Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 May;40(5):1219–1224. doi: 10.1128/aac.40.5.1219

Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

B Fantin 1, J Pierre 1, N Castéla-Papin 1, L Saint-Julien 1, H Drugeon 1, R Farinotti 1, C Carbon 1
PMCID: PMC163295  PMID: 8723470

Abstract

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

Full Text

The Full Text of this article is available as a PDF (240.8 KB).

Selected References

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

  1. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  2. Cantoni L., Wenger A., Glauser M. P., Bille J. Comparative efficacy of amoxicillin-clavulanate, cloxacillin, and vancomycin against methicillin-sensitive and methicillin-resistant Staphylococcus aureus endocarditis in rats. J Infect Dis. 1989 May;159(5):989–993. doi: 10.1093/infdis/159.5.989. [DOI] [PubMed] [Google Scholar]
  3. Caron F., Gutmann L., Bure A., Pangon B., Vallois J. M., Pechinot A., Carbon C. Ceftriaxone-sulbactam combination in rabbit endocarditis caused by a strain of Klebsiella pneumoniae producing extended-broad-spectrum TEM-3 beta-lactamase. Antimicrob Agents Chemother. 1990 Nov;34(11):2070–2074. doi: 10.1128/aac.34.11.2070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Catherall E. J., Gillon V., Hurn S., Irwin R., Mizen L. Efficacy of ticarcillin-clavulanic acid for treatment of experimental Staphylococcus aureus endocarditis in rats. Antimicrob Agents Chemother. 1992 Feb;36(2):458–462. doi: 10.1128/aac.36.2.458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chambers H. F. In vitro and in vivo antistaphylococcal activities of L-695,256, a carbapenem with high affinity for the penicillin-binding protein PBP 2a. Antimicrob Agents Chemother. 1995 Feb;39(2):462–466. doi: 10.1128/aac.39.2.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chambers H. F., Kartalija M., Sande M. Ampicillin, sulbactam, and rifampin combination treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis in rabbits. J Infect Dis. 1995 Apr;171(4):897–902. doi: 10.1093/infdis/171.4.897. [DOI] [PubMed] [Google Scholar]
  7. Chambers H. F., Sachdeva M. Binding of beta-lactam antibiotics to penicillin-binding proteins in methicillin-resistant Staphylococcus aureus. J Infect Dis. 1990 Jun;161(6):1170–1176. doi: 10.1093/infdis/161.6.1170. [DOI] [PubMed] [Google Scholar]
  8. Chambers H. F., Sachdeva M., Kennedy S. Binding affinity for penicillin-binding protein 2a correlates with in vivo activity of beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus. J Infect Dis. 1990 Sep;162(3):705–710. doi: 10.1093/infdis/162.3.705. [DOI] [PubMed] [Google Scholar]
  9. Fantin B., Carbon C. In vivo antibiotic synergism: contribution of animal models. Antimicrob Agents Chemother. 1992 May;36(5):907–912. doi: 10.1128/aac.36.5.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fantin B., Leclercq R., Duval J., Carbon C. Fusidic acid alone or in combination with vancomycin for therapy of experimental endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1993 Nov;37(11):2466–2469. doi: 10.1128/aac.37.11.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Franciolli M., Bille J., Glauser M. P., Moreillon P. Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus. J Infect Dis. 1991 Mar;163(3):514–523. doi: 10.1093/infdis/163.3.514. [DOI] [PubMed] [Google Scholar]
  12. Hartman B. J., Tomasz A. Expression of methicillin resistance in heterogeneous strains of Staphylococcus aureus. Antimicrob Agents Chemother. 1986 Jan;29(1):85–92. doi: 10.1128/aac.29.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hirano L., Bayer A. S. Beta-Lactam-beta-lactamase-inhibitor combinations are active in experimental endocarditis caused by beta-lactamase-producing oxacillin-resistant staphylococci. Antimicrob Agents Chemother. 1991 Apr;35(4):685–690. doi: 10.1128/aac.35.4.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kobayashi S., Arai S., Hayashi S., Sakaguchi T. In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1989 Mar;33(3):331–335. doi: 10.1128/aac.33.3.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Maple P. A., Hamilton-Miller J. M., Brumfitt W. World-wide antibiotic resistance in methicillin-resistant Staphylococcus aureus. Lancet. 1989 Mar 11;1(8637):537–540. doi: 10.1016/s0140-6736(89)90076-7. [DOI] [PubMed] [Google Scholar]
  16. Moellering R. C., Jr Meeting the challenges of beta-lactamases. J Antimicrob Chemother. 1993 Jan;31 (Suppl A):1–8. doi: 10.1093/jac/31.suppl_a.1. [DOI] [PubMed] [Google Scholar]
  17. Moreillon P. Amoxycillin-clavulanate versus methicillin or isoxazolyl penicillins for treatment of Staphylococcus aureus infections. J Antimicrob Chemother. 1995 Mar;35(3):435–441. doi: 10.1093/jac/35.3.435. [DOI] [PubMed] [Google Scholar]
  18. Noble W. C., Virani Z., Cree R. G. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett. 1992 Jun 1;72(2):195–198. doi: 10.1016/0378-1097(92)90528-v. [DOI] [PubMed] [Google Scholar]
  19. Pearson R. D., Steigbigel R. T., Davis H. T., Chapman S. W. Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother. 1980 Nov;18(5):699–708. doi: 10.1128/aac.18.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reynolds P. E., Brown D. F. Penicillin-binding proteins of beta-lactam-resistant strains of Staphylococcus aureus. Effect of growth conditions. FEBS Lett. 1985 Nov 11;192(1):28–32. doi: 10.1016/0014-5793(85)80036-3. [DOI] [PubMed] [Google Scholar]
  21. Sanyal D., Johnson A. P., George R. C., Cookson B. D., Williams A. J. Peritonitis due to vancomycin-resistant Staphylococcus epidermidis. Lancet. 1991 Jan 5;337(8732):54–54. doi: 10.1016/0140-6736(91)93375-j. [DOI] [PubMed] [Google Scholar]
  22. Tomasz A., Nachman S., Leaf H. Stable classes of phenotypic expression in methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother. 1991 Jan;35(1):124–129. doi: 10.1128/aac.35.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ubukata K., Yamashita N., Konno M. Occurrence of a beta-lactam-inducible penicillin-binding protein in methicillin-resistant staphylococci. Antimicrob Agents Chemother. 1985 May;27(5):851–857. doi: 10.1128/aac.27.5.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Washburn R. G., Durack D. T. Efficacy of ampicillin plus a beta-lactamase inhibitor (CP-45,899) in experimental endocarditis due to Staphylococcus aureus. J Infect Dis. 1981 Sep;144(3):237–243. doi: 10.1093/infdis/144.3.237. [DOI] [PubMed] [Google Scholar]
  25. de Lencastre H., de Jonge B. L., Matthews P. R., Tomasz A. Molecular aspects of methicillin resistance in Staphylococcus aureus. J Antimicrob Chemother. 1994 Jan;33(1):7–24. doi: 10.1093/jac/33.1.7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES