The objective of this study was to investigate the potential role of
ceftaroline, a new broad-spectrum
cephalosporin, as a therapeutic option for the treatment of
daptomycin-nonsusceptible (DNS) methicillin-resistant Staphylococcus aureus (MRSA)
infections. Four clinical DNS MRSA strains, R5717, R5563, R5996 (heteroresistant
vancomycin-intermediate S. aureus) and R5995 (
vancomycin-intermediate S. aureus) were evaluated in a two-compartment hollow-fiber in vitro pharmacokinetic/pharmacodynamic model at a starting inoculum of 10(7) CFU/ml for 96 h. Simulated regimens were
ceftaroline at 600 mg every 12 h (q12h) (maximum free-
drug concentration [fC(max)], 15.2 μg/ml; serum half-life [t(1/2)], 2.3 h),
daptomycin at 6 mg/kg q24h (fC(max), 7.9 μg/ml; t(1/2), 8 h), and
daptomycin at 10 mg/kg q24h (fC(max), 15.2 μg/ml; t(1/2), 8 h). Differences in CFU/ml between 24 and 96 h were evaluated by analysis of variance with Tukey's post-hoc test. Bactericidal activity was defined as a ≥3-log(10) CFU/ml decrease in the colony count from the initial inoculum. The
ceftaroline MIC values were 0.25, 0.5, 0.5, and 0.5 μg/ml, and the
daptomycin MIC values were 2, 2, 4, and 4 μg/ml for R5717, R5563, R5996, and R5995, respectively.
Ceftaroline displayed sustained bactericidal activity against 3 of the 4 strains at 96 h (R5717, -3.1 log(10) CFU/ml; R5563, -2.5 log(10) CFU/ml; R5996, -5.77 log(10) CFU/ml; R5995, -6.38 log(10) CFU/ml). Regrowth occurred during the
daptomycin at 6-mg/kg q24h regimen (4 strains) and the
daptomycin at 10-mg/kg q24h regimen (3 strains). At 96 h,
ceftaroline was significantly more active, resulting in CFU/ml counts lower than those obtained with
daptomycin at 6 mg/kg q24h (4 strains, P ≤ 0.008) and
daptomycin at 10 mg/kg q24 h (3 strains, P ≤ 0.001). Isolates with increased MIC values for
daptomycin (all 4 strains) but not for
ceftaroline were recovered.
Ceftaroline was effective against the 4 isolates tested and may provide a clinical option for the treatment of DNS MRSA
infections.