TOPLINE

Liberalizing daptomycin and linezolid use at a large academic medical center did not result in clinically significant increases in resistance rates among Staphylococcus and Enterococcus species over an 8-year period. Despite higher use of both agents, minimum inhibitory concentrations (MICs) for methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus species remained stable or declined, and resistance was rare.

METHODOLOGY

• Researchers conducted a retrospective analysis of 19,160 Staphylococcus and Enterococcus isolates collected from January 2016 to April 2024 to assess the impact of increased utilization of daptomycin and linezolid on staphylococcal and enterococcal MICs.
• They implemented policy changes between 2019 and 2021 that relaxed prescribing restrictions and updated local guidance to favor linezolid for skin and soft tissue infections and respiratory tract infections, and daptomycin for bloodstream infections.
• Linezolid utilization increased from 4.6 to 43.7 days of therapy per 1000 patient days post-liberalization, while daptomycin use doubled from 7.6 to 15.7 days of therapy per 1000 patient days; vancomycin use declined from 97.8 to 44.4 days of therapy per 1000 patient days.
• Researchers measured changes in geometric mean MICs before and after implementation, with organisms categorized as hospital-acquired if cultures were collected ≥ 48 hours after admission.

TAKEAWAY

• Daptomycin resistance remained below 1% across all Staphylococcus groups, with geometric mean MICs and MIC90 values staying at 1 mcg/mL for S aureus and MRSA throughout the study period.
• No linezolid resistance was detected in any S aureus or MRSA isolates; geometric mean MICs declined from 1.848 to 1.251 mcg/mL in all S aureus isolates and from 1.797 to 1.193 mcg/mL in MRSA isolates.
• Among Enterococcus species, daptomycin geometric mean MICs decreased from 2.194 to 1.742 mcg/mL, with susceptibility rates exceeding 97% based on a 4 mcg/mL breakpoint; linezolid geometric mean MICs declined from 1.463 to 1.129 mcg/mL, with no vancomycin-resistant Enterococcus (VRE) isolates resistant to linezolid after liberalization.
• Statistically significant but subclinical increases in daptomycin geometric mean MICs were observed in hospital-acquired VRE (P < .01) and hospital-acquired coagulase-negative Staphylococcus (P < .01) post-liberalization.

IN PRACTICE

"Our study did not observe any concerning trends in Staphylococcus or Enterococcus resistance rates or MIC distributions over an 8-year period that included a 3-year follow-up after liberalization of daptomycin and linezolid use. Clinically relevant resistance was not prevalent in this study and increased daptomycin and linezolid utilization was not associated with increasing MICs among MRSA, Enterococcus spp., and hospital-acquired S. aureus," the authors of the study wrote.

SOURCE

The study was led by Blake A. Jennewein, PharmD, UCHealth University of Colorado Hospital, Aurora, Colorado. It was published online on August 22, 2026, in Open Forum Infectious Diseases.

LIMITATIONS

The retrospective design may have introduced bias from unaccounted confounders affecting antibiotic utilization or pathogen susceptibilities. The relatively short post-liberalization observation period may have been insufficient to detect delayed resistance emergence, as some studies report resistance increases occurring several years after increased consumption. The single-center design and exclusion of certain coagulase-negative Staphylococcus isolates from non-sterile specimens may limit generalizability.

DISCLOSURES

The study did not receive financial support from public, commercial, or not-for-profit funding agencies. The authors reported no potential conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.