Roxithromycin as a possible agent for prophylaxis of endocarditis: a study in normal volunteers

A single dose of roxithromycin, 300 mg, was taken by six healthy male volunteers on three occasions at consecutive weekly intervals. It was well tolerated. On the first two occasions, roxithromycin was assayed in serum samples taken at intervals up to 8 h after the administration. The mean peak concentration at 1 h was 3.0 mg/l (range 0.3-7.3). The serum samples from the volunteers showed variable bactericidal activity against a strain of Streptococcus sanguis isolated from a case of bacterial endocarditis. Roxithromycin was not detected in saliva or gingival fluid. Smooth surface plaque samples taken at intervals were investigated for the emergence of streptococci resistant to roxithromycin at 2 and 8 mg/l. Initially two volunteers had small number of roxithromycin-resistant streptococci. At the end of the study all six volunteers had resistant streptococci detectable in their plaque samples and these accounted for 100% of the streptococci in two volunteers. The most resistant isolates (in several cases with MIC greater than 64 mg/l) were Str. sanguis or Str. mitior; individual volunteers tended to yield the same strain on consecutive samplings.