Synergism between cefotaxime and fosfomycin in the therapy of methicillin and gentamicin resistantStaphylococcus aureus infection in rabbits

  • P. Chavanet
  • E. Muggeo
  • A. Waldner
  • S. Dijoux
  • D. Caillot
  • H. Portier
Article

Abstract

An experimental model of infected subcutaneous fibrin clots in rabbits was used to study the synergism between cefotaxime and fosfomycin in infection with methicillin and gentamicin resistantStaphylococcus aureus (MGRSA), and to determine the efficacy of a simplified schedule of administration. The bactericidal activity of cefotaxime and fosfomycin against MGRSA was investigated giving the drugs in one full or two divided doses either alone or in combination. The pharmacokinetics of the drugs were correlated with the antibacterial efficacy obtained over 12 hours of treatment. The results confirmed that the combination of cefotaxime and fosfomycin is highly synergistic in experimental MGRSA infection. Higher bactericidal activity was obtained with a regimen of 6-hourly drug administration which resulted in persistent levels of both drugs in serum as well as at the site of infection.

Keywords

Internal Medicine Experimental Model Bactericidal Activity Gentamicin Drug Administration 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Shanson DC, Kensit JG, Duke R: Outbreak of hospital infection with a strain ofStaphylococcus aureus resistant to gentamicin and methicillin. Lancet 1976, ii: 1347–1348.Google Scholar
  2. 2.
    Soussy CJ, Dublanchet A, Cormier M, Bismuth R, Mizon F, Chardon H, Duval J, Fabiani G: Nouvelles résistances plasmidiques deStaphylococus aureus aux aminosides (gentamycine, tobramycine, amikacine). Nouvelle Presse Médicale 1976, 5: 2599–2602.Google Scholar
  3. 3.
    Maple PAC, Hamilton-Miller JMT, Brumfitt W: World-wide antibiotic resistance in methicillin-resistantStaphylococcus aureus. Lancet 1989, i: 537–540.Google Scholar
  4. 4.
    Sorrel TC, Packham DR, Shanker S, Foldes M, Munro R: Vancomycin for methicillin-resistantStaphylococcus aureus. Annals of Internal Medicine 1982, 97: 344–350.PubMedGoogle Scholar
  5. 5.
    Cafferkey MT, Hone R, Keane CT: Antimicrobial chemotherapy of septicemia due to methicillin-resistantStaphylococcus aureus. Antimicrobial Agents and Chemotherapy 1985, 28: 819–823.PubMedGoogle Scholar
  6. 6.
    Farber BF, Moellering RC: Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrobial Agents and Chemotherapy 1983, 23: 138–141.PubMedGoogle Scholar
  7. 7.
    Brumfitt W, Hamilton-Miller J: Methicillin-resistantStaphylococcus aureus. New England Journal Medicine 1989, 320: 1188–1196.Google Scholar
  8. 8.
    Sabath LD: Reappraisal of the antistaphylococcal activities of first-generaton (narrow-spectrum) and second-generation (extended-spectrum) cephalosporins. Antimicrobial Agents and Chemotherapy 1989, 33: 407–411.PubMedGoogle Scholar
  9. 9.
    Duez JM, Kohli E, Pechinot A, Tremeaux JC, Kazmierczak A: Association entre la fosfomycine et l'oxacilline ou le cefotaxime chez les staphylocoques méticilline résistants et les entérocoques.Google Scholar
  10. 10.
    Fosse T, David MF, Dulac F, Darmusey D, Tamalet C, Toga B: Etude in-vitro de l'association cefamandole-fosfomycine vis-à-vis de souches cliniques de staphylocoques methicilline-resistants. Pathologie Biologie 1984, 32: 528–531.PubMedGoogle Scholar
  11. 11.
    Alvarez S, Jones M, Berk SL: In-vitro activity of fosfomycin, alone and in combination against methicillin-resistantStaphylococcus aureus. Antimicrobial Agents and Chemotherapy 1985, 28: 689–690.PubMedGoogle Scholar
  12. 12.
    Kazmierczak A, Pechinot A, Tremeaux JC, Duez JM, Kohli E, Portier H: Bactericidal activity of cefotaxime and fosfomycin in cerebrospinal fluid during the treatment of rabbit meningitis experimentally induced by methicillin-resistantStaphylococcus aureus. Infection 1985, 13, Supplement 1: 76–80.Google Scholar
  13. 13.
    Portier H, Tremeaux JC, Chavanet P, Gouyon JB, Duez JM, Kazmierczak A: Treatment of severe staphylococcal infections with cefotaxime and fosfomycin in combination. Journal of Antimicrobial Chemotherapy 1984, 14, Supplement B: 277–284.PubMedGoogle Scholar
  14. 14.
    Bergeron MG, Nguyen BM, Trottier S, Gauvreau C: Penetration of cefamandole, cephalothin, and desacetylcephalotin into fibrin clots. Antimicrobial Agents and Chemotherapy 1977, 12: 682–687.PubMedGoogle Scholar
  15. 15.
    Sande MA, Korzeniowski OM, Allegro GM, Brennan RO, Zak O, Scheld WM: Intermittent or continuous therapy of experimental meningitis due toStreptococcus pneumoniae in rabbits: preliminary observations on the post-antibiotic effect in vivo. Reviews of Infectious Diseases 1981, 3: 98–109.PubMedGoogle Scholar
  16. 16.
    Dunnett CW: New tables for multiple comparisons with a control. Biometrics 1964, 20: 482–491.Google Scholar
  17. 17.
    Keuls M: The use of the studentized range in connection with an analysis of variance. Euphytica 1952, 1: 112–122.Google Scholar
  18. 18.
    Vogelman B, Gudmundsson S, Leggett J, Turnidge J, Ebert S, Craig A: Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. Journal of Infectious Diseases 1988, 158: 831–847.PubMedGoogle Scholar
  19. 19.
    Utsuyi Y, Ohya S, Magaribuchi T, Tajiam M, Yokota T: Antibacterial activity of cefmetazole alone and in combination with fosfomycin against methicillin-and cephem-resistantStaphylococcus aureus. Antimicrobial Agents and Chemotherapy 1986, 30: 917–922.PubMedGoogle Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 1990

Authors and Affiliations

  • P. Chavanet
    • 1
  • E. Muggeo
    • 1
  • A. Waldner
    • 1
  • S. Dijoux
    • 1
  • D. Caillot
    • 1
  • H. Portier
    • 1
  1. 1.Service des Maladies Infectieuses et TropicalesHôpital du BocageDijonFrance

Personalised recommendations