Comparative efficacy of dalbavancin alone and with rifampicin against in vitro biofilms in a pharmacodynamic model with methicillin-resistant Staphylococcus aureus

•In vitro PK/PD biofilm model was used to compare Dalbavancin efficacy against MRSA•Dalbavancin (DAL) monotherapy showed similar activity than vancomycin•The addition of rifampicin improved the activity of DAL against both MRSA strains•No DAL resistance appeared over time either in monotherapy or in combination The anti-biofilm efficacy of dalbavancin has been evaluated in static models. Using an in vitro pharmacokinetic/pharmacodynamic model, we evaluated the comparative activity of dalbavancin alone and with rifampicin against biofilm-embedded methicillin-resistant S. aureus (MRSA). Two MRSA strains (HUB-4/HUB-5) were evaluated with the Calgary Device System and the dynamic CDC-Biofilm Reactor over 144 h. Dosage regimens simulated the human pharmacokinetics of dalbavancin (1500mg, single dose), vancomycin (1000mg/12 h) and linezolid (600mg/12 h), alone and with rifampicin (600mg/24 h). Efficacy was evaluated by assessing log10 CFU/mL changes (ΔlogCFU/mL) and we screened for resistance. The minimal biofilm inhibitory/eradication concentrations of dalbavancin were 0.25/16 mg/L (HUB-4) and 0.25/8mg/L (HUB-5), respectively. In the pharmacokinetic/pharmacodynamic analysis, dalbavancin alone showed limited efficacy, but without resistance developing. Adding rifampicin improved the activities of dalbavancin, vancomycin, and linezolid, but rifampicin-resistant strains appeared over time in all cases. Dalbavancin-rifampicin was bactericidal against HUB-4 in the absence of resistance at 72 h and 144 h (ΔlogCFU/mL: −3.54±0.83, −4.32±0.12, respectively), an effect that was only achieved by linezolid-rifampicin at 144h (-3.33 ± 0.66). Against HUB-5, dalbavancin-rifampicin activity was impaired by rifampicin resistance to a greater extent than other combinations and had no bactericidal effect. The anti-biofilm efficacy of dalbavancin was improved significantly by adding rifampicin. Although no dalbavancin resistance occurred, rifampicin resistance appeared in all combination therapies and decreased their efficacy over time. Dalbavancin-rifampicin in vitro treatment appears as promising anti-biofilm therapy, but further studies should evaluate the in vivo efficacy and the risk of resistance.