<i>In vitro</i> persistence of clinical methicillin-resistant <i>Staphylococcus aureus</i> isolates from bone and joint infections after exposure to daptomycin, telavancin, and vancomycin

Bacterial persistence is linked to chronic infections caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Understanding the persister profiles of daptomycin, telavancin, and vancomycin is crucial because MRSA bone and joint infections (BJIs) are associated with recurrence and treatment failure. Persister formation was assessed using quantitative <i>in vitro</i> assays against six clinical BJI MRSA isolates and a quality control ATCC strain. Assays were performed using a mid-exponential phase of bacteria challenged with steady-state drug concentrations of the three agents. Persisters were quantified as the percent survival quantifiable at 24 h compared with the respective control. Persisters were also quantified after three serial passages of daptomycin pre-exposure. The percent survival identified at 24 h was ≤21.7% with no significant differences between daptomycin, telavancin, and vancomycin in quantitative persister assays without daptomycin pre-exposure. After 3 days of <i>in vitro</i> daptomycin pre-exposure, the 24 h percent survival significantly increased compared with no pre-exposure in two isolates for the daptomycin group (100% vs 1% and 4.8% vs 0.2%, respectively). The 24 h percent persister was significantly higher in daptomycin compared with vancomycin and telavancin in four isolates. There was no significant increase in 24 h percent persister for telavancin and vancomycin after daptomycin pre-exposure. Daptomycin, telavancin, and vancomycin resulted in similar bacterial survival at 24 h at clinically achievable concentrations. Daptomycin pre-exposure did not alter persistence for telavancin and vancomycin. Considering differences in persister generation, further clinical studies are justified to help differentiate these anti-MRSA agents in the treatment of MRSA BJIs.IMPORTANCEBacterial persistence has been associated with relapsing infections, including infections caused by MRSA. Chronic infections, such as bone and joint infections, are associated with high rates of recurrence, and persistence may play a role. Although daptomycin, telavancin, and vancomycin are widely used for the treatment of bone and joint infections, their persister potential has not been assessed under the same experimental conditions. The present study sought to assess the <i>in vitro</i> persister potential of daptomycin, telavancin, and vancomycin against clinical MRSA from bone and joint infections.