Copyright © 2007 by The Journal of Bone and Joint Surgery, Inc.
Commentary & Perspective
Commentary & Perspective by
Jason H. Calhoun, MD*,
University of Missouri-Columbia, Columbia, Missouri
Posted May 2007
The authors made use of a rat model to investigate an alternative to the use of standard perioperative systemic antibiotics for the prevention of surgical wounds. Their hypothesis was that a sustained release of local antibiotics in the wound cavity would be more effective than the use of systemic antibiotics. Instead, the authors found that gentamicin-loaded calcium sulfate flakes did not significantly lower bacteria counts when compared with systemic administration of gentamicin, but they did note that an injection of gentamicin solution directly into the closed wound significantly lowered bacteria levels compared with systemic treatment (p = 0.0003).
This well-written and well-researched study will be a valuable addition to the growing body of work focused on improved methods of local antibiotic delivery through bioabsorbable substances. The fact that the authors found that direct injection of antibiotic was more effective than implantation in a rat model is not a big surprise, but their published observation of a side-by-side comparison is of value. I would like to share the following seven observations:
1. The authors wisely refrain from directly translating the results from a rat model to humans and instead recommend research in larger animals as a step toward controlled human studies.
2. In some treatment groups, the authors used a small volume (0.5 mL) of saline irrigant and allowed it to run out of the wound. Although it was not the goal of the authors to simulate surgical irrigation, this similar effect should be noted by readers who may wish to design a similar study. (The irrigant volume was based on the amounts that had resulted in consistent infections in the pilot studies.)
3. As noted in the article, the danger associated with local delivery of large doses of gentamicin is tissue toxicity, leading to cell death and possibly inhibition of healing. The dosage used in this study is higher than the levels that were identified by Miclau et al. as leading to cell death1. Again, the authors recognize the problem, citing previous works that demonstrate how antibiotic levels should drop rapidly in the injection model, but this question will be a primary source of concern in any larger study or trial.
4. The authors chose gentamicin because they were testing their hypothesis against a strain of Staphylococcus aureus that was sensitive to that antibiotic. I am intrigued, however, by their suggestion that a combination of systemic cephalosporin therapy and local administration of gentamicin may be more effective than the gentamicin-only therapy used in the present study. This is an interesting hypothesis.
5. Despite the lack of efficacy demonstrated by the calcium sulfate "flakes" loaded with gentamicin (compared with direct injection), there is good evidence that gentamicin-impregnated hydroxyapatite beads are effective in open fractures2-5. More recent studies, including one in a rat model, of devices for the controlled release of gentamicin sulfate, are very promising6.
6. There is a full log difference between the systemic gentamicin and local gentamicin groups, and perhaps, with a larger sample size, the authors would have been able to show significance. On the other hand, a higher concentration of gentamicin may have the same effect.
7. There was no polymethylmethacrylate control wing in the study.
In all, I believe the authors offer some valuable observations in a continually evolving area of investigation. They do not just attempt to answer important questions but raise others, and I congratulate them on their good work.
*The author did not receive any outside funding or grants in support of his research for or preparation of this work. Neither he nor a member of his immediate family received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the author, or a member of his immediate family, is affiliated or associated.
References
1. Miclau T, Edin ML, Lester GE, Lindsey RW, Dahners LE. Bone toxicity of locally applied aminoglycosides. J Orthop Trauma. 1995;9:401-6.
2. Henry SL, Ostermann PA, Seligson D. The prophylactic use of antibiotic impregnated beads in open fractures. J Trauma. 1990;30:1231-8.
3. Henry SL, Ostermann PA, Seligson D. The antibiotic bead pouch technique. The management of severe compound fractures. Clin Orthop Relat Res. 1993;295:54-62.
4. Ostermann PA, Seligson D, Henry SL. Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases. J Bone Joint Surg Br. 1995;77:93-7.
5. Moehring HD, Gravel C, Chapman MW, Olson SA. Comparison of antibiotic beads and intravenous antibiotics in open fractures. Clin Orthop Relat Res. 2000;372:254-61.
6. Krasko MY, Golenser J, Nyska A, Nyska M, Brin YS, Domb AJ. Gentamicin extended release from an injectable polymeric implant. J Control Release. 2007;117:90-6.
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