Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis.
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.
Grayson
M L
ML
Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts 02215.
Thauvin-Eliopoulos
C
C
Eliopoulos
G M
GM
Yao
J D
JD
DeAngelis
D V
DV
Walton
L
L
Woolley
J L
JL
Moellering
R C
RC
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*
D000667:Ampicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination