Vancomycin prophylaxis of experimental Streptococcus sanguis. Inhibition of bacterial adherence rather than bacterial killing.
Using a strain of Streptococcus sanguis tolerant to vancomycin to infect aortic vegetations in rats, we found that prophylactic intravenous vancomycin given 30 min before bacterial challenge decreased the incidence of endocarditis from 88 to 8% (P less than 10(-5)). Because peak vancomycin serum levels were below the minimal bactericidal concentration, mechanisms of protection other than bacterial killing were investigated. S. sanguis were incubated with inhibitory concentration of vancomycin (50 microgram/ml) for 10 h and washed. 85% of rats (73/86) inoculated with control bacteria developed endocarditis, whereas only 42% (33/78) of those inoculated with vancomycin-exposed bacteria did so (P less than 10(-5)). When rats were killed 30 min after bacterial challenge, S. sanguis were detected by culture of the vegetations in 44% of rats injected with control bacteria, but in only 13% of those challenged with vancomycin-exposed bacteria (P less than 0.03). Enhanced clearance of vancomycin-exposed streptococci was not responsible for this protection because blood cultures showed no difference in the level and duration of bacteremia after injection of control or vancomycin-exposed S. sanguis. Moreover, this protection was not abolished in neutropenic rats injected with vancomycin-exposed bacteria, despite more prolonged bacteremia. These results suggest that vancomycin exerted its protection by lowering adherence of tolerant S. sanguis to vegetations rather than through bactericidal activity or enhanced clearance of bacteria by phagocytic cells. In the choice of antibiotics for prophylaxis of endocarditis, reduction of bacterial adhesion may be a criterion as important as bacterial killing.
D000818:Animals; D001770:Blood Bactericidal Activity; D002448:Cell Adhesion / Q000187:drug effects; D004697:Endocarditis, Bacterial / Q000517:prevention & control*; D005260:Female; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013298:Streptococcus sanguis / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
D014640:Vancomycin