Beneficial influence of platelets on antibiotic efficacy in an in vitro model of Staphylococcus aureus-induced endocarditis.
Platelets contribute to antimicrobial host defense against infective endocarditis (IE) by releasing platelet microbicidal proteins (PMPs). We investigated the influence of thrombin-stimulated human platelets on the evolution of simulated IE in the presence and absence of vancomycin or nafcillin. Staphylococcus aureus strains differing in intrinsic susceptibility to PMPs or antibiotics were studied: ISP479C (thrombin-induced PMP-1 [tPMP-1] susceptible; nafcillin and vancomycin susceptible), ISP479R (tPMP-1 resistant; nafcillin and vancomycin susceptible), and GISA-NJ (tPMP-1 intermediate-susceptible; vancomycin intermediate-susceptible). Platelets were introduced and thrombin activated within the in vitro IE model 30 min prior to inoculation with S. aureus. At 0 to 24 h postinoculation, bacterial densities in chamber fluid and simulated endocardial vegetations (SEVs) were quantified and compared among groups. Activated platelets alone, or in combination with antibiotics, inhibited the proliferation of ISP479C in chamber fluid or SEVs over the initial 4-h period (P < 0.05 versus controls). Moreover, nafcillin-containing regimens exerted inhibitory effects beyond 4 h against ISP479C in both model phases. By comparison, activated platelets inhibited GISA-NJ proliferation in SEVs but not in chamber fluid. The combination of platelets plus nafcillin or vancomycin significantly inhibited proliferation of the GISA-NJ strain in SEVs compared to the effect of platelets or antibiotics alone (P < 0.05). In contrast, platelets did not significantly alter the antistaphylococcal efficacies of nafcillin or vancomycin against ISP479R. These data support our hypothesis that a beneficial antimicrobial effect may result from the interaction among platelets, PMPs, and anti-infective agents against antibiotic-susceptible or -resistant staphylococci that exhibit a tPMP-1-susceptible or -intermediate-susceptible phenotype.
Mercier
Renee-Claude
RC
College of Pharmacy MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA. rmercier@unm.edu
Dietz
Robert M
RM
Mazzola
Jory L
JL
Bayer
Arnold S
AS
Yeaman
Michael R
MR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000502:physiology*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006321:Heart / Q000382:microbiology; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D009254:Nafcillin / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D013210:Staphylococcus / Q000254:growth & development; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D010406:Penicillins; D009254:Nafcillin; D014640:Vancomycin