Influence of the pre-treatment duration of infection on the efficacies of various antibiotic regimens in experimental streptococcal endocarditis

Abstract

The influence of the pre-treatment duration of infection on the efficacies of three different antibiotic regimens was investigated in a rabbit model of subacute endocarditis caused by a novel, nutritionally-variant species, Streptococcus adjacens strain GaDT. Treatment was initiated either 6 or 10 days after bacterial inoculation (days 7 and 11 respectively) and comprised procaine penicillin (150,000 IU/kg bd), alone or combined with tobramycin (12 mg/kg od), teicoplanin (10 mg/kg bd), all administered by the intramuscular route for 4 days. The MICs and MBCs of penicillin, tobramycin and teicoplanin were 0.015 and 1 mg/L, 8 and 16 mg/L and 0.25 and 256 mg/L respectively. In the control rabbits, the mean (+/- S.D.) weights of the vegetations were 25 +/- 16 mg on day 7 and 45 +/- 34 mg on day 11 (P = 0.06). The mean (+/- S.D.) reductions in the number of cfu in the vegetations of the treated groups of animals after completion of therapy which had been started on days 7 and 11, compared with the mean numbers of cfu in the vegetations of the untreated controls on days 7 and 11 (delta log10 cfu/g), were 4.0 +/- 1.3 and 2.1 +/- 1.5 respectively for penicillin (P < 0.05), 3.2 +/- 1.8 and 2.4 +/- 1.8 respectively for teicoplanin and 5.4 +/- 1.2 and 5.2 +/- 1.2 respectively for the combination of penicillin and tobramycin. The increase in the size of the vegetations and changes in the metabolism of the bacteria within the vegetations between days 7 and 11, as demonstrated by electron microscopy, might explain why penicillin was more effective earlier in the course of the disease and why the influence of the duration of infection before treatment was initiated, varied according to the antibiotic regimen. These results suggest that the use of bactericidal regimens, such as the combination of penicillin and tobramycin, which are equally effective in reducing the bacterial counts in vegetations which have been infected for both long and short periods could minimize the risk of relapse in patients with endocarditis in whom there have been long delays before initiating treatment and/or who have large vegetations.