The treatment of prosthetic joint
infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to be a challenge for the clinician. The aim of this study was to evaluate the efficacies of
daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg of
body weight/day, respectively, in humans) and in combination with
rifampin and to compare the activities to those of conventional anti-MRSA
therapies. We used MRSA strain HUSA 304, with the following MICs and minimal bactericidal concentrations (MBCs), respectively:
daptomycin, 1 μg/ml and 4 μg/ml;
vancomycin, 2 μg/ml and 4 μg/ml;
linezolid, 2 μg/ml and >32 μg/ml; and
rifampin, 0.03 μg/ml and 0.5 μg/ml. In time-kill curves, only
daptomycin and its combinations with
rifampin achieved a bactericidal effect in log and stationary phases. For in vivo studies, we used a rat
foreign-body infection model.
Therapy was administered for 7 days with
daptomycin at 100 mg/kg/day and 45/mg/kg/day,
vancomycin at 50 mg/kg/12 h,
rifampin at 25 mg/kg/12 h, and
linezolid at 35 mg/kg/12 h, and each
antibiotic was also combined with
rifampin. Among monotherapies,
daptomycin at 100 mg/kg/day and
rifampin performed better than
vancomycin and
linezolid. In combination with
rifampin, both dosages of
daptomycin were significantly better than all other combinations, but
daptomycin at 100 mg/kg/day plus
rifampin achieved better cure rates at day 11 (P < 0.05) than
daptomycin at 45 mg/kg/day plus
rifampin. Resistant strains were found in monotherapies with
rifampin and
daptomycin at 45 mg/kg/day. In conclusion,
daptomycin at high doses was the most effective monotherapy and also improved the efficacy of the combination with
rifampin against
foreign-body infections by MRSA. Clinical studies should confirm whether this combination may be considered the first-line treatment for
foreign-body infections by MRSA in humans.