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Antimicrobial Agents and Chemotherapy, September 2002, p. 2878-2884, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2878-2884.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of Neutrophils on Cefazolin Activity and Penicillin-Binding Proteins in Staphylococcus aureus Abscesses

David M. Bamberger,* Betty L. Herndon, Jeffrey Fitch, Aaron Florkowski, and Vera Parkhurst

Section of Infectious Diseases, Department of Medicine, University of Missouri—Kansas City, Kansas City, Missouri

Received 21 June 2001/ Returned for modification 26 September 2001/ Accepted 1 May 2002

Bacteria survive within abscesses despite antimicrobial therapy, usually necessitating drainage. Our previous work showed that bacterial killing is diminished within the neutrophils of animals with abscesses. To further assess the role of neutrophils in Staphylococcus aureus survival and the poor activities of ß-lactams in abscesses, tissue cage abscess-bearing rats were given polymorphonuclear leukocyte (PMN)-depleting antibody prior to and several times following inoculation of the tissue cages with S. aureus. Cefazolin (300 mg/kg of body weight/day) was administered to all animals in appropriately divided doses. After 7 days of antimicrobial therapy, the 17 animals that received anti-PMN serum had significantly fewer abscess neutrophils than the 18 controls and fewer abscess bacteria (5.55 versus 3.79 log10 CFU/ml [P = 0.04]) than the 18 controls. The data were consistent with the premise that cefazolin is more effective in abscesses depleted of neutrophils. To investigate further, S. aureus was incubated with rat peritoneal neutrophils; and bacterial cell membrane proteins were isolated, labeled with biotinylated ampicillin, separated by electrophoresis, blotted onto nitrocellulose, and stained for biotin reactivity. PBP 2 expression was consistently and significantly decreased after a brief, nonkilling PMN exposure. These experiments showed that PMN depletion enhanced the activity of cefazolin in the abscess milieu. Furthermore, altered bacterial cell wall cefazolin targets may be the mechanism by which the PMN diminishes antimicrobial activity, suggesting the importance of the staphylococcus-PMN interaction in the outcome of established infections.

* Corresponding author. Mailing address: Red 4 Unit, UMKC School of Medicine, 2411 Holmes St., Kansas City, MO 64108. Phone: (816) 235-1942. Fax: (816) 235-5538. E-mail: bambergerd{at}umkc.edu.

Antimicrobial Agents and Chemotherapy, September 2002, p. 2878-2884, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2878-2884.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wright, J. S. III, Jin, R., Novick, R. P. (2005). Transient interference with staphylococcal quorum sensing blocks abscess formation. Proc. Natl. Acad. Sci. USA 102: 1691-1696 [Abstract] [Full Text]  


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