Long-term dalbavancin treatment linked to emergence of resistant *Staphylococcus epidermidis* in PJI patients

Periprosthetic joint infection (PJI) is a severe complication of joint arthroplasty, often involving multidrug-resistant staphylococci and biofilm formation, making treatment challenging. Dalbavancin, a lipoglycopeptide with a prolonged half-life, offers a promising alternative to extended intravenous therapy for these orthopaedic implant-associated infections (IAIs). However, in vitro studies have raised concerns about the potential for dalbavancin-resistant staphylococcal strains to emerge under low drug concentrations, which could compromise its long-term efficacy and contribute to recurrent infections. This study investigates this in vivo emergence.

Researchers conducted an observational study involving 19 patients who received long-term dalbavancin treatment (≥12 weeks) for prosthetic joint infections (PJIs) or other orthopaedic IAIs. A control group of 25 patients undergoing elective prosthetic joint surgery was also included. Nares and perineum samples were collected from all participants. Each sample was subcultured on Mueller-Hinton II agar plates containing varying concentrations of dalbavancin (0.0, 0.125, 0.5, and 2.0 mg/L). Staphylococcal colony growth was identified using MALDI-TOF, and dalbavancin minimum inhibitory concentration (MIC) values were determined via the gradient test method.

Among the 19 dalbavancin-treated patients, 4 (representing 21%) exhibited staphylococcal species resistant to dalbavancin, defined by an MIC value >0.25 mg/L according to EUCAST breakpoints.

These four resistant isolates were exclusively Staphylococcus epidermidis, with three originating from nares samples and one from the perineum, displaying MIC values of 0.38, 0.38, 0.5, and 0.75 mg/L. In stark contrast, no dalbavancin-resistant staphylococci were detected in any samples collected from the 25 control group patients, a statistically significant difference (P=0.029, Fisher's exact test). This finding directly demonstrates the in vivo emergence of dalbavancin resistance following prolonged exposure.