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AbstractThere is an increasing need for new synergistic antimicrobial combinations against multidrug-resistant bacteria. Our objective was to evaluate the activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against methicillin-resistant Staphylococcus aureus(MRSA) isolates recovered at two centers in Turkey. Activities of ceftaroline and ceftobiprole were tested against 100 MRSA isolates using gradient diffusion method. Activities of ceftaroline and ceftobiprole in combination with trimethoprim/sulfamethoxazole against 20 selected isolates (including all isolates that were non-susceptible to ceftaroline or ceftobiprole, and randomly selected isolates) were investigated using MIC:MIC ratio method. Antimicrobial interactions were interpreted using the fractional inhibitory concentration (FIC) index. The MIC50/MIC90values for ceftaroline and ceftobiprole were 0.75/1 and 1/1.5 mg/L, respectively. Ceftaroline and ceftobiprole susceptibility rates among 100 MRSA isolates were 94% and 96%, respectively. Ceftaroline, ceftobiprole and trimethoprim/sulfamethoxazole MICs of isolates were not increased when ceftaroline or ceftobiprole was combined with trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination demonstrated additivity against 35%, whereas ceftaroline- trimethoprim/sulfamethoxazole combination demonstrated additivity against 10% of 20 MRSA isolates. The remaining interactions for MRSA isolates were indifference. Three (75%) of four ceftobiprole-resistant isolates became susceptible to ceftobiprole after adding trimethoprim/sulfamethoxazole. None of the ceftaroline non-susceptible isolates became susceptible to ceftaroline after adding trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination may be a better treatment option than ceftaroline- trimethoprim/sulfamethoxazole combination for MRSA infections. Clinical studies are needed to confirm the results of our in vitrostudy.