Daptomycin-resistant Enterococcus faecium (DRE) poses an increasing therapeutic challenge, particularly in immunocompromised patients and solid organ transplant recipients. Surveillance data from the Centers for Disease Control and Prevention indicate that approximately 6.5% of E. faecium isolates are daptomycin-resistant, underscoring the need for heightened clinical vigilance, particularly for prompt identification and treatment. In this case series, three patients with advanced liver disease, including two status post orthotopic liver transplantation, are described who developed DRE during treatment for bloodstream infection. These cases illustrate the dynamic nature of antimicrobial susceptibility under daptomycin exposure and highlight the contributions of persistent source control issues, intravascular infection, and altered host factors to treatment failure. All patients were successfully managed by escalating to combination therapy with high-dose daptomycin and ceftaroline, alongside appropriate source control. This series emphasizes the importance of periodic susceptibility reassessment during daptomycin therapy and cautions clinicians against assuming sustained susceptibility in patients with prolonged bacteremia or complex infections. Early recognition of evolving resistance and timely therapeutic adjustment may improve outcomes in this high-risk population.

Background: Heart failure with reduced ejection fraction (HFrEF) is a growing health concern, with an increased risk of thromboembolic events. Oral anticoagulants (OACs) are commonly used in HFrEF patients with atrial fibrillation, but their role in patients with sinus rhythm is unclear. Objective: To assess the safety and efficacy of OACs in HFrEF patients with sinus rhythm. Methods: A systematic review of seven studies involving 17 051 patients was conducted. Outcomes included mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization rates. Results: OACs significantly reduced non-fatal strokes compared to antiplatelets and placebo. A measurable reduction in nonfatal MIs was observed in most studies. However, no conclusive benefit was found regarding all-cause fatality and rehospitalization rates. The benefit of OACs in stroke prevention was counterbalanced by an increased risk of major bleeding episodes. Conclusion: OACs may have a role in reducing nonfatal cardiovascular events in HFrEF patients with sinus rhythm, particularly those with ischemic etiologies or underlying thrombotic states. However, further research is needed to establish their efficacy and safety in this population.