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Chitosan Sponges for Local Synergistic Infection Therapy: A Pilot Study

  • Symposium: 2012 Musculoskeletal Infection Society
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Although bacterial antibiotic resistance is increasing, fewer new antibiotics are being developed to compensate. Localized delivery of synergistic antiseptics and antibiotics with a chitosan sponge device may offer an alternative infection treatment.

Questions/purposes

In this pilot study, we asked whether antiseptic and antibiotic combinations provided in vitro synergism against Staphylococcus aureus, whether synergism reduces cell viability, and whether their combination releases drugs at inhibitory levels.

Methods

To investigate the pharmacodynamics among three combinations of the antiseptic chlorhexidine digluconate (CHX) with the antibiotics amikacin, daptomycin, and vancomycin (VAN) (n = 1), we determined the fractional inhibitory concentration (FIC) index against S aureus Cowan I. The determined synergistic combination of CHX and VAN was evaluated for cell compatibility using NIH/3T3 fibroblasts (n = 3) and the drug release profile from a chitosan sponge device (n = 5).

Results

With an FIC index < 0.5, the combination of CHX + VAN exhibited synergism against S aureus. CHX concentrations ≥ 3.91 μg/mL resulted in fibroblast viability decrease, whereas the combination of CHX + VAN did not decrease fibroblast viability until their concentrations reached ≥ 7.81 μg/mL. The CHX and VAN release profile, both individually and in combination, was an initial bolus with no difference between eluate concentrations after Day 5.

Conclusions

CHX + VAN combination may be delivered locally by a chitosan sponge that synergistically inhibits S aureus growth.

Clinical Relevance

The use of synergism between combined antibiotic and antiseptics delivered at high local concentrations with an implanted chitosan sponge may provide a useful alternative infection treatment option.

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Acknowledgments

We thank Cubist Pharmaceuticals (Lexington, MA, USA) for their donation of the daptomycin used in this investigation.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Memphis, 328A Engineering Technology Building, Memphis, TN, 38152, USA

    J. Keaton Smith MS, Abteen R. Moshref BS, Jessica A. Jennings PhD & Warren O. Haggard PhD

  2. Veterans Affairs Medical Center and University of Tennessee Health Science Center, Memphis, TN, USA

    Harry S. Courtney PhD

Authors
  1. J. Keaton Smith MS
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  2. Abteen R. Moshref BS
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  3. Jessica A. Jennings PhD
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  4. Harry S. Courtney PhD
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Corresponding author

Correspondence to J. Keaton Smith MS.

Additional information

One or more of the authors (WOH) has received funding from the National Institutes of Health (R01 AI06907-02) and the NSF GRFP. One of the authors (WOH) receives royalties from Bionova Medical (Germantown, TN, USA). One of the authors (WOH) has received funding from US Army OETRP and Advanced Technology Grants, Cubist Pharmaceuticals (Lexington, MA, USA) material/research support.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

This work was performed at the University of Memphis and the Veterans Affairs Medical Center, Memphis, TN, USA.

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Smith, J.K., Moshref, A.R., Jennings, J.A. et al. Chitosan Sponges for Local Synergistic Infection Therapy: A Pilot Study. Clin Orthop Relat Res 471, 3158–3164 (2013). https://doi.org/10.1007/s11999-013-2988-5

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  • DOI: https://doi.org/10.1007/s11999-013-2988-5

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