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

Area of Science:

• Infectious Diseases
• Microbiology
• Pharmacology

Background:

• Dalbavancin is a lipoglycopeptide effective against multidrug-resistant staphylococci in prosthetic joint infections (PJIs) and orthopaedic implant-associated infections (IAIs).
• In vitro studies suggest dalbavancin resistance can emerge in staphylococci exposed to low drug concentrations, raising concerns for recurrent infections.
• The in vivo emergence of dalbavancin resistance following long-term treatment for PJIs/IAIs remains under investigation.

Purpose of the Study:

• To investigate the in vivo emergence of dalbavancin-resistant staphylococci in patients undergoing long-term dalbavancin treatment for PJIs or IAIs.
• To compare the prevalence of resistant staphylococci in treated patients versus a control group.

Main Methods:

• Nineteen patients with PJIs/IAIs treated with dalbavancin (≥12 weeks) and 25 control patients were sampled from nares and perineum.
• Staphylococcal isolates were cultured on agar with varying dalbavancin concentrations.
• Isolates were identified using MALDI-TOF, and minimum inhibitory concentrations (MICs) were determined via gradient testing.

Main Results:

• Dalbavancin-resistant staphylococci were detected in 4 out of 19 (21%) treated patients (MIC >0.25 mg/L).
• All resistant isolates were Staphylococcus epidermidis, with MIC values ranging from 0.38 to 0.75 mg/L.
• No resistant staphylococci were found in the 25 control patients (P=0.029).

Conclusions:

• Long-term dalbavancin treatment is associated with the emergence of dalbavancin-resistant staphylococci in vivo.
• The findings highlight a potential clinical challenge for dalbavancin's efficacy in managing recurrent PJIs/IAIs caused by staphylococci.