Dyal, Natasha P.

ABSTRACT Biofilm‐associated staphylococcal infections remain exceptionally difficult to treat due to the presence of resilient staphylococcal biofilms and the limited effectiveness of currently available antibiotics. To combat persistent infections, providers are often forced to use prolonged courses of combination antimicrobial therapies that have significant toxicities with limited effectiveness, leading to increased hospital stays, substantial health care costs and a rise in patient morbidity and mortality. Staphylococcus aureus is a dominant cause of recalcitrant biofilms, for which novel non‐antibiotic therapeutics are critically needed. Lysins, a class of protein‐based antimicrobials, rapidly kill staphylococci, exhibit potent anti‐biofilm activity, have a low propensity of resistance development and synergy with antibiotics. To address this unmet need, we evaluate an extracellular vesicle (EV)‐based delivery platform for the engineered anti‐staphylococcal lysin LYSG101, designed to improve stability and localization at sites of infection. Initial proof‐of‐concept work is provided here, demonstrating that human serum‐derived EVs can be loaded with LYSG101 to exert a potent in vitro antimicrobial effect against both planktonic and biofilm forms of S. aureus . EV‐mediated delivery achieved activity equivalent to free lysin, with additional translational advantages including stability and the potential for sustained intra‐articular retention. This work supports further development of the EV‐mediated lysin delivery as a broadly applicable antimicrobial platform, with potential future applications in biofilm‐associated infections, including prosthetic joint infection (PJI).

ABSTRACT Background Strongyloides stercoralis is an intestinal parasitic nematode that can infect humans with a 2%–7% prevalence in the United States. Immunosuppression is a crucial risk factor for disseminated infection. Diagnosis is often delayed and targeted treatment is frequently initiated late. We therefore sought to review the prevalence of positive Strongyloides antibody results and undertook a descriptive analysis of such patients. Methods We retrospectively reviewed patients with positive Strongyloides IgG serology from August 2012 to April 2023 across geographically distinct academic medical centers. Study period pre‐dated universal donor and recipient Strongyloides screening recommendation by the Organ Procurement and transplantation network (OPTN). Clinical presentation was classified into three categories: chronic infection (positive Strongyloides IgG serology without additional clinical manifestations), hyperinfection syndrome (positive serology with involvement of the skin, gastrointestinal tract, or lungs), and disseminated infection (positive serology with involvement beyond those typically involved in hyperinfection). Results A total of 412 patients were identified; median age was 59 years and 66% (272) were male. The primary indication for testing was pretransplant evaluation in 230 (56%), eosinophilia workup in 84 (20%), suspicion of symptomatic infection in 74 (18%), testing based on travel history in 27 (7%), and pre‐immunosuppression screening in 27 (7%). Furthermore, 401 patients (97.3%) were categorized as having chronic infection, 10 patients (2.42%) had hyperinfection, and one patient (0.24%) had disseminated infection, presenting with Escherichia coli bacteremia and meningitis. Symptomatic infection was more common at the Mayo Clinic in Rochester and Mayo Clinic Health Sciences than at the Arizona and Florida Mayo Clinic sites (6% vs. 2%, p = 0.079). Treatment was administered to 366/412 (89%) patients. Conclusion Most patients with positive Strongyloides serology were asymptomatic, and treatment regimens were not uniform. Patients who tested positive should be treated prior to immunosuppression initiation, though this was not systematically assessed in this cohort. The observed variability in treatment regimens highlights the need for standardized protocols.