Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1982 Sep;22(3):461–469. doi: 10.1128/aac.22.3.461

Penetration of cefazolin into normal and osteomyelitic canine cortical bone.

R C Daly, R H Fitzgerald Jr, J A Washington 2nd
PMCID: PMC183766  PMID: 7137985

Abstract

The ability of cefazolin to cross the capillary membrane and its concentrations in the interstitial fluid spaces were studied in normal and osteomyelitic canine bone. The maximum extraction after a single capillary passage and the net extraction after 3 min, determined with triple-tracer indicator-dilution techniques, demonstrated that cefazolin readily traversed the capillaries of normal and osteomyelitic bone. These studies suggest that the altered pathophysiology of osteomyelitic tissue and the complex diffusional characteristics of cefazolin enhanced the ability of this agent to cross the endothelial cells lining the capillaries of osteomyelitic bone. Volume of distribution studies demonstrated that cefazolin was distributed in the plasma and interstitial fluid spaces of normal cortical bone. Although these spaces were increased 330 and 941% in osteomyelitic tissue, the distribution of cefazolin increased proportionally. There was a direct correlation between the calculated concentrations of cefazolin in the interstitial fluid spaces of normal and osteomyelitic cortical bone and the simultaneous serum levels in animals in which a steady-state equilibrium had been achieved. These studies suggest that a physiological barrier or concentration gradient for cefazolin does not exist in normal or osteomyelitic bone. Cefazolin can cross the capillary membranes of bone and achieve bactericidal concentrations in the interstitial fluid space of normal and osteomyelitic tissue.

Full text

PDF
461

Selected References

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

  1. Bassingthwaighte J. B. A concurrent flow model for extraction during transcapillary passage. Circ Res. 1974 Sep;35(3):483–503. doi: 10.1161/01.res.35.3.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bloom J. D., Fitzgerald R. H., Jr, Washington J. A., 2nd, Kelly P. J. The transcapillary passage and interstitial fluid concentration of penicillin in canine bone. J Bone Joint Surg Am. 1980 Oct;62(7):1168–1175. [PubMed] [Google Scholar]
  3. Carbon C., Contrepois A., Brion N., Lamotte-Barrillon S. Penetration of cefazolin, cephaloridine, and cefamandole into interstitial fluid in rabbits. Antimicrob Agents Chemother. 1977 Apr;11(4):594–598. doi: 10.1128/aac.11.4.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cunha B. A., Gossling H. R., Pasternak H. S., Nightingale C. H., Quintiliani R. The penetration characteristics of cefazolin, cephalothin, and cephradine into bone in patients undergoing total hip replacement. J Bone Joint Surg Am. 1977 Oct;59(7):856–859. [PubMed] [Google Scholar]
  5. Davies D. R., Bassingthwaighte J. B., Kelly P. J. Transcapillary exchange of strontium and sucrose in canine tibia. J Appl Physiol. 1976 Jan;40(1):17–22. doi: 10.1152/jappl.1976.40.1.17. [DOI] [PubMed] [Google Scholar]
  6. Dewanjee M. K. Binding of 99mTc ion to hemoglobin. J Nucl Med. 1974 Aug;15(8):703–706. [PubMed] [Google Scholar]
  7. Franson T. R., Edwards L. D., Collins R. F., Root T. E. Cefazolin treatment of bacterial infections. In vitro and in vivo evaluation. Chemotherapy. 1979;25(5):316–325. doi: 10.1159/000237857. [DOI] [PubMed] [Google Scholar]
  8. Kolczun M. C., Nelson C. L., McHenry M. C., Gavan T. L., Pinovich P. Antibiotic concentrations in human bone. A preliminary report. J Bone Joint Surg Am. 1974 Mar;56(2):305–310. [PubMed] [Google Scholar]
  9. Landau Z., Rubinstein E., Halkin H. Interstitial fluid concentrations of cefoxitin, cephazolin and cefamandole. J Antimicrob Chemother. 1980 Sep;6(5):657–663. doi: 10.1093/jac/6.5.657. [DOI] [PubMed] [Google Scholar]
  10. Lee F. H., Pfeffer M., Van Harken D. R., Smyth R. D., Hottendorf G. H. Comparative pharmacokinetics of ceforanide (BL-S786R) and cefazolin in laboratory animals and humans. Antimicrob Agents Chemother. 1980 Feb;17(2):188–192. doi: 10.1128/aac.17.2.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lunke R. J., Fitzgerald R. H., Jr, Washington J. A., 2nd Pharmacokinetics of cefamandole in osseous tissue. Antimicrob Agents Chemother. 1981 May;19(5):851–858. doi: 10.1128/aac.19.5.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moellering R. C., Jr, Swartz M. N. Drug therapy: The newer cephalosporins. N Engl J Med. 1976 Jan 1;294(1):24–28. doi: 10.1056/NEJM197601012940106. [DOI] [PubMed] [Google Scholar]
  13. Morris M. A., Lopez-Curto J. A., Hughes S. P., An K. N., Bassingthwaighte J. B., Kelly P. J. Fluid spaces in canine bone and marrow. Microvasc Res. 1982 Mar;23(2):188–200. doi: 10.1016/0026-2862(82)90064-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Owen M., Triffitt J. T. Extravascular albumin in bone tissue. J Physiol. 1976 May;257(2):293–307. doi: 10.1113/jphysiol.1976.sp011369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Peterson L. R., Gerding D. N. Interaction of cephalosporins with human and canine serum proteins. J Infect Dis. 1978 Apr;137(4):452–457. doi: 10.1093/infdis/137.4.452. [DOI] [PubMed] [Google Scholar]
  16. Peterson L. R., Gerding D. N. Prediction of cefazolin penetration in high- and low-protein-containing extravascular fluid: new method for performing simultaneous studies. Antimicrob Agents Chemother. 1978 Oct;14(4):533–538. doi: 10.1128/aac.14.4.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peterson L. R., Hall W. H., Zinneman H. H., Gerding D. N. Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics. J Infect Dis. 1977 Dec;136(6):778–783. doi: 10.1093/infdis/136.6.778. [DOI] [PubMed] [Google Scholar]
  18. Pitkin D. H., Sachs C., Zajac I., Actor P. Distribution of sodium cefazolin in serum, muscle, bone marrow, and bone of normal rabbits. Antimicrob Agents Chemother. 1977 Apr;11(4):760–762. doi: 10.1128/aac.11.4.760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Quintiliani R., Nightingale C. H. Cefazolin. Ann Intern Med. 1978 Nov;89(5 Pt 1):650–656. doi: 10.7326/0003-4819-89-5-650. [DOI] [PubMed] [Google Scholar]
  20. Rolinson G. N. The significance of protein binding of antibiotics in antibacterial chemotherapy. J Antimicrob Chemother. 1980 May;6(3):311–317. doi: 10.1093/jac/6.3.311. [DOI] [PubMed] [Google Scholar]
  21. Rosdahl V. T., Sørensen T. S., Colding H. Determination of antibiotic concentrations in bone. J Antimicrob Chemother. 1979 May;5(3):275–280. doi: 10.1093/jac/5.3.275. [DOI] [PubMed] [Google Scholar]
  22. Schurman D. J., Hirshman H. P., Burton D. S. Cephalothin and cefamandole penetration into bone, synovial fluid, and wound drainage fluid. J Bone Joint Surg Am. 1980 Sep;62(6):981–985. [PubMed] [Google Scholar]
  23. Schurman D. J., Hirshman H. P., Kajiyama G., Moser K., Burton D. S. Cefazolin concentrations in bone and synovial fluid. J Bone Joint Surg Am. 1978 Apr;60(3):359–362. [PubMed] [Google Scholar]
  24. Schurman D. J., Johnson B. L., Jr, Finerman G., Amstutz H. C. Antibiotic bone penetration. Concentrations of methicillin and clindamycin phosphate in human bone taken during total hip replacement. Clin Orthop Relat Res. 1975 Sep;(111):142–146. [PubMed] [Google Scholar]
  25. Singhvi S. M., Heald A. F., Gadebusch H. H., Resnick M. E., Difazio L. T., Leitz M. A. Human serum protein binding of cephalosporin antibiotics in vitro. J Lab Clin Med. 1977 Feb;89(2):414–420. [PubMed] [Google Scholar]
  26. Singhvi S. M., Heald A. F., Schreiber E. C. Pharmacokinetics of cephalosporin antibiotics: protein-binding considerations. Chemotherapy. 1978;24(3):121–133. doi: 10.1159/000237771. [DOI] [PubMed] [Google Scholar]
  27. Smilack J. D., Flittie W. H., Williams T. W., Jr Bone concentrations of antimicrobial agents after parenteral administration. Antimicrob Agents Chemother. 1976 Jan;9(1):169–171. doi: 10.1128/aac.9.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sørensen T. S., Colding H., Schroeder E., Rosdahl V. T. The penetration of cefazolin, erythromycin and methicillin into human bone tissue. Acta Orthop Scand. 1978 Dec;49(6):549–553. doi: 10.3109/17453677808993236. [DOI] [PubMed] [Google Scholar]
  29. Tan J. S., Salstrom S. J. Levels of carbenicillin, ticarcillin, cephalothin, cefazolin, cefamandole, gentamicin, tobramycin, and amikacin in human serum and interstitial fluid. Antimicrob Agents Chemother. 1977 Apr;11(4):698–700. doi: 10.1128/aac.11.4.698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tetzlaff T. R., Howard J. B., McCraken G. H., Calderon E., Larrondo J. Antibiotic concentrations in pus and bone of children with osteomyelitis. J Pediatr. 1978 Jan;92(1):135–140. doi: 10.1016/s0022-3476(78)80095-x. [DOI] [PubMed] [Google Scholar]
  31. Waterman N. G., Raff M. J., Scharfenberger L., Barnwell P. A. Protein binding and concentrations of cephaloridine and cefazolin in serum and interstitial fluid of dogs. J Infect Dis. 1976 Jun;133(6):642–647. doi: 10.1093/infdis/133.6.642. [DOI] [PubMed] [Google Scholar]

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

RESOURCES