Skip to main content
PMC home page
Postgraduate Medical Journal logoLink to Postgraduate Medical Journal
. 2000 Aug;76(898):479–483. doi: 10.1136/pmj.76.898.479

Pathophysiology of chronic bacterial osteomyelitis. Why do antibiotics fail so often?

J Ciampolini 1, K Harding 1
PMCID: PMC1741709  PMID: 10908375

Abstract

In this review the pathophysiology of chronic bacterial osteomyelitis is summarised, focusing on how bacteria succeed so often in overcoming both host defence mechanisms and antibiotic agents. Bacteria adhere to bone matrix and orthopaedic implants via receptors to fibronectin and to other structural proteins. They subsequently elude host defences and antibiotics by "hiding" intracellularly, by developing a slimy coat, or by acquiring a very slow metabolic rate. The presence of an orthopaedic implant also causes a local polymorphonuclear cell defect, with decreased ability to kill phagocytosed bacteria. Osteolysis is determined locally by the interaction of bacterial surface components with immune system cells and subsequent cytokine production. The increasing development of antibiotic resistance by Staphylococcus aureus and S epidermidis will probably make conservative treatment even less successful than it is now. A close interaction between orthopaedic surgeons and physicians, with combined medical and operative treatment, is to be commended.


Keywords: osteomyelitis; joint replacement infection; antibiotics; osteolysis

Full Text

The Full Text of this article is available as a PDF (149.2 KB).

Selected References

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

  1. Alkan M. L., Beachey E. H. Excretion of lipoteichoic acid by group A streptococci. Influence of penicillin on excretion and loss of ability to adhere to human oral mucosal cells. J Clin Invest. 1978 Mar;61(3):671–677. doi: 10.1172/JCI108979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andriole V. T., Nagel D. A., Southwick W. O. A paradigm for human chronic osteomyelitis. J Bone Joint Surg Am. 1973 Oct;55(7):1511–1515. [PubMed] [Google Scholar]
  3. Baker G. L., Oddis C. V., Medsger T. A., Jr Pasteurella multocida polyarticular septic arthritis. J Rheumatol. 1987 Apr;14(2):355–357. [PubMed] [Google Scholar]
  4. Balwit J. M., van Langevelde P., Vann J. M., Proctor R. A. Gentamicin-resistant menadione and hemin auxotrophic Staphylococcus aureus persist within cultured endothelial cells. J Infect Dis. 1994 Oct;170(4):1033–1037. doi: 10.1093/infdis/170.4.1033. [DOI] [PubMed] [Google Scholar]
  5. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 6-1993. A 69-year-old woman with a sclerotic lesion of the femur and pulmonary nodules. N Engl J Med. 1993 Feb 11;328(6):422–428. doi: 10.1056/NEJM199302113280609. [DOI] [PubMed] [Google Scholar]
  6. Cozens R. M., Tuomanen E., Tosch W., Zak O., Suter J., Tomasz A. Evaluation of the bactericidal activity of beta-lactam antibiotics on slowly growing bacteria cultured in the chemostat. Antimicrob Agents Chemother. 1986 May;29(5):797–802. doi: 10.1128/aac.29.5.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Craigen M. A., Watters J., Hackett J. S. The changing epidemiology of osteomyelitis in children. J Bone Joint Surg Br. 1992 Jul;74(4):541–545. doi: 10.1302/0301-620X.74B4.1624513. [DOI] [PubMed] [Google Scholar]
  8. DUTHIE E. S. The action of fibrinogen on certain pathogenic cocci. J Gen Microbiol. 1955 Oct;13(2):383–393. doi: 10.1099/00221287-13-2-383. [DOI] [PubMed] [Google Scholar]
  9. Dewhirst F. E. N-acetyl muramyl dipeptide stimulation of bone resorption in tissue culture. Infect Immun. 1982 Jan;35(1):133–137. doi: 10.1128/iai.35.1.133-137.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Emslie K. R., Nade S. Acute hematogenous staphylococcal osteomyelitis. A description of the natural history in an avian model. Am J Pathol. 1983 Mar;110(3):333–345. [PMC free article] [PubMed] [Google Scholar]
  11. Espersen F., Clemmensen I. Isolation of a fibronectin-binding protein from Staphylococcus aureus. Infect Immun. 1982 Aug;37(2):526–531. doi: 10.1128/iai.37.2.526-531.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fischer B., Vaudaux P., Magnin M., el Mestikawy Y., Proctor R. A., Lew D. P., Vasey H. Novel animal model for studying the molecular mechanisms of bacterial adhesion to bone-implanted metallic devices: role of fibronectin in Staphylococcus aureus adhesion. J Orthop Res. 1996 Nov;14(6):914–920. doi: 10.1002/jor.1100140611. [DOI] [PubMed] [Google Scholar]
  13. GALLIE W. E. First recurrence of osteomyelitis eighty years after infection. J Bone Joint Surg Br. 1951 Feb;33-B(1):110–111. doi: 10.1302/0301-620X.33B1.110. [DOI] [PubMed] [Google Scholar]
  14. Gallwitz W. E., Mundy G. R., Lee C. H., Qiao M., Roodman G. D., Raftery M., Gaskell S. J., Bonewald L. F. 5-Lipoxygenase metabolites of arachidonic acid stimulate isolated osteoclasts to resorb calcified matrices. J Biol Chem. 1993 May 15;268(14):10087–10094. [PubMed] [Google Scholar]
  15. Haas D. W., McAndrew M. P. Bacterial osteomyelitis in adults: evolving considerations in diagnosis and treatment. Am J Med. 1996 Nov;101(5):550–561. doi: 10.1016/s0002-9343(96)00260-4. [DOI] [PubMed] [Google Scholar]
  16. Hausmann E., Raisz L. G., Miller W. A. Endotoxin: stimulation of bone resorption in tissue culture. Science. 1970 May 15;168(3933):862–864. doi: 10.1126/science.168.3933.862. [DOI] [PubMed] [Google Scholar]
  17. Herrmann M., Vaudaux P. E., Pittet D., Auckenthaler R., Lew P. D., Schumacher-Perdreau F., Peters G., Waldvogel F. A. Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material. J Infect Dis. 1988 Oct;158(4):693–701. doi: 10.1093/infdis/158.4.693. [DOI] [PubMed] [Google Scholar]
  18. Hudson M. C., Ramp W. K., Nicholson N. C., Williams A. S., Nousiainen M. T. Internalization of Staphylococcus aureus by cultured osteoblasts. Microb Pathog. 1995 Dec;19(6):409–419. doi: 10.1006/mpat.1995.0075. [DOI] [PubMed] [Google Scholar]
  19. Ishimi Y., Miyaura C., Jin C. H., Akatsu T., Abe E., Nakamura Y., Yamaguchi A., Yoshiki S., Matsuda T., Hirano T. IL-6 is produced by osteoblasts and induces bone resorption. J Immunol. 1990 Nov 15;145(10):3297–3303. [PubMed] [Google Scholar]
  20. Kaarsemaker S., Walenkamp G. H., vd Bogaard A. E. New model for chronic osteomyelitis with Staphylococcus aureus in sheep. Clin Orthop Relat Res. 1997 Jun;(339):246–252. doi: 10.1097/00003086-199706000-00033. [DOI] [PubMed] [Google Scholar]
  21. Korovessis P., Fortis A. P., Spastris P., Droutsas P. Acute osteomyelitis of the patella 50 years after a knee fusion for septic arthritis. A case report. Clin Orthop Relat Res. 1991 Nov;(272):205–207. [PubMed] [Google Scholar]
  22. Kuusela P. Fibronectin binds to Staphylococcus aureus. Nature. 1978 Dec 14;276(5689):718–720. doi: 10.1038/276718a0. [DOI] [PubMed] [Google Scholar]
  23. Lerner U. H., Sundqvist G., Ohlin A., Rosenquist J. B. Bacteria inhibit biosynthesis of bone matrix proteins in human osteoblasts. Clin Orthop Relat Res. 1998 Jan;(346):244–254. [PubMed] [Google Scholar]
  24. Lopes J. D., dos Reis M., Brentani R. R. Presence of laminin receptors in Staphylococcus aureus. Science. 1985 Jul 19;229(4710):275–277. doi: 10.1126/science.3160113. [DOI] [PubMed] [Google Scholar]
  25. Mackowiak P. A., Jones S. R., Smith J. W. Diagnostic value of sinus-tract cultures in chronic osteomyelitis. JAMA. 1978 Jun 30;239(26):2772–2775. doi: 10.1001/jama.239.26.2772. [DOI] [PubMed] [Google Scholar]
  26. Mahan J., Seligson D., Henry S. L., Hynes P., Dobbins J. Factors in pin tract infections. Orthopedics. 1991 Mar;14(3):305–308. [PubMed] [Google Scholar]
  27. Maxe I., Rydén C., Wadström T., Rubin K. Specific attachment of Staphylococcus aureus to immobilized fibronectin. Infect Immun. 1986 Dec;54(3):695–704. doi: 10.1128/iai.54.3.695-704.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Meghji S., Crean S. J., Nair S., Wilson M., Poole S., Harris M., Henderson B. Staphylococcus epidermidis produces a cell-associated proteinaceous fraction which causes bone resorption by a prostanoid-independent mechanism: relevance to the treatment of infected orthopaedic implants. Br J Rheumatol. 1997 Sep;36(9):957–963. doi: 10.1093/rheumatology/36.9.957. [DOI] [PubMed] [Google Scholar]
  29. Meikle M. C., Gowen M., Reynolds J. J. Effect of streptococcal cell wall components on bone metabolism in vitro. Calcif Tissue Int. 1982 Jul;34(4):350–364. [PubMed] [Google Scholar]
  30. Nair S. P., Meghji S., Wilson M., Nugent I., Ross A., Ismael A., Bhudia N. K., Harris M., Henderson B. Clinical isolates of Staphylococcus aureus have osteolytic surface proteins and a proportion of the population have antibodies that block this activity: is this of prognostic significance? Br J Rheumatol. 1997 Mar;36(3):328–332. doi: 10.1093/rheumatology/36.3.328. [DOI] [PubMed] [Google Scholar]
  31. Nair S. P., Meghji S., Wilson M., Reddi K., White P., Henderson B. Bacterially induced bone destruction: mechanisms and misconceptions. Infect Immun. 1996 Jul;64(7):2371–2380. doi: 10.1128/iai.64.7.2371-2380.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nair S., Song Y., Meghji S., Reddi K., Harris M., Ross A., Poole S., Wilson M., Henderson B. Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity. J Bone Miner Res. 1995 May;10(5):726–734. doi: 10.1002/jbmr.5650100509. [DOI] [PubMed] [Google Scholar]
  33. Norden C. W. Experimental osteomyelitis. I. A description of the model. J Infect Dis. 1970 Nov;122(5):410–418. doi: 10.1093/infdis/122.5.410. [DOI] [PubMed] [Google Scholar]
  34. Norden C. W. Lessons learned from animal models of osteomyelitis. Rev Infect Dis. 1988 Jan-Feb;10(1):103–110. doi: 10.1093/clinids/10.1.103. [DOI] [PubMed] [Google Scholar]
  35. Patti J. M., Boles J. O., Hök M. Identification and biochemical characterization of the ligand binding domain of the collagen adhesin from Staphylococcus aureus. Biochemistry. 1993 Oct 26;32(42):11428–11435. doi: 10.1021/bi00093a021. [DOI] [PubMed] [Google Scholar]
  36. Perry C. R., Pearson R. L., Miller G. A. Accuracy of cultures of material from swabbing of the superficial aspect of the wound and needle biopsy in the preoperative assessment of osteomyelitis. J Bone Joint Surg Am. 1991 Jun;73(5):745–749. [PubMed] [Google Scholar]
  37. Peters G., Locci R., Pulverer G. Adherence and growth of coagulase-negative staphylococci on surfaces of intravenous catheters. J Infect Dis. 1982 Oct;146(4):479–482. doi: 10.1093/infdis/146.4.479. [DOI] [PubMed] [Google Scholar]
  38. Quie P. G., Belani K. K. Coagulase-negative staphylococcal adherence and persistence. J Infect Dis. 1987 Oct;156(4):543–547. doi: 10.1093/infdis/156.4.543. [DOI] [PubMed] [Google Scholar]
  39. Raisz L. G., Alander C., Eilon G., Whitehead S. P., Nuki K. Effects of two bacterial products, muramyl dipeptide and endotoxin, on bone resorption in organ culture. Calcif Tissue Int. 1982 Jul;34(4):365–369. doi: 10.1007/BF02411269. [DOI] [PubMed] [Google Scholar]
  40. Southwood R. T., Rice J. L., McDonald P. J., Hakendorf P. H., Rozenbilds M. A. Infection in experimental hip arthroplasties. J Bone Joint Surg Br. 1985 Mar;67(2):229–231. doi: 10.1302/0301-620X.67B2.3980532. [DOI] [PubMed] [Google Scholar]
  41. Stashenko P., Dewhirst F. E., Peros W. J., Kent R. L., Ago J. M. Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J Immunol. 1987 Mar 1;138(5):1464–1468. [PubMed] [Google Scholar]
  42. Thomson B. M., Mundy G. R., Chambers T. J. Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption. J Immunol. 1987 Feb 1;138(3):775–779. [PubMed] [Google Scholar]
  43. Vaudaux P. E., Waldvogel F. A., Morgenthaler J. J., Nydegger U. E. Adsorption of fibronectin onto polymethylmethacrylate and promotion of Staphylococcus aureus adherence. Infect Immun. 1984 Sep;45(3):768–774. doi: 10.1128/iai.45.3.768-774.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Waldvogel F. A., Medoff G., Swartz M. N. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. N Engl J Med. 1970 Jan 22;282(4):198–206. doi: 10.1056/NEJM197001222820406. [DOI] [PubMed] [Google Scholar]
  45. Wheat L. J., Allen S. D., Henry M., Kernek C. B., Siders J. A., Kuebler T., Fineberg N., Norton J. Diabetic foot infections. Bacteriologic analysis. Arch Intern Med. 1986 Oct;146(10):1935–1940. [PubMed] [Google Scholar]
  46. Zimmerli W., Lew P. D., Waldvogel F. A. Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. J Clin Invest. 1984 Apr;73(4):1191–1200. doi: 10.1172/JCI111305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zimmerli W., Waldvogel F. A., Vaudaux P., Nydegger U. E. Pathogenesis of foreign body infection: description and characteristics of an animal model. J Infect Dis. 1982 Oct;146(4):487–497. doi: 10.1093/infdis/146.4.487. [DOI] [PubMed] [Google Scholar]

Articles from Postgraduate Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES