Activity of linezolid and high-dose daptomycin, alone or in combination, in an in vitro model of Staphylococcus aureus biofilm

The aim of the study was to assess the in vitro activity of linezolid and daptomycin, alone and in combination, against three Staphylococcus aureus isolates using a pharmacokinetic/pharmacodynamic (PK/PD) model of biofilm for 3 days. One non-clinical methicillin-resistant S. aureus isolate (N315) and two clinical methicillin-resistant S. aureus isolates were evaluated. Simulated regimens included high-dose daptomycin (10 mg/kg once daily) and linezolid (600 mg twice daily), alone and in combination. Against all three strains, neither linezolid nor daptomycin alone was bactericidal against biofilm-embedded bacteria (BB). Against planktonic bacteria (PB) only daptomycin was bactericidal. In contrast, the combination of linezolid and daptomycin demonstrated greater activity than either of the two agents alone, being bactericidal against both PB and BB, almost reaching the limit of detection at 72 h. In this in vitro PK/PD model of mature biofilms, a combination of linezolid plus daptomycin was more effective than each agent alone, representing another potential option to treat S. aureus biofilm-associated infections.