Antimicrobial Stewardship in Vancomycin-Resistant Enterococcus faecalis: Clinical Study Evaluating Antimicrobial Susceptibility Patterns and Antibacterial Regimens

Background: Vancomycin-resistant enterococci (VRE) Enterococcus faecalis (E. faecalis) remains largely ampicillin-susceptible, yet broad-spectrum agents are frequently used empirically (i.e., daptomycin and linezolid). Despite its frequent susceptibility to ampicillin, VRE E. faecalis is often managed with broad-spectrum antimicrobials, raising concerns about overtreatment and antimicrobial stewardship. Resistance mechanisms vary, with vancomycin resistance mediated by vanA/vanB operons and beta-lactams by altered penicillin binding proteins. These distinct mechanisms help explain why VRE E. faecalis isolates may remain susceptible to ampicillin, supporting its potential use in clinical isolates. This study aims to describe the antibacterial susceptibility results of Enterococcus faecalis VRE and assess antibiotics use in clinical settings in a tertiary medical center. Methods: This was a single-center, retrospective, descriptive study of hospitalized and outpatient adults with Enterococcus faecalis VRE isolates identified between 1 June 2018 and 15 March 2025. We excluded individuals with concomitant non-Enterococcus faecalis VRE infections and those aged <18 years. Vancomycin resistance was defined by a minimum inhibitory concentration of >32 mcg/mL per the 35th edition of the Clinical and Laboratory Standards Institution breakpoints. Results: A total of 337 patients were screened; 114 met inclusion criteria. The cohort was 54% female, 50% Black, and 48% White, with 54% having hypertension, 36% diabetes, and 19% a history of multidrug-resistant organism carriage. The most common source of infection was urinary (67%), followed by skin and soft tissue infections and bone/joint infections (11% each). All isolates were vancomycin-resistant; 82% were susceptible to ampicillin, 84% to nitrofurantoin, 61% to daptomycin, and 70% to linezolid. Antimicrobial regimens varied, with daptomycin being the most used agent (19%). No patients in the aminopenicillin group experienced 30-day mortality, whereas two patients (3%) in the non-aminopenicillin group died within 30 days. Acute kidney injury occurred in four patients (29%) in the aminopenicillin group compared with four patients (7%) in the non-aminopenicillin group, representing a significantly higher incidence in the aminopenicillin group (p = 0.037). However, myalgia, elevated creatine phosphokinase, and thrombocytopenia were more common in the non-aminopenicillin group. Conclusions: Despite higher susceptibility to ampicillin and nitrofurantoin, daptomycin was the most used agent for VRE E. faecalis infections. These findings highlight a need for improved antimicrobial stewardship and further clinical studies to guide optimal therapy.