Cephalosporin-Aminoglycoside Synergism in Experimental Enterococcal Endocarditis

Despite in vitro demonstrations of synergism against enterococci, combinations of cephalosporin and aminoglycoside antibodies have been ineffective in the therapy of enterococcal endocarditis. Penicillin-gentamicin, cephalothin-gentamicin, and cefazolin-gentamicin were used to treat enterococcal endocarditis in rabbits. A direct relation was observed between the rate of cure and the degree by which the peak serum concentration of penicillin and the cephalosporins exceeded the minimal inhibitory concentration of the enterococcus. Thus, cephalosporin doses which produce serum concentrations which exceed the minimal inhibitory concentration of the enterococcus by several orders of magnitude may, in combination with aminoglycosides, be effective in treating human enterococcal endocarditis.