Evaluation of the synergistic effect of ceftaroline against methicillin-resistant Staphylococcus aureus

Abstract

ObjectivesWe aimed to determine the synergistic effects of ceftaroline (CPT) in combination with daptomycin (DAP), vancomycin (VAN), or linezolid (LNZ) against various methicillin-resistant Staphylococcus aureus (MRSA) strains. MethodsMRSA strains randomly selected from 2014 to 2018 were studied. Checkerboard titration and in vitro time-kill analyses were used to determine the synergistic activities of the antibiotic combinations. ResultsA total of 10 genetically distinct MRSA strains were included in this study. The checkerboard titration analysis revealed that the CPT-DAP, CPT-VAN, and CPT-LNZ combinations had a synergistic effect against 30%, 10%, and 10% of the selected MRSA strains, respectively. Using time-kill analysis, we showed that CPT-DAP exhibited a significant synergistic and sustained bactericidal effect against both DAP-susceptible (Δ colony-forming units/ml, –5.79; P = 0.0495) and DAP-resistant (Δ colony-forming units/ml, –6.40; P = 0.0463) MRSA strains at a concentration of 0.5 × the minimum inhibitory concentration of CPT plus 0.5 × the minimum inhibitory concentration of DAP. No synergistic bactericidal effects were observed for the CPT-VAN and CPT-LNZ combinations against the selected strains. ConclusionThe CPT-DAP combination showed better synergistic activity than the CPT-VAN and CPT-LNZ combinations against the enrolled MRSA strains. DAP, rather than VAN or LNZ, might be a better choice for CPT combination in the treatment of MRSA infections.