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

Abstract

Objectives: We 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. Methods: MRSA 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. Results: A 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. Conclusion: The 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.

Keywords

• Methicillin-resistant Staphylococcus aureus
• Ceftaroline
• Synergy
• Daptomycin
• Linezolid
• Vancomycin