Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis

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Abstract
To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 .+-. 1.1 versus 8.6 .+-. 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 .+-. 1.5 log10 CFU/g; P .ltoreq. 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection.