Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1990 Sep;34(9):1792–1794. doi: 10.1128/aac.34.9.1792

Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis.

M L Grayson 1, C Thauvin-Eliopoulos 1, G M Eliopoulos 1, J D Yao 1, D V DeAngelis 1, L Walton 1, J L Woolley 1, R C Moellering Jr 1
PMCID: PMC171927  PMID: 2126691

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.

Full text

PDF
1792

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Courvalin P., Carlier C., Collatz E. Plasmid-mediated resistance to aminocyclitol antibiotics in group D streptococci. J Bacteriol. 1980 Aug;143(2):541–551. doi: 10.1128/jb.143.2.541-551.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crider S. R., Colby S. D. Susceptibility of enterococci to trimethoprim and trimethoprim-sulfamethoxazole. Antimicrob Agents Chemother. 1985 Jan;27(1):71–75. doi: 10.1128/aac.27.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Goodhart G. L. In vivo v in vitro susceptibility of enterococcus to trimethoprim-sulfamethoxazole. A pitfall. JAMA. 1984 Nov 16;252(19):2748–2749. [PubMed] [Google Scholar]
  4. Grose W. E., Bodey G. P., Loo T. L. Clinical pharmacology of intravenously administered trimethoprim-sulfamethoxazole. Antimicrob Agents Chemother. 1979 Mar;15(3):447–451. doi: 10.1128/aac.15.3.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hoffmann S. A., Moellering R. C., Jr The enterococcus: "putting the bug in our ears". Ann Intern Med. 1987 May;106(5):757–761. doi: 10.7326/0003-4819-106-5-757. [DOI] [PubMed] [Google Scholar]
  6. Horodniceanu T., Bougueleret L., El-Solh N., Bieth G., Delbos F. High-level, plasmid-borne resistance to gentamicin in Streptococcus faecalis subsp. zymogenes. Antimicrob Agents Chemother. 1979 Nov;16(5):686–689. doi: 10.1128/aac.16.5.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kuhne J., Kohlmann F. W., Seydel J. K., Wempe E. Pharmakokinetik der Kombination Sulfamoxol/Trimethoprim (CN 3123) bei Tier und Mensch. Arzneimittelforschung. 1976;26(42):651–657. [PubMed] [Google Scholar]
  8. Lagler F., Kretzschmar R., Leuschner F., Foitzik E., Kiel H., Kuhne J., Neumann W. Toxikologische Untersuchungen der Kombination Sulfamoxol/Trimethoprim (CN 3123), eines neuen Breitbandchemotherapeutikums. Arzneimittelforschung. 1976;26(42):634–643. [PubMed] [Google Scholar]
  9. Leclercq R., Derlot E., Duval J., Courvalin P. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med. 1988 Jul 21;319(3):157–161. doi: 10.1056/NEJM198807213190307. [DOI] [PubMed] [Google Scholar]
  10. Maki D. G., Agger W. A. Enterococcal bacteremia: clinical features, the risk of endocarditis, and management. Medicine (Baltimore) 1988 Jul;67(4):248–269. [PubMed] [Google Scholar]
  11. Mederski-Samoraj B. D., Murray B. E. High-level resistance to gentamicin in clinical isolates of enterococci. J Infect Dis. 1983 Apr;147(4):751–757. doi: 10.1093/infdis/147.4.751. [DOI] [PubMed] [Google Scholar]
  12. Murray B. E., Mederski-Samaroj B. Transferable beta-lactamase. A new mechanism for in vitro penicillin resistance in Streptococcus faecalis. J Clin Invest. 1983 Sep;72(3):1168–1171. doi: 10.1172/JCI111042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Murray B. E., Tsao J., Panida J. Enterococci from Bangkok, Thailand, with high-level resistance to currently available aminoglycosides. Antimicrob Agents Chemother. 1983 Jun;23(6):799–802. doi: 10.1128/aac.23.6.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Najjar A., Murray B. E. Failure to demonstrate a consistent in vitro bactericidal effect of trimethoprim-sulfamethoxazole against enterococci. Antimicrob Agents Chemother. 1987 May;31(5):808–810. doi: 10.1128/aac.31.5.808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Santoro J., Levison M. E. Rat model of experimental endocarditis. Infect Immun. 1978 Mar;19(3):915–918. doi: 10.1128/iai.19.3.915-918.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schwartz D. E., Vetter W., Englert G. Trimethoprim metabolites in rat, dog and man: qualitative and quantitative studies. Arzneimittelforschung. 1970 Dec;20(12):1867–1871. [PubMed] [Google Scholar]
  17. Schwartz D. E., Ziegler W. H. Assay and pharmacokinetics of trimethoprim in man and animals. Postgrad Med J. 1969 Nov;45(Suppl):32–37. [PubMed] [Google Scholar]
  18. Thauvin C., Eliopoulos G. M., Willey S., Wennersten C., Moellering R. C., Jr Continuous-infusion ampicillin therapy of enterococcal endocarditis in rats. Antimicrob Agents Chemother. 1987 Feb;31(2):139–143. doi: 10.1128/aac.31.2.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tofte R. W., Solliday J. A., Crossley K. B. Susceptibilities of enterococci to twelve antibiotics. Antimicrob Agents Chemother. 1984 Apr;25(4):532–533. doi: 10.1128/aac.25.4.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zervos M. J., Schaberg D. R. Reversal of the in vitro susceptibility of enterococci to trimethoprim-sulfamethoxazole by folinic acid. Antimicrob Agents Chemother. 1985 Sep;28(3):446–448. doi: 10.1128/aac.28.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES