The effect of roxithromycin on the virulence of gram-positive cocci

Antibiotics whose recognized mode of action comprises inhibition of bacterial protein biosynthesis are also recognized to modulate the expression of bacterial virulence factors when incorporated into culture media at sub-MIC levels. In this respect, one of the new macrolides, roxithromycin, has been examined for its effect on toxin/enzyme production by strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Biosynthesis of staphylococcal coagulase and DNase could be potentiated, whereas that of staphylococcal alpha-hemolysin, streptolysins O and S, and pneumolysin were unaltered. Expression of one structural virulence factor, pneumococcal polysaccharide, was repressed in the drug's presence, resulting in potentiation of phagocytic ingestion of the drug-exposed bacteria. The drug failed to have any effect on ingestion of Staph. aureus or Strep. pyogenes. These studies provide evidence that roxithromycin may exhibit "added value" as an antibiotic in its ability to potentiate the susceptibility of Strep. pneumoniae to host defenses such as phagocytosis.