Experimental endocarditis in rabbits. 6. Results of long-term combined therapy of Streptococcus faecalis endocarditis with penicillin and streptomycin.

The synergistic action of penicillin and streptomycin was investigated on animals with experimental endocarditis, using the previously described model and four different strains of Streptococcus faecalis. Two strains represented a moderate and two strains a high level of resistance to streptomycin. The purpose was to determine the effect of the combined penicillin and streptomycin treatment, since previous in vitro investigations showed that strains highly resistant to streptomycin were also resistant to combination of the drugs. Antibiotic treatment of the animals was carried out for 28 days, followed by a period of four weeks observation. The treatment resulted in a demonstrable effect against infection caused by the least streptomycin-resistant strain, but was completely ineffective in rabbits infected with the strain homogeneously resistant to 8000 micrograms/ml streptomycin. The synergistic effect of penicillin and streptomycin towards strains within a range of streptomycin resistance of 2000-8000 micrograms/ml could be predicted by the IC50 test, but not by MIC or the in vitro killing curve test for synergism. Besides the therapeutic results, this report also considers the following features: pathoanatomic and physiologic processes related to the number of viable bacteria in the endocardial vegetations; the influence of the proteolytic capacity of infecting strains; the development of congestive heart failure.