2026 Southeastern Residency Conference

Linezolid as Empiric Therapy for Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: A Retrospective Cohort Analysis of Clinical Outcomes  
Katherine Albus, Kellee Geren, Samantha Walker, Brandon Hawkins 
The University of Tennessee Medical Center, Knoxville, TN 
 
Background/Purpose: Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most difficult-to-treat Staphylococcus species worldwide, with mortality exceeding 20%. Vancomycin (VAN) or daptomycin (DAP) are considered first-line empiric therapies for MRSA bacteremia.  Small subgroup analyses have suggested improved survival and faster bacteremia clearance with linezolid (LZD) versus glycopeptides, yet its role is largely unclear. This study aimed to compare the effectiveness of LZD versus VAN or DAP in patients with MRSA bacteremia.   
 
Methodology: This single-center, retrospective, observational cohort study included hospitalized between December 2017 and June 2024. The primary outcome was a composite of 60-day all-cause mortality and bacteremia persisting greater than 7 days. Secondary outcomes included the individual components of the composite outcome, duration of antimicrobial therapy, duration of bacteremia, and ICU admission. Eligible patients were 18 years of age or older, had at least one MRSA-positive blood culture, and received empiric LZD, VAN, or DAP for at least 48 hours from culture collection. VAN and DAP were assessed as composite groups. Exclusion criteria included death or transition to hospice within 48 hours of culture collection, failure to receive a study antibiotic within 3 hours of culture, receipt of a comparator antimicrobial for more than 24 hours, or lack of susceptibility to the empiric agent. 
 
Results: There was no difference in patients receiving LZD or VAN/DAP in the primary composite outcome (0% LZD vs. 43.8% VAN/DAP; P = 0.074) or the individual components of 60-day all-cause mortality (0%  LZD vs. 19.8%  VAN/DAP; P = 0.580) and persistent bacteremia greater than 7 days (0% LZD vs. 32.6% VAN/DAP; P = 0.319). The median duration of antimicrobial therapy was numerically shorter in the LZD group compared with the VAN/DAP group (19.5 days vs. 43 days, respectively), though this was not significant (P = 0.143). ICU admission rates during treatment were comparable between groups (20% LZD vs. 38% VAN/DAP; P = 0.646). The duration of bacteremia was significantly shorter among patients treated with LZD compared to VAN/DAP, with median durations of 2.4 days and 5.5 days, respectively (P = 0.036). 
 
Conclusions: In a small sample, empiric LZD for MRSA bacteremia demonstrated comparable rates of 60-day mortality and persistent bacteremia compared with VAN or DAP. LZD demonstrated a significantly shorter duration of bacteremia than VAN/DAP, although these findings may be due to LZD use in less complicated infections. These results, when considered alongside existing clinical and pharmacologic evidence, support further investigation of LZD as a potential first-line option for MRSA bacteremia. Larger, prospective studies are needed to better define the role of LZD in uncomplicated, Gram positive infections with Gram negative coverage where appropriate.  

Link: https://docs.google.com/document/d/e/2PACX-1vQzRhZffUvSQUgtz-e88XOkxVPWlCJON2KHAtHhLXttKCpq05YARaPn9673tC8gAzP64x3Ss3WU3wYN/pub