title: Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis.
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 less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection.
authors: Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts 02215.
authors: M L
authors: ML
authors: Grayson
authors: C
authors: C
authors: Thauvin-Eliopoulos
authors: G M
authors: GM
authors: Eliopoulos
authors: J D
authors: JD
authors: Yao
authors: D V
authors: DV
authors: DeAngelis
authors: L
authors: L
authors: Walton
authors: J L
authors: JL
authors: Woolley
authors: R C
authors: RC
authors: Moellering
mesh_terms: D000667:Ampicillin / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D013293:Enterococcus faecalis; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013290:Streptococcal Infections / Q000188:drug therapy / Q000401:mortality; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000667:Ampicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination