Linezolid Restrictions Linked to Lower Resistance but Higher Mortality in VRE-Screen-Positive Patients

Researchers evaluated linezolid restriction policies using electronic health records from 521,493 admissions at two academic medical centers between 2008 and 2019. The difference-in-differences study compared a hospital that introduced a prior-authorization pager system in 2011 and stricter linezolid-specific criteria with enhanced post-prescription review in 2014 against a control hospital. Outcomes included antibiotic use, linezolid resistance, in-hospital mortality by vancomycin-resistant Enterococcus (VRE) status, and stewardship request behavior.

Linezolid was used in 2.3% of admissions, and 1.2% of Enterococcus isolates were linezolid resistant. Restrictions were associated with a 27% reduction in use, an absolute decrease of 0.9 percentage points (95% CI, 0.7–1.1), and a 41% reduction in resistance, an absolute decrease of 1.0 percentage point (95% CI, 0.4–1.6). Overall mortality did not increase. However, mortality among VRE-screen-positive patients increased by 4.7 percentage points (95% CI, 1.9–7.5), with larger increases among those with bacteremia or sepsis. Approval rates declined before the number of linezolid requests fell.

These findings suggest that restriction policies may require screening-informed safeguards to preserve timely treatment for high-risk patients. The nonrandomized, two-center design limits causal interpretation and generalizability. Only the abstract was available; it does not establish whether treatment delays explained the mortality association.