ANTIBIOTIC-TREATMENT OF EXPERIMENTAL ENDOCARDITIS DUE TO METHICILLIN-RESISTANT STAPHYLOCOCCUS-EPIDERMIDIS

The natural history and treatment of experimental endocarditis due to heterogeneous and homogeneous methicillin-resistant Staphylococcus epi dermidis was investigated. Amoxicillin/lavulanate or vancomycin were a dministered for 3 days via a computerized pump to mimic human drug kin etics in animals. After challenge with the minimum inoculum producing 90% of infections (ID90), bacteria in the vegetations grew logarithmic ally for 16 h. Then, bacterial densities stabilized (at similar to 10( 8) cfu/g) and growth rates sharply declined. Both regimens cured great er than or equal to 60% of endocarditis (due to heterogeneous or homog eneous bacteria) when started 12-16 h after infection, although the ba cterial densities in the vegetations had increased by 20 times in betw een. In contrast, treatment started after 24 h failed in most animals, while bacterial densities had not increased any more. Thus, while bot h regimens were equivalent, the therapeutic outcome was best predicted by growth rates in the vegetations, not by bacterial densities. These observations highlight the importance of phenotypic tolerance develop ing in vivo.