In vitro evaluation of ceftaroline alone and in combination with tobramycin against hospital-acquired meticillin-resistant Staphylococcus aureus (HA-MRSA) isolates

The aim of this study was to evaluate the in vitro activity of ceftaroline and its potential for synergy with tobramycin in comparison with vancomycin against a collection of hospital-acquired meticillin-resistant Staphylococcus aureus (HA-MRSA), including isolates with reduced susceptibility to glycopeptides. Ceftaroline, vancomycin, daptomycin and linezolid susceptibilities were determined for 200 HA-MRSA isolates. Four randomly selected strains including one vancomycin-intermediate S. aureus (VISA) and one heteroresistant VISA (hVISA)] were evaluated in time–kill experiments with ceftaroline and vancomycin alone or combined with tobramycin at 0.25 and 0.5 times the minimum inhibitory concentration (MIC). MICs for 50% and 90% of the organisms (MIC₅₀ and MIC₉₀, respectively) were both 1 mg/L for ceftaroline and were 1 mg/L and 2 mg/L, respectively, for vancomycin. The same ceftaroline MIC ranges (0.25–2 mg/L) were observed for isolates recovered from respiratory tract samples, blood or skin. In time–kill experiments, no synergy was observed at 0.25× MIC against any tested isolates with either ceftaroline or vancomycin. In contrast, the combination of ceftaroline plus tobramycin at 0.5× MIC was synergistic against the two MRSA strains and the hVISA but was indifferent against the VISA isolate. In conclusion, ceftaroline demonstrated antimicrobial activity independently of the specimen source and exhibited lower MICs than vancomycin. Finally, at sub-MIC levels, ceftaroline plus tobramycin displayed significantly greater activity than vancomycin plus tobramycin against MRSA (P < 0.01).