Comparison of a rabbit model of bacterial endocarditis and an in vitro infection model with simulated endocardial vegetations

Animal models are commonly used to determine the efficacy of various antimi crobial agents for treatment of bacterial endocarditis, Previously we have utilized an in vitro infection model, which incorporates simulated endocard ial vegetations (SEVs) to evaluate the pharmacodynamics of various antibiot ics. In the present study, we compared four experimental rabbit endocarditi s protocols to an in vitro infection model in an effort to deter mine if th ese models are comparable. We have evaluated the activity of clinafloxacin, trovafloxacin, sparfloxacin, and ciprofloxacin in rabbit models against St aphylococcus aureus and Enterococcus spp, In vitro models were performed si mulating the antibiotic pharmacokinetics obtained in the in vivo studies, M odels were dosed the same as rabbit models, and SEVs were evaluated at the same time the rabbit vegetations were examined. Clinafloxacin and trovaflox acin were evaluated against methicillin-susceptible (MSSA1199) and -resista nt (MRSA494) strains of S. aureus. Ciprofloxacin was studied against MSSA11 99 and MSSA487. Sparfloxacin and clinafloxacin were evaluated against Enter ococcus faecium SF2149 and Enterococcus faecalis WH245, respectively, We fo und that reductions in SEV bacterial density obtained in the in vitro model were similar to those obtained in rabbit vegetations, indicating that the SEV model may be a valuable tool for assessing antibiotic potential in the treatment of bacterial endocarditis.