Skip to main content
SpringerLink
Log in

Topical vancomycin for treatment of methicillin-resistant Staphylococcus epidermidis infection in a rat spinal implant model

  • Basic Science
  • Published:
Spine Deformity Aims and scope Submit manuscript

Abstract

Study design

Basic science.

Objective

Investigate the ability of local applicaiton of vancomycin, either in powder form or suspended within poly(lactic-co-glycolic acid) microspheres (MS), to treat infection using a rat spinal model.

Summary of background data

Surgical site infections (SSIs) are a serious complication after spine surgery and are associated with high morbidity and mortality and often caused my coagulase negative staphylococci. A comprehensive approach to reduce SSIs has been recommended including the use of topical vancomycin. Animal and human studies have shown improved control of infection with local compared to systemic antibiotics.

Methods

K-wires seeded with methicillin-resistant Staphylococcus epidermidis RP62A (MRSE) were treated with vancomycin powder, carboxymethylcellulose sodium salt (CMC) (microsphere carrier), vancomycin powder, blank MS or vancomycin-loaded MS for 24 or 48 h in vitro after which bacteria were enumerated. In addition, a spinal instrumentation model was developed in rats with a bacterial seeded K-wire implanted into the right side of L4 and L5. Rats underwent no treatment or were treated locally with either vancomycin powder, blank MS or vancomycin-loaded MS. After 8 weeks, the K-wire, bone, soft tissue and wire fastener were cultured and results analyzed.

Results

Vancomycin powder and vancomycin-loaded MS resulted in significantly fewer bacteria remaining in vitro than did CMC. Vancomycin powder- treated animals’ cultures were significantly lower than all other groups (P < 0.0001) with negative culture results, except for one animal. The vancomycin-loaded MS-treated animals had lower bone bacterial counts than the controls (P < 0.0279); blank MS-treated animals had no differences in bacterial densities when compared to non-treated animals.

Conclusion

Vancomycin powder and vancomycin-loaded MS were active against MRSE in vitro, in a rat MRSE implant model; however, vancomycin MS were inferior to the topical vancomycin powder. Vancomycin powder prevented MRSE infection in a rat spinal implant 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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Hey HWD, Thiam DW, Koh ZSD et al (2017) Is intraoperative local vancomycin powder the answer to surgical site infections in spine surgery? Spine 42:267–274

    Article  Google Scholar 

  2. Lee GI, Bak KH, Chun HJ et al (2016) Effect of using local intrawound vancomycin powder in addition to intravenous antibiotics in posterior lumbar surgery: midterm result in a single-center study. Korean J Spine 13:47

    Article  Google Scholar 

  3. Agarwal N, Agarwal P, Querry A et al (2018) Implementation of an infection prevention bundle and increased physician awareness improves surgical outcomes and reduces costs associated with spine surgery. J Neurosurg 29:108–114

    Google Scholar 

  4. Vitale MG, Riedel MD, Glotzbecker MP et al (2013) Building consensus: development of a best practice guideline (BPG) for surgical site infection (SSI) prevention in high-risk pediatric spine surgery. J Pediatr Orthop 33:471–478

    Article  Google Scholar 

  5. Gerometta A, Olaverri JCR, Bitan F (2012) Infections in spinal instrumentation. Int Orthop 36:457–464

    Article  Google Scholar 

  6. Kang DG, Holekamp TF, Wagner SC et al (2015) Intrasite vancomycin powder for the prevention of surgical site infection in spine surgery: a systematic literature review. Spine J 15:762–770

    Article  Google Scholar 

  7. Park HY, Sheppard W, Smith R et al (2018) The combined administration of vancomycin IV, standard prophylactic antibiotics, and vancomycin powder in spinal instrumentation surgery: does the routine use affect infection rates and bacterial resistance? J Spine Surg 4:173

    Article  Google Scholar 

  8. Takeuchi M, Wakao N, Kamiya M et al (2018) A double-blind randomized controlled trial of the local application of vancomycin versus ampicillin powder into the operative field for thoracic and/or lumbar fusions. J Neurosurg Spine 1:1–7

    Google Scholar 

  9. Texakalidis P, Lu VM, Yolcu Y et al (2018) Impact of powdered vancomycin on preventing durgical dite infections in neurosurgery: a systematic review and meta-analysis. Neurosurg 84:569–580

    Article  Google Scholar 

  10. Xie LL, Zhu J, Yang MS et al (2017) Effect of intra-wound vancomycin for spinal surgery: a systematic review and meta-analysis. Orthop Surg 9:350–358

    Article  Google Scholar 

  11. Clark A, Milbrandt TA, Hilt JZ et al (2014) Retention of insulin-like growth factor I bioactivity during the fabrication of sintered polymeric scaffolds. Biomed Mater 9:025015

    Article  Google Scholar 

  12. Raiche A, Puleo D (2006) Modulated release of bioactive protein from multilayered blended PLGA coatings. Int J Pharm 311:40–49

    Article  CAS  Google Scholar 

  13. Hu Y, Hegde V, Johansen D et al (2017) Combinatory antibiotic therapy increases rate of bacterial kill but not final outcome in a novel mouse model of Staphylococcus aureus spinal implant infection. PLoS ONE 12:e0173019

    Article  Google Scholar 

  14. Brown ME, Zou Y, Peyyala R et al (2018) Testing of a bioactive, moldable bone graft substitute in an infected, critically sized segmental defect model. J Biomed Mater Res B 106:1878–1886

    Article  CAS  Google Scholar 

  15. Liu G, Chen S, Fang J et al (2016) Vancomycin microspheres reduce postoperative spine infection in an in vivo rabbit model. BMC Pharmacol Toxicol 17:61

    Article  Google Scholar 

  16. Andersen NJ (2014) Microsphere spray system for wound coverage. Thesis, Biomedical Engineering, University of Kentucky

  17. Armaghani SJ, Menge TJ, Lovejoy SA et al (2014) Safety of topical vancomycin for pediatric spinal deformity: nontoxic serum levels with supratherapeutic drain levels. Spine 39:1683–1687

    Article  Google Scholar 

  18. Miksić NG (2013) Spinal infections with and without hardware: the viewpoint of an infectious disease specialist. Eur J Orthop Surg Traumatol 23:21–28

    Article  Google Scholar 

Download references

Acknowledgements

Mayo Clinic Endowment for Pediatric Infectious Diseases. We would like to acknowledge Scott Gamb (Mayo Clinic) for performing biofilm imaging. IRB approval was not necessary for this study. Level 2 FDA approved.

Funding

There was no outside funding for this study. No funding was received from the National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI).

Author information

Authors and Affiliations

  1. Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA

    Melissa J. Karau & Robin Patel

  2. Division of Pediatric Orthopedic Surgery, Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN, 55905, USA

    Chenghao Zhang, Andre J. van Wijnen, A. Noelle Larson & Todd A. Milbrandt

  3. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA

    Jayawant N. Mandrekar

  4. Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA

    Robin Patel

  5. F. Joseph Halcomb III Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA

    Nicholas J. Kohrs

  6. Department of Biomedical Engineering, University of Mississippi, Oxford, MS, USA

    David A. Puleo

  7. Department of Pediatrics, Division of Infectious Diseases and Immunology, Levine Children’s Hospital, Charlotte, NC, USA

    Thomas G. Boyce

  8. Division of Orthopaedics, Mayo Clinic, 200 First St S.W., Rochester, MN, 55905, USA

    Todd A. Milbrandt

Authors
  1. Melissa J. Karau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chenghao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jayawant N. Mandrekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicholas J. Kohrs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David A. Puleo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andre J. van Wijnen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robin Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thomas G. Boyce
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Noelle Larson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Todd A. Milbrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MJK: experimental design, execution, data analysis, drafting manuscript and review and approval of manuscript. CZ: experimental design, execution, drafting portions of the manuscript and review of manuscript and approval of manuscript. JNM: experimental design and statistical analysis of data, manuscript review and approval of manuscript. NJK: manufacturing and analyzing the release of vancomycin-loaded PLGA microspheres, drafting portions of the manuscript and manuscript review and approval of manuscript. DAP: oversight of the manufacturing and analyzing the release of vancomycin-loaded PLGA microspheres, drafting portions of the manuscript and manuscript review and approval of manuscript. AJvW, TGB, and ANL: experimental design and manuscript review and approval of manuscript. RP: co-investigator, experimental design, oversight of execution and manuscript review and approval of manuscript. TAM: principal investigator, experimental design, oversight of execution and manuscript review and approval of manuscript.

Corresponding author

Correspondence to Todd A. Milbrandt.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karau, M.J., Zhang, C., Mandrekar, J.N. et al. Topical vancomycin for treatment of methicillin-resistant Staphylococcus epidermidis infection in a rat spinal implant model. Spine Deform 8, 553–559 (2020). https://doi.org/10.1007/s43390-020-00087-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43390-020-00087-4

Keywords

Search

Navigation