Influence of in vitro susceptibility phenotype against thrombin-induced platelet microbicidal protein on treatment and prophylaxis outcomes of experimental Staphylococcus aureus endocarditis

Thrombin-induced platelet microbicidal protein-1 (tPMP-1) is a small, catio nic staphylocidal peptide from rabbit platelets. In the current study, the outcomes of vancomycin treatment and prophylaxis were compared in experimen tal infective endocarditis (IE) caused by an isogenic Staphylococcus aureus strain pair differing in tPMP-1 susceptibility (tPMP(S)) or resistance (tP MP(R)) in vitro (ISP479C and ISP479R, respectively). Vancomycin therapy (se lected for its intrinsically slow bactericidal activity) reduced ISP479C (b ut not ISP479R) densities in vegetations compared with controls (P <.01), I n contrast, prophylactic administration of vancomycin yielded no difference s in efficacies for the 2 challenge strains. These data suggest that the tP MPR phenotype in vitro has a negative effect on the antimicrobial therapy ( but not the prophylaxis) of experimental S. aureus IE. These disparate resu lts may be explained in part by the requirement for microbicidal effects in the treatment of established IE, whereas prophylactic efficacy depends mor e on growth inhibitory and antiadhesion effects.