The activity of
RP 59500 against methicillin-resistant Staphylococcus aureus was studied in vitro and in a rabbit model of aortic valve
endocarditis. Three strains, 67-O, 529, and Du, ranging from relatively resistant to susceptible to
RP 59500 in vitro (mean
agar dilution MICs of 0.65, 0.21, and 0.12 mg/L respectively) were used to establish
endocarditis, which was treated either with
RP 59500, 20 mg/kg im four times a day for four days or with
vancomycin, 25 mg/kg iv twice a day for four days.
RP 59500 was ineffective for the most resistant strain, 67-O.
RP 59500 was effective for the intermediately susceptible strain 529, but
vancomycin was more effective.
RP 59500 was slightly more effective than
vancomycin against the most susceptible strain, Du, but the difference was not statistically significant. These results suggest that strains inhibited by
RP 59500 at a concentration of greater than or equal to 0.5 mg/L should probably be considered resistant in this model of
infection.
RP 59500 was effective in vivo against the two susceptible strains, but overall,
vancomycin was the more active
drug.