Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Feb;36(2):446–452. doi: 10.1128/aac.36.2.446

Antimicrobial activity of MDL 62,873, a semisynthetic derivative of teicoplanin, in vitro and in experimental infections.

M Berti 1, G Candiani 1, M Borgonovi 1, P Landini 1, F Ripamonti 1, R Scotti 1, L Cavenaghi 1, M Denaro 1, B P Goldstein 1
PMCID: PMC188455  PMID: 1534978

Abstract

MDL 62,873 is an amide derivative of teicoplanin A2-2. Like those of natural glycopeptides, its antibacterial activity is mediated by inhibition of cell wall peptidoglycan synthesis. Against streptococci and enterococci, the in vitro activity of MDL 62,873 was similar to that of teicoplanin and greater than that of vancomycin. Against staphylococci, it has activity similar to that of vancomycin, and it was significantly more active than teicoplanin against coagulase-negative isolates. Like teicoplanin and vancomycin, MDL 62,873 had slow but significant bactericidal activity (99 to 99.9% killing in 24 h) against staphylococci at concentrations near the MIC. In murine septicemia studies with Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae, the 50% effective doses were lower than those of vancomycin. In staphylococcal endocarditis in rats, MDL 62,873 at 20 mg/kg of body weight and vancomycin at 40 mg/kg, both doses given intravenously twice daily, had similar efficacies in reducing the heart bacterial load. These results probably reflect the longer half-life of MDL 62,873, which has a pharmacokinetic profile in rats similar to that of teicoplanin.

Full text

PDF
446

Selected References

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

  1. Arioli V., Berti M., Candiani G. Activity of teicoplanin in localized experimental infections in rats. J Hosp Infect. 1986 Mar;7 (Suppl A):91–99. doi: 10.1016/0195-6701(86)90013-7. [DOI] [PubMed] [Google Scholar]
  2. Bailey E. M., Constance T. D., Albrecht L. M., Rybak M. J. Coagulase-negative staphylococci: incidence, pathogenicity, and treatment in the 1990s. DICP. 1990 Jul-Aug;24(7-8):714–720. doi: 10.1177/106002809002400715. [DOI] [PubMed] [Google Scholar]
  3. Bartoloni A., Colao M. G., Orsi A., Dei R., Giganti E., Parenti F. In-vitro activity of vancomycin, teicoplanin, daptomycin, ramoplanin, MDL 62873 and other agents against staphylococci, enterococci and Clostridium difficile. J Antimicrob Chemother. 1990 Nov;26(5):627–633. doi: 10.1093/jac/26.5.627. [DOI] [PubMed] [Google Scholar]
  4. Bernareggi A., Cavenaghi L., Assandri A. Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose. Antimicrob Agents Chemother. 1986 Nov;30(5):733–738. doi: 10.1128/aac.30.5.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borghi A., Coronelli C., Faniuolo L., Allievi G., Pallanza R., Gallo G. G. Teichomycins, new antibiotics from Actinoplanes teichomyceticus nov. sp. IV. Separation and characterization of the components of teichomycin (teicoplanin). J Antibiot (Tokyo) 1984 Jun;37(6):615–620. doi: 10.7164/antibiotics.37.615. [DOI] [PubMed] [Google Scholar]
  6. Froggatt J. W., Johnston J. L., Galetto D. W., Archer G. L. Antimicrobial resistance in nosocomial isolates of Staphylococcus haemolyticus. Antimicrob Agents Chemother. 1989 Apr;33(4):460–466. doi: 10.1128/aac.33.4.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldstein F. W., Coutrot A., Sieffer A., Acar J. F. Percentages and distributions of teicoplanin- and vancomycin-resistant strains among coagulase-negative staphylococci. Antimicrob Agents Chemother. 1990 May;34(5):899–900. doi: 10.1128/aac.34.5.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grant A. C., Lacey R. W., Brownjohn A. M., Turney J. H. Teicoplanin-resistant coagulase-negative staphylococcus. Lancet. 1986 Nov 15;2(8516):1166–1167. doi: 10.1016/s0140-6736(86)90580-5. [DOI] [PubMed] [Google Scholar]
  9. Gruer L. D., Bartlett R., Ayliffe G. A. Species identification and antibiotic sensitivity of coagulase-negative staphylococci from CAPD peritonitis. J Antimicrob Chemother. 1984 Jun;13(6):577–583. doi: 10.1093/jac/13.6.577. [DOI] [PubMed] [Google Scholar]
  10. Hunter P. R., George R. C., Griffiths J. W. Mathematical modeling of antimicrobial susceptibility data of Staphylococcus haemolyticus for 11 antimicrobial agents, including three experimental glycopeptides and an experimental lipoglycopeptide. Antimicrob Agents Chemother. 1990 Sep;34(9):1769–1772. doi: 10.1128/aac.34.9.1769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Héraïef E., Glauser M. P., Freedman L. R. Natural history of aortic valve endocarditis in rats. Infect Immun. 1982 Jul;37(1):127–131. doi: 10.1128/iai.37.1.127-131.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jones R. N., Goldstein F. W., Zhou X. Y. Activities of two new teicoplanin amide derivatives (MDL 62211 and MDL 62873) compared with activities of teicoplanin and vancomycin against 800 recent staphylococcal isolates from France and the United States. Antimicrob Agents Chemother. 1991 Mar;35(3):584–586. doi: 10.1128/aac.35.3.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kaatz G. W., Seo S. M., Dorman N. J., Lerner S. A. Emergence of teicoplanin resistance during therapy of Staphylococcus aureus endocarditis. J Infect Dis. 1990 Jul;162(1):103–108. doi: 10.1093/infdis/162.1.103. [DOI] [PubMed] [Google Scholar]
  14. Kaatz G. W., Seo S. M., Reddy V. N., Bailey E. M., Rybak M. J. Daptomycin compared with teicoplanin and vancomycin for therapy of experimental Staphylococcus aureus endocarditis. Antimicrob Agents Chemother. 1990 Nov;34(11):2081–2085. doi: 10.1128/aac.34.11.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karchmer A. W., Archer G. L., Dismukes W. E. Staphylococcus epidermidis causing prosthetic valve endocarditis: microbiologic and clinical observations as guides to therapy. Ann Intern Med. 1983 Apr;98(4):447–455. doi: 10.7326/0003-4819-98-4-447. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Malabarba A., Trani A., Strazzolini P., Cietto G., Ferrari P., Tarzia G., Pallanza R., Berti M. Synthesis and biological properties of N63-carboxamides of teicoplanin antibiotics. Structure-activity relationships. J Med Chem. 1989 Nov;32(11):2450–2460. doi: 10.1021/jm00131a007. [DOI] [PubMed] [Google Scholar]
  18. Maugein J., Pellegrin J. L., Brossard G., Fourche J., Leng B., Reiffers J. In vitro activities of vancomycin and teicoplanin against coagulase-negative staphylococci isolated from neutropenic patients. Antimicrob Agents Chemother. 1990 May;34(5):901–903. doi: 10.1128/aac.34.5.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moore E. P., Speller D. C. In-vitro teicoplanin-resistance in coagulase-negative staphylococci from patients with endocarditis and from a cardiac surgery unit. J Antimicrob Chemother. 1988 Apr;21(4):417–424. doi: 10.1093/jac/21.4.417. [DOI] [PubMed] [Google Scholar]
  20. Rybak M. J., Lerner S. A., Levine D. P., Albrecht L. M., McNeil P. L., Thompson G. A., Kenny M. T., Yuh L. Teicoplanin pharmacokinetics in intravenous drug abusers being treated for bacterial endocarditis. Antimicrob Agents Chemother. 1991 Apr;35(4):696–700. doi: 10.1128/aac.35.4.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. STRAKA R. P., STOKES J. L. Rapid destruction of bacteria in commonly used diluents and its elimination. Appl Microbiol. 1957 Jan;5(1):21–25. doi: 10.1128/am.5.1.21-25.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schwalbe R. S., Stapleton J. T., Gilligan P. H. Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med. 1987 Apr 9;316(15):927–931. doi: 10.1056/NEJM198704093161507. [DOI] [PubMed] [Google Scholar]
  23. Uttley A. H., Collins C. H., Naidoo J., George R. C. Vancomycin-resistant enterococci. Lancet. 1988 Jan 2;1(8575-6):57–58. doi: 10.1016/s0140-6736(88)91037-9. [DOI] [PubMed] [Google Scholar]
  24. Williamson R., Al-Obeid S., Shlaes J. H., Goldstein F. W., Shlaes D. M. Inducible resistance to vancomycin in Enterococcus faecium D366. J Infect Dis. 1989 Jun;159(6):1095–1104. doi: 10.1093/infdis/159.6.1095. [DOI] [PubMed] [Google Scholar]
  25. Wilson A. P., O'Hare M. D., Felmingham D., Grüneberg R. N. Teicoplanin-resistant coagulase-negative staphylococcus. Lancet. 1986 Oct 25;2(8513):973–973. doi: 10.1016/s0140-6736(86)90622-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES