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. 1993 Feb;37(2):203–206. doi: 10.1128/aac.37.2.203

beta-Lactamase-mediated inactivation and efficacy of cefazolin and cefmetazole in Staphylococcus aureus abscesses.

M T Fields 1, B L Herndon 1, D M Bamberger 1
PMCID: PMC187639  PMID: 8452349

Abstract

12694668 Clinical reports and animal models have demonstrated that cefazolin may have decreased efficacy against some strains of Staphylococcus aureus because of type A beta-lactamase-mediated hydrolysis. We sought to measure biologically active cefazolin concentrations within abscesses with high concentrations of S. aureus and compare the concentrations with those of cefmetazole, a beta-lactamase-stable cephamycin. A type A beta-lactamase-producing strain of S. aureus with a demonstrated inoculum effect against cefazolin (MIC at an inoculum of 5 x 10(5) CFU/ml, 1.0 micrograms/ml; MIC at an inoculum of 5 x 10(7) CFU/ml, 32.0 micrograms/ml) but not cefmetazole (MICs at inocula of 5 x 10(5) and 5 x 10(7) CFU/ml, 2.0 micrograms/ml) was used. Cefazolin or cefmetazole (100 mg/kg of body weight every 8 h for 8 days) was administered to rabbits with infected tissue cages. No differences in the concentrations of the two drugs in the uninfected tissue cages were observed. Higher concentrations of cefmetazole than cefazolin were found in infected tissue cages at day 3 (5.9 +/- 0.7 versus 2.2 +/- 0.3 micrograms/ml; P < 0.01), day 5 (9.1 +/- 2.6 versus 3.6 +/- 0.7 micrograms/ml; P = 0.02), and day 8 (9.4 +/- 1.4 versus 4.8 +/- 0.9 micrograms/ml; P = 0.01) after infection. Cefazolin and cefmetazole were equally effective in reducing the bacterial concentration in the abscess. In vitro experiments demonstrated greater cefazolin than cefmetazole degradation by S. aureus, but the differences were greater in serum than in abscess fluid supernatants. We conclude that abscess cefazolin concentrations are diminished by type A beta-lactamase-producing S. aureus, but this did not affect drug efficacy in this model.

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Selected References

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  1. Bamberger D. M., Fields M. T., Herndon B. L. Efficacies of various antimicrobial agents in treatment of Staphylococcus aureus abscesses and correlation with in vitro tests of antimicrobial activity and neutrophil killing. Antimicrob Agents Chemother. 1991 Nov;35(11):2335–2339. doi: 10.1128/aac.35.11.2335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bryant R. E., Alford R. H. Unsuccessful treatment of staphylococcal endocarditis with cefazolin. JAMA. 1977 Feb 7;237(6):569–570. [PubMed] [Google Scholar]
  3. Carrizosa J., Kobasa W. D., Snepar R., Kaye K. M., Kaye D. Cefazolin versus cephalothin in beta-lactamase-producing Staphylococcus aureus endocarditis in a rabbit experimental model. J Antimicrob Chemother. 1982 May;9(5):387–393. doi: 10.1093/jac/9.5.387. [DOI] [PubMed] [Google Scholar]
  4. Chapman S. W., Steigbigel R. T. Staphylococcal beta-lactamase and efficacy of beta-lactam antibiotics: in vitro and in vivo evaluation. J Infect Dis. 1983 Jun;147(6):1078–1089. doi: 10.1093/infdis/147.6.1078. [DOI] [PubMed] [Google Scholar]
  5. Edwards W. H., Jr, Kaiser A. B., Kernodle D. S., Appleby T. C., Edwards W. H., Sr, Martin R. S., 3rd, Mulherin J. L., Jr, Wood C. A., Jr Cefuroxime versus cefazolin as prophylaxis in vascular surgery. J Vasc Surg. 1992 Jan;15(1):35–42. doi: 10.1067/mva.1992.33841. [DOI] [PubMed] [Google Scholar]
  6. Gerding D. N., Hall W. H., Schierl E. A., Manion R. E. Cephalosporin and aminoglycoside concentrations in peritoneal capsular fluid in rabbits. Antimicrob Agents Chemother. 1976 Dec;10(6):902–911. doi: 10.1128/aac.10.6.902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gerding D. N., Van Etta L. L., Peterson L. R. Role of serum protein binding and multiple antibiotic doses in the extravascular distribution of ceftizoxime and cefotaxime. Antimicrob Agents Chemother. 1982 Nov;22(5):844–847. doi: 10.1128/aac.22.5.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldman P. L., Petersdorf R. G. Importance of beta-lactamase inactivation in treatment of experimental endocarditis caused by Staphylococcus aureus. J Infect Dis. 1980 Mar;141(3):331–337. doi: 10.1093/infdis/141.3.331. [DOI] [PubMed] [Google Scholar]
  9. Jones R. N. Cefmetazole (CS-1170), a "new" cephamycin with a decade of clinical experience. Diagn Microbiol Infect Dis. 1989 Sep-Oct;12(5):367–379. doi: 10.1016/0732-8893(89)90106-5. [DOI] [PubMed] [Google Scholar]
  10. Kaiser A. B., Petracek M. R., Lea J. W., 4th, Kernodle D. S., Roach A. C., Alford W. C., Jr, Burrus G. R., Glassford D. M., Jr, Thomas C. S., Jr, Stoney W. S. Efficacy of cefazolin, cefamandole, and gentamicin as prophylactic agents in cardiac surgery. Results of a prospective, randomized, double-blind trial in 1030 patients. Ann Surg. 1987 Dec;206(6):791–797. doi: 10.1097/00000658-198712000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kernodle D. S., Classen D. C., Burke J. P., Kaiser A. B. Failure of cephalosporins to prevent Staphylococcus aureus surgical wound infections. JAMA. 1990 Feb 16;263(7):961–966. [PubMed] [Google Scholar]
  12. Kernodle D. S., McGraw P. A., Stratton C. W., Kaiser A. B. Use of extracts versus whole-cell bacterial suspensions in the identification of Staphylococcus aureus beta-lactamase variants. Antimicrob Agents Chemother. 1990 Mar;34(3):420–425. doi: 10.1128/aac.34.3.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Komiya M., Kikuchi Y., Tachibana A., Yano K. Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals. Antimicrob Agents Chemother. 1981 Aug;20(2):176–183. doi: 10.1128/aac.20.2.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Matsui H., Okuda T. Penetration of cefpiramide and cefazolin into peritoneal capsular fluid in rabbits. Antimicrob Agents Chemother. 1988 Jan;32(1):33–36. doi: 10.1128/aac.32.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Murakawa T., Sakamoto H., Fukada S., Nakamoto S., Hirose T., Itoh N., Nishida M. Pharmacokinetics of ceftizoxime in animals after parenteral dosing. Antimicrob Agents Chemother. 1980 Feb;17(2):157–164. doi: 10.1128/aac.17.2.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. O'Keefe J. P., Tally F. P., Barza M., Gorbach S. L. Inactivation of penicillin G during experimental infection with Bacteroides fragilis. J Infect Dis. 1978 Apr;137(4):437–442. doi: 10.1093/infdis/137.4.437. [DOI] [PubMed] [Google Scholar]
  17. Sabath L. D. Reappraisal of the antistaphylococcal activities of first-generation (narrow-spectrum) and second-generation (expanded-spectrum) cephalosporins. Antimicrob Agents Chemother. 1989 Apr;33(4):407–411. doi: 10.1128/aac.33.4.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Simpson I. N., Plested S. J., Harper P. B. Investigation of the beta-lactamase stability of ceftazidime and eight other new cephalosporin antibiotics. J Antimicrob Chemother. 1982 May;9(5):357–368. doi: 10.1093/jac/9.5.357. [DOI] [PubMed] [Google Scholar]
  19. Slama T. G., Sklar S. J., Misinski J., Fess S. W. Randomized comparison of cefamandole, cefazolin, and cefuroxime prophylaxis in open-heart surgery. Antimicrob Agents Chemother. 1986 May;29(5):744–747. doi: 10.1128/aac.29.5.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Taylor P. C., Schoenknecht F. D., Sherris J. C., Linner E. C. Determination of minimum bactericidal concentrations of oxacillin for Staphylococcus aureus: influence and significance of technical factors. Antimicrob Agents Chemother. 1983 Jan;23(1):142–150. doi: 10.1128/aac.23.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Täuber M. G., Sande M. A. General principles of therapy of pyogenic meningitis. Infect Dis Clin North Am. 1990 Dec;4(4):661–676. [PubMed] [Google Scholar]
  22. Vogelman B., Gudmundsson S., Leggett J., Turnidge J., Ebert S., Craig W. A. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J Infect Dis. 1988 Oct;158(4):831–847. doi: 10.1093/infdis/158.4.831. [DOI] [PubMed] [Google Scholar]
  23. Zygmunt D. J., Stratton C. W., Kernodle D. S. Characterization of four beta-lactamases produced by Staphylococcus aureus. Antimicrob Agents Chemother. 1992 Feb;36(2):440–445. doi: 10.1128/aac.36.2.440. [DOI] [PMC free article] [PubMed] [Google Scholar]

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