In vitro activity of oritavancin in combination with rifampin or gentamicin against prosthetic joint infection-associated methicillin-resistant Staphylococcus epidermidis biofilms

Abstract

This study evaluated the in vitro activity of oritavancin in combination with rifampin or gentamicin against methicillin-resistant Staphylococcus epidermidis (MRSE) biofilms. Oritavancin, rifampin, and gentamicin were tested against 20 MRSE isolates recovered from prosthetic joint infection (PJI). Time-kill studies were used to evaluate the activities of the three antimicrobial agents individually vs. combinations of oritavancin with rifampin or gentamicin against MRSE biofilms formed on Teflon coupons. At 24 h, the combination of oritavancin and rifampin resulted in a significant (P≤0.001) reduction in biofilm density compared with either antimicrobial alone for 85% (17/20) of isolates. Oritavancin combined with gentamicin showed a significant (P≤0.001) reduction in biofilm density compared with either antimicrobial alone against 55% (11/20) of isolates at 24 h. Synergy (defined as a ≥2 log10 cfu/cm2 decrease at 24 h for the antimicrobial combination compared with the most active single antimicrobial) was observed against 65% (13/20) of the isolates for oritavancin in combination with rifampin and 35% (7/20) of the isolates for oritavancin in combination with gentamicin. Oritavancin in combination with rifampin or gentamicin demonstrated bactericidal activity (defined as a ≥3 log10 cfu/cm2 reduction at 24 h from the starting biofilm bacterial density) for 85% (17/20) and 80% (16/20) isolates, respectively. Our study suggests that oritavancin and rifampin combination therapy may be an option for antimicrobial management of PJIs caused by MRSE.