Emerging resistance in staphylococci following long-term dalbavancin treatment for prosthetic joint infections

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BACKGROUND AND OBJECTIVES: Dalbavancin, a lipoglycopeptide with a half-life of 150-200 h, is a promising treatment option for prosthetic joint infections (PJIs) and other orthopaedic implant-associated infections (IAIs) caused by multidrug-resistant staphylococci. However, in vitro studies have shown that when exposed to low concentrations of dalbavancin, staphylococcal strains resistant to dalbavancin can emerge, potentially affecting its effectiveness in cases of recurrent infection. To investigate whether dalbavancin-resistant staphylococci emerge in vivo following long-term dalbavancin treatment for PJIs or orthopaedic IAIs. PATIENTS AND METHODS: Nineteen patients who had received long-term dalbavancin treatment (≥12 weeks) following PJI or orthopaedic IAI and 25 control patients scheduled for elective prosthetic joint surgery were sampled from the nares and perineum. Each sample was subcultured on Mueller-Hinton II agar plates containing various concentrations of dalbavancin (0.0, 0.125, 0.5, and 2.0 mg/L). The growth of staphylococcal colonies was analysed using MALDI-TOF, and the MIC values of dalbavancin were determined using the gradient test method. RESULTS: Among dalbavancin-treated patients, 4 out of 19 displayed staphylococcal species resistant to dalbavancin (MIC value >0.25 mg/L according to EUCAST breakpoint tables). These four were all Staphylococcus epidermidis isolates, three from the nares and one from the perineum, and displayed MIC values of 0.38, 0.38, 0.5, and 0.75 mg/L. No resistant staphylococci were detected in the samples from the control group (P = 0.029, Fisher's exact test). CONCLUSIONS: The present study demonstrated the emergence of dalbavancin-resistant staphylococci following long-term treatment.