Medical device infections frequently require combination therapy. Beta-lactams combined with glycopeptides/lipopeptides are bactericidal against methicillin-resistant Staphylococcus aureus (MRSA). Novel macrowell kill-curve methods tested synergy between ceftaroline or cefazolin plus daptomycin, vancomycin, or rifampin against biofilm-producing MRSA. Ceftaroline combinations demonstrated the most pronounced bacterial reductions. Ceftaroline demonstrated greatest kill with daptomycin (4.02 ± 0.59 log10 CFU/cm(2)), compared to combination with vancomycin (3.36 ± 0.35 log10 CFU/cm(2)) or rifampin (2.68 ± 0.61 log10 CFU/cm(2)). These data suggest that beta-lactam combinations are useful against MRSA biofilms.