Staphylococcal endocarditis in rabbits treated with a low dose of cloxacillin.

Rabbits with established staphylococcal endocarditis, injected twice at an interval of 2 h with either 0.5 mg of cloxacillin per kg or saline, were sacrificed 2.5 h after the second injection. Vegetations were excised, weighed, and cultured, and ultrathin sections were prepared and examined by light microscopy, transmission electron microscopy, and scanning electron microscopy. Several affected valves were examined histologically. Concentrations of cloxacillin in serum were determined 1 and 3 h after dosage. Staphylococci grown on membranes placed on agar containing 0.09 micrograms of cloxacillin per ml and in broth at the same cloxacillin concentration (one-third of the MIC) were examined by transmission electron microscopy. The mean numbers of CFU per gram of vegetations from control and treated rabbits were 2.28 X 10(10) and 1.31 X 10(10), respectively. Vegetations of treated rabbits contained staphylococci of normal size and form as well as organisms two to six times larger than normal with multiple cross walls. Larger bacterial cells were usually located in areas close to blood; cells of normal size were usually embedded in fibrin. The structures of these staphylococci and those grown on membranes in the presence of 0.09 micrograms of cloxacillin per ml were comparable but were different from those grown in broth containing this concentration of cloxacillin. Concentrations of cloxacillin in serum were 0.166 micrograms/ml at 1 h and 0.286 micrograms/ml at 3 h after dosage. The similarities in ultrastructure between staphylococci in vegetations of treated rabbits and staphylococci grown on membranes suggest that the vegetations contained approximately 0.09 micrograms of cloxacillin per g. Thus, antibiotic penetration from blood into vegetations and diffusion into fibrin were limited.