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Antimicrobial Agents and Chemotherapy, April 1998, p. 813-817, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activity of Amoxicillin-Clavulanate against Penicillin-Resistant Streptococcus pneumoniae in an Experimental Respiratory Infection Model in Ratsdagger

Gillian M. Smith,1 Brian Slocombe,2 Karen H. Abbott,2 and Linda W. Mizen3,*

Department of Antiinfective Research, SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania,3 and Wells Medical1 and Dorking/Ewhurst,2 Surrey, United Kingdom

Received 6 October 1997/Returned for modification 18 December 1997/Accepted 23 January 1998

High doses of amoxicillin, equivalent to those produced by 500- and 750-mg oral doses in humans (area under the plasma concentration-time curve), were effective against a penicillin-resistant strain of Streptococcus pneumoniae in an experimental respiratory tract infection in immunocompromised rats; this superior activity confirms the results of previous studies. An unexpected enhancement of amoxicillin's antibacterial activity in vivo against penicillin-resistant and -susceptible S. pneumoniae strains was observed when subtherapeutic doses of amoxicillin were coadministered with the beta -lactamase inhibitor potassium clavulanate. The reason for this enhancement was unclear since these organisms do not produce beta -lactamase. The differential binding of clavulanic acid and amoxicillin to penicillin-binding proteins may have contributed to the observed effects.

* Corresponding author. E-mail: LMizen{at}compuserve.com.

dagger Address reprint requests to James A. Poupard, Antiinfective Research, SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Rd., Mail Code UP1345, Collegeville, PA 19426-0989.

Antimicrobial Agents and Chemotherapy, April 1998, p. 813-817, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chiavolini, D., Pozzi, G., Ricci, S. (2008). Animal Models of Streptococcus pneumoniae Disease. Clin. Microbiol. Rev. 21: 666-685 [Abstract] [Full Text]  
  • Finlay, J., Miller, L., Poupard, J. A. (2003). A review of the antimicrobial activity of clavulanate. J Antimicrob Chemother 52: 18-23 [Abstract] [Full Text]  


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