Increased use of daptomycin and linezolid following changes to prescribing practices at a large academic medical center was not associated with clinically relevant increases in Staphylococcus or Enterococcus resistance, according to a study published in Open Forum Infectious Diseases.

The retrospective, single-center study evaluated 19,160 Staphylococcus and Enterococcus isolates collected at University of Colorado Hospital between January 2016 and April 2024. The analysis included a 3-year follow-up period after the institution updated treatment guidance and relaxed prescribing restrictions for daptomycin and linezolid.

The study was led by Blake A. Jennewein, PharmD, who was affiliated with the University of Colorado Hospital and the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences at the time of the study.

Before the changes, the hospital generally favored vancomycin for empiric and definitive treatment of resistant gram-positive infections, while daptomycin and linezolid required approval from infectious diseases or antimicrobial stewardship services. Beginning in 2019, the hospital updated its treatment guidance and relaxed restrictions on both agents. Linezolid became the preferred anti-MRSA agent for certain skin, soft-tissue, and respiratory tract infections, while daptomycin was later recommended as first-line definitive therapy for Staphylococcus bloodstream infections. The authors referred to the combined changes as “liberalization.”

Following the changes, linezolid use increased from 4.6 to 43.7 days of therapy per 1,000 patient-days, and daptomycin use increased from 7.6 to 15.7 days of therapy per 1,000 patient-days. The researchers used interrupted time-series analyses to assess changes in minimum inhibitory concentrations (MICs) before and after the practice updates.

“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,” the authors wrote.

The analysis found no increases in S. aureus MICs after implementation. However, daptomycin and linezolid MICs increased among hospital-acquired coagulase-negative staphylococci (CoNS), and daptomycin MICs increased among hospital-acquired vancomycin-resistant enterococci (VRE). The authors reported that these changes did not result in clinically relevant increases in overall Staphylococcus or Enterococcus resistance rates.

“Resistance to daptomycin and linezolid was rare in this study,” the authors wrote, reporting that less than 1% of all isolates were resistant to either agent under 2024 Clinical and Laboratory Standards Institute breakpoints.

The authors cautioned that the study was retrospective and conducted at a single hospital, potentially limiting its generalizability. Other limitations included the absence of analyses stratified by specimen source and the relatively short observation period following increased daptomycin and linezolid use. The authors said prospective studies and longer follow-up are needed to validate the findings and assess whether resistance patterns change over time.

“The liberalization of daptomycin and linezolid did not result in clinically relevant increases in resistance,” the authors concluded, adding that further studies are needed to confirm the durability of the findings, particularly among CoNS and VRE.

The study received no financial support from public, commercial or nonprofit funding agencies. The authors reported no potential conflicts of interest.