TREATMENT OF EXPERIMENTAL ENDOCARDITIS DUE TO PENICILLIN-RESISTANT STREPTOCOCCUS-PNEUMONIAE

Using two strains of pneumococci for which MICs of penicillin were 1 a nd 4 mu g/ml, those of cefotaxime were 0.01 and 0.5 mu g/ml, and those of teicoplanin were 0.01 and 0.1 mu g/ml, we studied the efficacy of different dosages of penicillin, cefotaxime, and teicoplanin in the tr eatment of experimental pneumococcal endocarditis in rabbits. Animals treated with dosages of penicillin G procaine needed to achieve levels in serum near the MIC for pnenmococci showed a significant reduction in log(10) CFU per gram of vegetation, as compared with the control (P < 0.001), although only 20% of the animals showed sterile vegetations . When levels of penicillin in serum were in the range of three- to fo urfold the MIC, a greater reduction in log(10) CFU per gram of vegetat ion was seen, and 88% of the animals showed sterile vegetations. Only the regimen of penicillin that provided concentrations in serum above the MIC throughout the interval between two doses provided constant st erilization of the cardiac vegetations. Dosages of cefotaxime and teic oplanin selected to achieve concentrations in serum equivalent to that obtained in humans during treatment resulted in levels of antimicrobi al agents in serum hundreds or thousands of times higher than the MICs for the infecting strains. In terms of antimicrobial efficacy, cefota xime and teicoplanin were equivalent to regimens with high dosages of penicillin.