Antibiotic Stewardship, Resistance, and Mortality in Vancomycin-Resistant Enterococcus: A Quasi-Experimental Study of Linezolid Restrictions

Abstract

Background Antibiotic restriction policies are intended to curb resistance, but their effects on resistance, timely treatment, and patient outcomes remain uncertain. We evaluated linezolid restrictions and whether vancomycin-resistant Enterococcus (VRE) screening identifies patients most likely to benefit. Methods We conducted a quasi-experimental difference-in-differences study using electronic health record data from 521,493 admissions at 2 academic medical centers from 2008 through 2019. Hospital 1 introduced a formal prior-authorization pager system in 2011 and stricter linezolid-specific criteria with enhanced post-prescription review in 2014; Hospital 2 served as a control. Outcomes included linezolid use, linezolid-resistant Enterococcus isolates, in-hospital mortality overall and by VRE status, and stewardship request behavior. Results Linezolid was used in 2.3% of admissions; 1.2% of Enterococcus isolates were linezolid resistant. Restriction policies were associated with a 27% reduction in linezolid use (-0.9 percentage points; 95% confidence interval, -1.1 to -0.7; P < .001) and a 41% reduction in resistance (-1.0 percentage points; 95% confidence interval, -1.6 to -0.4; P = .003). Overall mortality did not increase, but mortality among VRE-screen-positive patients increased by 4.7 percentage points (95% confidence interval, 1.9 to 7.5; P < .001), with larger increases among those with bacteremia or sepsis. Approval rates declined first, followed by fewer linezolid requests. Conclusions Restriction policies can reduce antibiotic use and resistance but may benefit from screening-informed safeguards to preserve timely treatment for high-risk patients.