Evaluation of Changes in Staphylococcus and Enterococcus Resistance Following Reduced Restrictions on Daptomycin and Linezolid

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ID: 326272
2026
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Abstract
Abstract Background Daptomycin and linezolid may have more favorable safety and efficacy profiles compared to vancomycin and require less therapeutic monitoring. To capitalize on these advantages, the University of Colorado Hospital relaxed prescribing restrictions and updated local guidance for the treatment of Gram-positive infections, resulting in increased daptomycin and linezolid utilization. The objective of this study was to assess the impact of liberalized daptomycin and linezolid use on minimum inhibitory concentrations (MICs) in Gram-positive organisms. Methods This retrospective, single-center study included all Staphylococcus and Enterococcus isolates across an 8-year period, including a 3-year follow-up period after implementing practice changes. Organisms were categorized as hospital-acquired (HA) if the culture was collected 48 hours after admission. Interrupted time series analyses were performed to measure changes in geometric mean (GM) of MICs before and after implementation. Results MICs from 19,160 isolates were evaluated, of which 7,224 were HA. Linezolid use increased to 43.7 days of therapy per 1000 patient days (DOT/1000PD) and daptomycin use increased to 15.7 DOT/1000PD post-implementation. Linezolid GM MICs trended downward pre-implementation and the trajectory was unaffected by implementation except in coagulase-negative Staphylococcus (CoNS). Daptomycin GM MICs declined pre-implementation among Enterococcus, but not Staphylococcus. Implementation was associated with a significant slope change in vancomycin-resistant Enterococcus (VRE) and HA CoNS. Resistance rates and MIC distributions were not impacted by implementation. Conclusions The liberalization of daptomycin and linezolid did not result in clinically relevant increases in resistance. Further studies are needed to confirm the durability of these results, specifically among CoNS and VRE.
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Authors Blake A Jennewein, Karrine Brade, Meghan N. Jeffres, Garth Wright, Douglas N. Fish
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Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag523
URL
https://doi.org/10.1093/ofid/ofag523
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