title: Influence of in vitro susceptibility phenotype against thrombin-induced platelet microbicidal protein on treatment and prophylaxis outcomes of experimental Staphylococcus aureus endocarditis.
abstract: Thrombin-induced platelet microbicidal protein-1 (tPMP-1) is a small, cationic staphylocidal peptide from rabbit platelets. In the current study, the outcomes of vancomycin treatment and prophylaxis were compared in experimental infective endocarditis (IE) caused by an isogenic Staphylococcus aureus strain pair differing in tPMP-1 susceptibility (tPMPS) or resistance (tPMPR) in vitro (ISP479C and ISP479R, respectively). Vancomycin therapy (selected for its intrinsically slow bactericidal activity) reduced ISP479C (but not ISP479R) densities in vegetations compared with controls (P<.01). In contrast, prophylactic administration of vancomycin yielded no differences in efficacies for the 2 challenge strains. These data suggest that the tPMPR phenotype in vitro has a negative effect on the antimicrobial therapy (but not the prophylaxis) of experimental S. aureus IE. These disparate results may be explained in part by the requirement for microbicidal effects in the treatment of established IE, whereas prophylactic efficacy depends more on growth inhibitory and antiadhesion effects.
authors.affiliation: Division of Infectious Diseases, Charles Drew University-Martin Luther King Medical Center, UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Dhawan
authors.forename: M R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: A S
authors.initials: AS
authors.lastname: Bayer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D001798:Blood Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; C077150:platelet microbicidal protein, Oryctolagus cuniculus; D014640:Vancomycin