Skip to main content

Advertisement

SpringerLink
Log in

Local Delivery of Vancomycin for the Prophylaxis of Prosthetic Device-Related Infections

  • Research Papers
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

No Heading

Purpose.

To evaluate the in vivo efficacy and pharmacokinetics of vancomycin delivered from glycerylmonostearate (GMS) implants in a prosthetic-device based biofilm infection model.

Methods.

A biofilm infection model was developed in male Sprague-Dawley rats by implanting a vascular graft on the dorsal side of each rat and infecting it with 1.5 × 108 cfu/ml Staphylococcus epidermidis. The rats were divided into 3 groups of 6 rats each: 1) the control group that received no antibiotics, 2) the IM group that received multiple IM injections of vancomycin at a dose of 25 mg/kg every 6 h for a total of 12 doses, and 3) the implant group that received GMS implants designed to deliver vancomycin at a total dose of 300 mg/kg for a period of 4 days. The pharmacokinetics of vancomycin was determined from IM and implant groups by analyzing for vancomycin in blood using HPLC. In vivo efficacy was studied by evaluation of the wound site and the prosthetic device upon excision, for evidence of infection in the form of purulent discharge at the wound site and yellowish discoloration of the prosthetic device and inflammation as sign of biofilm formation. Microbiological evaluation on the wound site and the prosthetic device was performed by culturing the swabs at the wound site and the prosthetic device in sterile tryptic soy broth for 36–48 h at 37°C.

Results.

Vancomycin was successfully delivered in a sustained manner for 100 h from GMS implants and the resulting plasma profile showed that the concentrations, after an initial burst, plateaued at about of 4.77 ± 1.43 μg/ml with less fluctuations than the IM group in which the plasma concentrations fluctuated between 2.73 ± 0.94 μg/ml and 19.26 ± 3.67 μg/ml. Upon excision of the wound site, all the animals in the control group developed infection in the form of purulent discharge and yellowish discoloration of the prosthetic device. However, none of the rats in the implant group showed evidence of infection clearly demonstrating the efficacy of the local delivery system in preventing infection. Systemically delivered vancomycin by IM injections failed to prevent infection in four out of six rats. Microbiological evaluation of the wound site and prosthetic device resulted in isolation of biofilm-producing organisms such as Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus. These organisms were isolated in greater number of animals in the control group compared to the IM and implant groups.

Conclusions.

The GMS implants as a delivery system for vancomycin were successful in preventing infection in all the animals compared to the IM and control groups demonstrating the efficacy of a local delivery system in a prosthetic device related biofilm infection model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 1. R. Langer and D. A. Tirrell. Designing materials for biology and medicine. Nature 428:487–492 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. 2. W. Zimmerli and F. A. Waldvogel. Models of foreign-body infections. In O. Zak and M. A. Sande, (eds.), Experimental Models in Antimicrobial Chemotherapy, 1986, 1, Academic Press, London, UK, pp. 295–317.

    Google Scholar 

  3. 3. M. Dickinson and A. L. Bisno. Infections associated with indwelling implants: concepts of pathogenesis; infections associated with intravascular implants. Antimicrob. Agents Chemother. 33:597–601 (1989).

    CAS  PubMed  Google Scholar 

  4. 4. C. Potera. Biofilms invade microbiology. Science 273:1795–1797 (1996).

    CAS  PubMed  Google Scholar 

  5. 5. F. A. Waldvogel, P. E. Vaudaux, D. Pittet, and P. D. Lew. Perioperative antibiotic prophylaxis of wound and foreign body infections: microbial factors affecting efficacy. Rev. Infect. Dis. 13:S782–S789 (1991).

    CAS  PubMed  Google Scholar 

  6. 6. J. Costerton. Overview of microbial biofilms. J. Ind. Microbiol. 15:137–140 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. 7. T. Jouenne, O. Tresse, and J. Junter. Agar-entrapped bacteria as an in vitro model of biofilms and their susceptibility to antibiotics. FEMS Microbiol. Lett. 119:237–242 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. 8. M. R. W. Brown and P. Gilbert. Sensitivity of Biofilms to antimicrobial agents, J. Applied Bacteriol. Symp. Suppl. 74:87S–97S (1993).

    Google Scholar 

  9. 9. J. C. Nickel, I. Ruseska, I. B. Wright, and J. B. Costerton. Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material. Antimicrob. Agents Chemother. 27:619–624 (1985).

    CAS  PubMed  Google Scholar 

  10. 10. J. W. Costerton. The Etiology and persistence of cryptic bacterial infections: a hypothesis. Rev. Infect. Dis. 6:S606–S618 (1984).

    Google Scholar 

  11. 11. M. R. Weitekamp and G. M. Caputo. Antibiotic prophylaxis: update on common clinical uses. Am. Fam. Physician 48:597–604 (1993).

    CAS  PubMed  Google Scholar 

  12. 12. K. Adams, L. Couch, G. Cierny, J. Calhoun, and J. T. Mader. In vitro and In vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin. Orthoped. Rel. Res. 278:244–252 (1992).

    Google Scholar 

  13. 13. K. J. Wilson, G. Cierny, K. R. Adams, and J. T. Mader. Comparative evaluation of the diffusion of tobramycin and cefotaxime out of antibiotic-impregnated polymethylmethacrylate beads. J. Orthop. Res. 6:279–286 (1988).

    CAS  PubMed  Google Scholar 

  14. 14. K. Adams, L. Couch, G. Cierny, J. Calhoun, and J. T. Mader. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin. Orthop. Rel. Res. 278:244–252 (1992).

    Google Scholar 

  15. 15. J. C. Calhoun and J. T. Mader. Antibiotic beads in the management of surgical infections. Am. J. Surg. 157:443–449 (1989).

    CAS  PubMed  Google Scholar 

  16. 16. C. T. Laurencin, T. Gerhart, P. Witschger, R. Satcher, A. Domb, A. E. Rosenberg, P. Hanff, L. Edsberg, W. Hayes, and R. Langer. Bioerodible polyanhydrides for antibiotic drug delivery: in vivo osteomyelitis treatment in a rat model system. J. Orthop. Res. 11:627–632 (1993).

    PubMed  Google Scholar 

  17. 17. G. Wei, Y. Kotoura, M. Oka, T. Yamamuro, R. Wada, S. Hyon, and Y. Ikada. A bioabsorbable delivery system for the treatment of osteomyelitis. J. Bone Joint Surgery 73-B:246–252 (1991).

    Google Scholar 

  18. 18. S. Allababidi and J. C. Shah. Efficacy and pharmacokinetics of site-specific cefazolin delivery using biodegradable implants in the prevention of post-operative wound infections. Pharm. Res. 15:325–333 (1998).

    CAS  PubMed  Google Scholar 

  19. 19. K. A. Rodovald. Therapeutic considerations for infections caused by Staphylococcus epidermidis. Pharmacotherapy 8:14S–19S (1988).

    PubMed  Google Scholar 

  20. 20. D. M. Chilukuri and J. C. Shah. In vitro release kinetics and mechanism of vancomycin release from GMS implants for the prophylaxis of prosthetic device related infections. Pharm. Res. 15:S96 (1998).

    Google Scholar 

  21. 21. J. Luska and A. Marusic. Rapid high-performance liquid chromatographic determination of vancomycin in human plasma. J. Chromat. B 667:277–281 (1995).

    Google Scholar 

  22. 22. J. G. Wagner and E. Nelson. J. Pharm. Sci. 53:1392–1403 (1964).

  23. 23. T. D. Sanford and E. D. Colby. Effect of xylazine and ketamine on blood pressure, heart rate, and respiratory rate in rabbits. Lab. Anim. Sci. 30:519–523 (1980).

    CAS  PubMed  Google Scholar 

  24. 24. R. O. Darouiche, A. Dhir, A. J. Miller, G. C. Landon, I. I. Raad, and D. M. Musher. Vancomycin penetration into biofilm covering infected prosthesis and effect on bacteria. J. Infect. Dis. 170:720–723 (1994).

    CAS  PubMed  Google Scholar 

  25. 25. S. Schwank, Z. Rajacic, W. Zimmerli, and J. Blaser. Impact of bacterial biofilm formation on in vitro and in vivo activities of antibiotics. Antimicrob. Agents Chemother. 42:895–898 (1998).

    CAS  PubMed  Google Scholar 

  26. 26. G. D. Christensen, W. A. Simpson, A. L. Bisno, and E. H. Beachey. Experimental foreign body infections in mice challenged with slime producing Staphylococcus epidermidis. Infection and Immunity, 40(1):407–410 (1983).

    CAS  PubMed  Google Scholar 

  27. 27. T. M. Bergamini, T. M. McCurry, J. D. Bernard, K. L. Hoeg, R. A. Corpus, J. C. Peyton, K. R. Brittain, and W. G. Cheadle. Antibiotic efficacy against Staphylococcus epidermidis adherent to vascular grafts. J. Surg. Res. 60:3–6 (1996).

    CAS  PubMed  Google Scholar 

  28. 28. A. B. Kaiser. Antimicrobial prophylaxis in surgery. Medical Intelligence 315:1129–1138 (1986).

    CAS  Google Scholar 

  29. 29. A. E. Khoury, K. Lam, B. Ellis, and J. W. Costerton. Prevention and control of bacterial infections associated with medical devices. ASAIO Journal 38(3):M174–M178 (1992).

    CAS  PubMed  Google Scholar 

  30. 30. G. Wang, S. Liu, S. W. Ueng, and E. Chan. The release of cefazolin and gentamicin from biodegradable PLA/PGA beads. Int. J. Pharmaceutics 273:203–212 (2004).

    CAS  Google Scholar 

  31. 31. M. L. Zeckel and J. R. Woodworth. Vancomycin, A Clinical Overview in Glycopeptide Antibiotics, Ramakrishnan Nagarajan, (ed.), Glycopeptide Antibiotics, Marcel Dekker, New York, 1994, pp. 309–412.

    Google Scholar 

  32. 32. M. McGuckin. MRSA and VRSA in wound care: accept the challenge. Adv. Skin Wound Care 17:93–95 (2004).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Office of Clinical Pharmacology and Biopharmaceutics, U.S. Food and Drug Administration, Rockville, Maryland, 20850, USA

    Dakshina M. Chilukuri

  2. Pharmaceutical R & D, Pfizer Global R&D, Groton, Connecticut, 06340, USA

    Jaymin C. Shah

Authors
  1. Dakshina M. Chilukuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jaymin C. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dakshina M. Chilukuri.

Additional information

This manuscript represents the personal opinion of the author and does not necessarily represent the views or policies of the Food and Drug Administration.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chilukuri, D., Shah, J. Local Delivery of Vancomycin for the Prophylaxis of Prosthetic Device-Related Infections. Pharm Res 22, 563–572 (2005). https://doi.org/10.1007/s11095-005-2497-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-005-2497-7

Key words:

Search

Navigation