivariate analysis (OR=4.2, p=0.006). Conclusion Our findings reflect the modern reality of culture-documented IA, occurring mostly in HM patients with heavily pretreated L/MM not routinely receiving mold-active prophylaxis, and in those with active leukemia. In this real-life contemporary HM population, culture-positive IA was associated with high cumulative OM and CM. Understanding AM and CM rates could lead to more accurate sample size estimations in clinical mycology trials. Such trials should be pragmatic and assess antifungal failure at an earlier time point than the traditional 4-week mark post-diagnosis. Disclosures Dimitrios P. Kontoyiannis, MD, AbbVie, Inc: Advisory Board Participation|Astellas: Grant/Research Support|Basilea: Advisor/Consultant|Cidara, Inc: Advisory Board Participation|F2G, Inc: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Knight, Inc: Honoraria|Pfizer: Advisor/Consultant|Scynexis: Advisor/Consultant|TTF Pharmaceuticals, Inc: Advisor/Consultant|US-Israel Binational Sci Foundation: Grant/Research Support

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) is effective and cost-efficient, but 12%–63% of patients experience adverse events, requiring close monitoring. Therapeutic drug monitoring (TDM) is routinely used for vancomycin and aminoglycosides but is underutilized for beta-lactams (BLs) due to limited access, logistical barriers, and clinician inexperience. This study evaluated its use and clinical impact within a high-volume OPAT program. Methods This retrospective, single-center cohort included adult patients (≥18 years) enrolled in an OPAT program who received cefepime (CEF), piperacillin/tazobactam (TZP), or meropenem (MEN) and underwent BL TDM between April 2023 and April 2025. BL TDM was not protocolized within the OPAT program; however, institutional guidance supported its use in carefully selected patients. We aimed to describe TDM indications, lab trends, microbiological profiles, and the impact of TDM on treatment. Results During the study period, 25 OPAT patients underwent BL TDM. TDM was performed in patients receiving CEF (64%), TZP (20%), and MEN (16%). The most common indication for TDM was suspected beta-lactam toxicity (32%) (Figure 1). Post-TDM therapy adjustments were made in 52% (n = 13), including changes in dosing frequency (38.5%) and dosage strength (30.8%). Additional changes included infusion strategy modification or agent substitution (15.4% each). Subtherapeutic levels were the most common reason for adjustment (46.2%), followed by adverse effects, supratherapeutic levels, and changes in renal function (23.1% each). Skin, soft tissue, and musculoskeletal infections were most common (Figure 2). Positive cultures were present in 80%, with Pseudomonas spp most frequently isolated. Therapy was completed in 17 patients; 7 discontinued early, and 1 had treatment ongoing. Reasons for therapy discontinuation are detailed in Table 1. Conclusion BL TDM is contributing to a paradigm shift in OPAT practice by improving both efficacy and safety. While inpatient TDM typically targets efficacy, safety concerns more commonly motivate TDM in the OPAT setting. Although this review involved a small cohort, our experience adds to the growing body of evidence supporting BL TDM as a tool to enhance patient outcomes in the OPAT setting. Disclosures All Authors: No reported disclosures

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) allows patients to complete extended antimicrobial treatment at home, improving quality of life and reducing healthcare costs. National guidelines outline best practices for antimicrobial administration, vascular access management, monitoring, and recommend involving an infectious disease physician and a multidisciplinary team. Evaluating adherence to these practices can identify improvement opportunities and enhance outcomes. The primary objective of this study was to assess patient outcomes related to adherence to OPAT best practices at Mayo Clinic Health System – Southwest Wisconsin (MCHS–SWWI). Secondary objectives included evaluating adherence to key process metrics and identifying associations between baseline characteristics and outcomes. Methods This retrospective cohort study included adults discharged from MCHS–SWWI on home OPAT from November 2021 to July 2024. Patients were excluded if under 18 years old or if they received OPAT in non-home settings (e.g., skilled nursing, infusion center). Data on process metrics, outcomes, and safety were collected through manual chart review. These findings were evaluated against established best practices to assess the OPAT program's adherence and determine the impact of this adherence on patient outcomes. Statistical analysis used Pearson’s chi-square tests and Wilcoxon rank sum tests to measure associations of patient characteristics with outcomes. Results A total of 164 patients were included. The MCHS-SWWI OPAT program demonstrated high adherence ( > 85%) to majority of established best practices. Successful OPAT completion occurred in 92.7% of patients, and overall incidence of adverse events and poor outcomes was generally low. Adherence to best practices was below 85% for vascular access selection (81.7%) and completion of weekly labs and vascular access care throughout the OPAT course (∼69%). Conclusion High adherence to OPAT best practices led to a generally low incidence of adverse events, treatment failures, and other unfavorable patient outcomes. The results of this study provide valuable insights to guide institutional quality improvement initiatives aimed at optimizing patient outcomes in OPAT therapy through targeted interventions. Disclosures All Authors: No reported disclosures

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) practice has continued to increase. We sought to understand current OPAT practices in a survey of U. S. clinicians.Figure 1Respondents rated their agreement with the following statement: “The OPAT program at my hospital receives adequate support in the following areas”Figure 2Factors present in providing safe OPAT services on a scale where 1 is “extremely challenging” and 5 is “not challenging at all” Methods A survey instrument was developed by ID physicians, pharmacists and Infectious Diseases Society of America (IDSA) Emerging Infections Network (EIN) staff, utilizing prior EIN OPAT surveys. The survey focused on respondents’ role, responsibilities, time devoted to OPAT, structure of OPAT provision, location where OPAT is received, institutional support and oversight, role of complex outpatient antimicrobial therapy (COpAT) including oral antimicrobials and long-acting injectable agents, and barriers to safe OPAT care. The confidential survey was distributed to adult EIN members from Feb to March 2025. Results Overall, 622 (38%) EIN members responded to the survey, of whom 469 with a role in managing OPAT patients were eligible to complete the survey. OPAT teams varied across programs with nearly all involving ID physicians (98%), majority involving ID/OPAT pharmacists (61%), nurses (60%), and nearly half involving administrative staff (48%) and advanced practice providers (APPs, 47%). ID consultation for OPAT enrollment was required in 60% of programs. Many programs (59%) report including COpAT. Response to outpatient lab results was largely managed by ID physicians (75%); however, multidisciplinary OPAT teams (37%), pharmacists (33%), and inpatient ID physicians (30%) were also frequently involved. Lab values were most often available via fax/email (43%) or electronic health record (EHR, 41%). Nearly 25% of programs “often/always” required proactive outreach to obtain safety labs. Overall, many programs lacked data analysis, administrative, information technology, and financial support (Figure 1). Challenges faced by OPAT programs included lack of leadership awareness of the value of OPAT (51%), difficulty managing patients with substance use disorder (50%), access to timely lab values (48%), personnel to retrieve missing lab values (46%), and struggles with the EHR (43%) (Figure 2). Conclusion Compared to EIN OPAT surveys in 2013 and 2019, programs have grown in size and composition, and expanded to COpAT. Similar problems persist regarding perceived lack of support. Disclosures Monica V. Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, FMSHP, gsk: Advisor/Consultant|seqirus: Advisor/Consultant Philip M. Polgreen, MD, Eli Lily: Advisor/Consultant|Pfizer: Grant/Research Support Sara C. Keller, MD, MPH, MSPH, CorMedix: Grant/Research Support

Abstract Background Within the Coccidioides-endemic area, coccidioidomycosis (cocci) has been identified as the cause of pneumonia in 15-29% of patients with community-acquired pneumonia (CAP). Although efforts to improve testing CAP patients for cocci are underway in the outpatient settings in Arizona, we do not know whether testing is common among patients admitted to the hospital with pneumonia. We undertook the current study to assess the frequency of testing for cocci among hospitalized patients with pneumonia in our institution, and to understand whether positive serologic testing led to a reduction in antibiotic use. Methods We commissioned the creation of an electronic tool by our Information Technology colleagues to create a report to identify inpatients of Mayo Clinic Hospital with a pneumonia diagnosis (J18.0 – J18.9) and information regarding testing for Coccidioides by any serology (enzyme immunoassay, immunodiffusion or complement fixation) and patient receipt of antibiotics or antifungal treatment (name, inclusive dates). Results Between January 1, 2024 and December 31, 2024, 1162 patients were admitted to the Hospital Internal Medicine service at Mayo Clinic Hospital, Phoenix AZ with a pneumonia diagnosis. Among these, 771 (66%) were tested serologically for coccidioidomycosis, and 87/771 (11%) were found to be positive. By calendar month, the percent of patients tested ranged 59 – 73%, and percent test positivity ranged 3% (March) - 19% (December). The mean time from admission to test order was 0.5 days (range 0 – 6 days) and mean time from admission to positive result was 3.0 days (range 0.4 – 12.0 days). However, among seropositive patients, the duration of antibiotics was 4.2 days, not different when compared with patients who were either seronegative or not tested, (4.1 days, p=NS). 173 (14.9%) received antifungal treatment during hospitalization, among whom 55 (31.2%) had positive coccidioidal serology and 118 (68.2%) did not. Conclusion Coccidioidomycosis is an important cause of pneumonia within the inpatient setting. However, one third of patients were not tested, representing an opportunity to understand and overcome barriers to testing. Positive tests were not associated with a reduction of antibiotic use. Disclosures All Authors: No reported disclosures

Abstract Background Detecting Histoplasma (HP) and Blastomyces (BM) antigen (Ag) in urine (U) and serum (S) is an essential diagnostic tool for these pathogens. Labs have added bronchoalveolar lavage (BAL) and cerebrospinal fluid (CSF) as additional HP and BM Ag testing sources. We evaluated the sensitivity of Ag detection in U and S in patients with detected HP or BM Ag in BAL or CSF by enzyme immunoassay (EIA). Methods 14 patients with HP or BM Ag-positive results made up the CSF cohort. The Ag concentrations were below the limit of quantification (< LoQ, N=3), above the limit of quantification ( > LoQ, N=1), and 0.3 to 9.5 ng/mL (x̄ = 2.3 ng/mL, N=10). The BM Ag-positive in BAL group included 24 patients, with concentrations of < LoQ (N=4), >LoQ (N=5), and 0.3 to 11.3 ng/mL (x̄ = 3.5 ng/mL, N=15). HP Ag-positive in BAL comprised 36 patients, with 3 < LoQ, 10 >LoQ, and 23 ranging from 0.8 to 16.9 ng/mL (x̄ = 4.7 ng/mL). 16 patients in the BAL cohorts were Ag-positive for HP and BM, demonstrating the inability to discriminate between these dimorphic fungi through Ag testing. All patients were checked for routine clinical HP and BM EIA Ag test results on U and S. HP BAL patients were also investigated for cross-reacting galactomannan (GM; Aspergillus EIA in S or BAL) and (1→3)-β-d-glucan (BDG; Fungitell EIA in S) antigen test orders. All additional test results over 14 days before or after CSF or BAL Ag testing were excluded. Results 100% (14/14), 96% (22/23), and 83% (30/36) of HP/BM CSF, BM BAL, and HP BAL Ag-positive patients were also positive in U and/or S, when both additional sources were ordered, respectively. Of the 6 HP BAL patients without positive U or S results, 3 had GM and BDG testing performed. All 3 had high signal GM and/or BDG results in S and/or BAL. In conjunction with low HP Ag levels in BAL (1.0 to 1.53), these findings suggest cross-reactivity in the HP BAL Ag test. Classifying these 3 patients as HP BAL false-positive shows a positive agreement of 91% (30/33) between HP BAL and HP U/S. Conclusion HP and BM CSF Ag testing showed no increase in sensitivity when U and S were tested. Minimal increases in sensitivity were observed in HP and BM BAL versus U and S. However, false-positive results in BAL due to cross-reactivity with GM and BDG cannot be ruled out, suggesting limited utility of the invasive CSF and BAL sources for HP and BM EIA Ag testing. Disclosures All Authors: No reported disclosures

Abstract Background Leishmaniasis is a rare protozoan parasitic disease transmitted through the bite of infected Phlebotomus and Lutzomyia sandflies. Clinical presentation is variable due to numerous species and host immunity differences. We present our clinical experiences with CL to guide timely diagnosis and treatment in returning travelers. Methods We retrospectively analyzed a cohort of adult patients 18+ years old who were diagnosed with CL from 2005 and 2025. We describe the demographic, clinical, and diagnostic features of CL. Results Biopsy-confirmed CL was diagnosed in 20 returning travelers (Table 1) from various endemic regions, most commonly Costa Rica (Fig. 1). The median time from travel to symptom onset was 36.5 days (SD 102), with an additional 75.5 days (SD 87) prior to biopsy diagnosis. All patients were evaluated by dermatology and 70% were evaluated by infectious disease (n=14). On initial presentation, lesions were described as ulcerated (50%, n=10), nodular (30%, n=6), painful (20%, n=4), and necrotic (10%, n=2; Fig. 2). Most lesions were located on the upper extremity (55%, n=11), followed by the face (35%, n=7), lower extremity (30%, n=6), and trunk (15%, n=3). 15% of individuals (n=3) had constitutional symptoms. No patients had definitive mucosal involvement, however, 10% (n=2) endorsed lip edema. No patients had visceral involvement. Species level identification occurred in 14 cases (70%), of which the most common was L.V. panamensis (50%), L.L. mexicana (21%), L. V. guyanensis (14%), L. L. tropica (7%), and L. V. braziliensis (7%). Initial treatments included azoles, liposomal amphotericin B (AmBisome), and miltefosine (each 20%); cryotherapy and parenteral pentamidine (each 10%); with compounded topical paromomycin added in 15% of cases. 35% of individuals (n=7) failed initial treatment and required additional treatment courses due to persistent lesions (57%) or relapse following initial resolution (14%). 10% (n=2) required a third treatment course due to persistent/recurrent lesions. Conclusion While CL in travelers has a variety of clinical manifestations, travel history, knowledge of key clinical features, and lesion patterns can aid in early diagnosis and treatment. CL is associated with early treatment failure rate for uncertain reasons. Disclosures All Authors: No reported disclosures

Abstract Background Pathogenesis of Scrub typhus (ST), a tick-borne acute zoonotic disease caused by the bacterium Orientia tsutsugamushi, involves infection of vascular endothelial cells, triggering a potent cytokine host response that causes organ damage. Methods Prospective study in a tertiary care hospital in North-west India in 30 cases of Scrub typhus. Measurements of cytokines IL-17A, INF-γ, TNF-α, IL-10, IL-6, IL-4, and IL-2 were carried out at admission in all 30 patients and a control group of 10 healthy persons using BDTM Cytometric Bead Array, BD Biosciences, San Diego, California, USA. Results Mean age of the entire cohort was 36 years, and the male-female ratio was 2:1. The most common symptoms were dyspnea 87%, altered sensorium 23%, abdominal pain 20%, decreased urine output 10% and myalgia in 10%. On clinical examination, eschar was present in 40%. Investigations revealed anemia in 80% cases, leukocytosis in 46.6%, thrombocytopenia in 90%, jaundice in 53.3% and elevated serum transaminase levels in 84% cases. Of all complications, acute respiratory distress syndrome occurred in 90% patients, acute kidney injury in 37% patients, acute meningoencephalitis syndrome in 30%, and myocarditis in 23%. The mean APACHE 2 score of the entire cohort was 12 . Multi-organ dysfunction syndrome (MODS) was seen in 67% of cases, and the overall mortality rate was 20%. On Fisher's Exact Correlation analysis, presentation with meningoencephalitis, myocarditis, systemic acidosis, and a high APACHE 2 score correlated with mortality. The serum levels of cytokines were elevated in all patients compared to the healthy control group (Table 1), but did not significantly differ between survivors and non-survivors. Furthermore, the elevated levels of TNF-α (p=0.004) and IL-10 (p=0.029) strongly correlated with multi-organ dysfunction syndrome (MODS). Conclusion In Scrub Typhus, the strong correlation of serum levels of TNF-α and IL-10 with multi-organ dysfunction syndrome (MODS) suggests their involvement in disease progression. The high prevalence of acute respiratory distress syndrome and MODS, alongside a mortality rate of 20%, highlights the critical nature of scrub typhus and the necessity for early recognition of complicated disease and intervention. Disclosures All Authors: No reported disclosures