Research Award Details

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Evaluation of deferoxamine impregnated suture as a deterrent to surgical site infection in a rat model

Grant Recipient: Anna Vergun, MD

Co-Investigators:
Institution:
University of North Carolina, Chapel Hill
Presentations & Publications:
Further Funding:
Additional Information:
POSNA Micro Grant Final Report
Evaluation of Deferoxamine Impregnated Suture as a Deterrent to Surgical Site Infection in a Rat Model

Summary:
We examined the effects of deferoxamine (DFO) on the progression of surgical site infection using Staphylococcus aureus in a rat model. Overall, the study was successful in that we tested what we intended to test, the surgical procedure was well tolerated by the animals, and we obtained useable data from our outcome measures. However, given that this was a pilot study testing a previously unexplored application of a compound, the negative results of this study are unlikely to lead to further study on this topic at present. However, we have submitted an abstract to the North Carolina Orthopaedic Association (NCOA) meeting in October 2020. Below is a summary of the project and our findings in abstract form. Thank you to POSNA for funding this investigation.

Abstract:
Deferoxamine has no effect on local angiogenesis or progression of surgical site infection in a rat model
Lukas G. Keil, MD,* Alexis L. Flen, MS,† Thad H. Creech,‡ Paul S. Weinhold, PhD* Anna D. Vergun, MD,*
*Department of Orthopaedics, University of North Carolina School of Medicine, Chapel Hill, NC;
†University of North Carolina School of Medicine, Chapel Hill, NC; ‡University of North Carolina, Chapel Hill, NC
 
Background:
Surgical site infection (SSI) is a potentially morbid complication. Obesity among other factors increases risk for SSI. Deferoxamine (DFO) is an iron chelating agent which has been shown to induce angiogenesis and improve healing when delivered via DFO-soaked suture material. A rat model of SSI using bacteria-soaked multifilament suture is a validated means of evaluating novel treatments for SSI. We hypothesized that DFO-soaked suture would reduce the proliferation and/or deep progression of SSI in a rat model, presumably via angiogenesis, improved perfusion, and increased delivery of immune mediators.

Methods:
This study was funded by a Micro Grant from the Pediatric Orthopaedic Society of North America (POSNA) and approved by the relevant institutional animal care and use committee. Retired-breeder male Sprague Dawley rats were selected as they tend to be overweight, simulating an at-risk population for SSI. A power calculation determined that detecting a 10-fold decrease in CFUs at α=0.05 would require 12 animals for 80% power.

All surgeries were performed on animals from the same supplier by a single surgeon. In each animal a 2cm polyether ether ketone (PEEK) implant was placed just deep to the superficial fascia on both dorsolateral surfaces via separate incisions. After both implants were placed, the fascia of each wound was closed using water-soaked multifilament suture on one wound then DFO-soaked suture on the other, alternating laterality with each animal. After water-tight closure of the fascia of both woundsS, the subcutaneous tissues of both wounds were closed using suture soaked in a fixed volume of Staphylococcus aureus at a set concentration (CFUs/ml) similar to a validated SSI model. In this manner each animal served as its own control. Animals were given analgesics and monitored until euthanasia on post-op day 3.

Following euthanasia, implants were retrieved via new, separate incisions, and wound beds were harvested. Wound beds were split transversely. Cephalad halves were placed in formalin and later stained with hematoxylin and eosin for quantitation of vessel density. PEEK implants and samples of the deep tissue margin of the caudal halves of each wound were placed in containers of sterile culture broth and transferred immediately to the laboratory. Implants and tissue specimens were vortexed and sonicated in culture broth then plated on blood agar using serial dilutions. Colony forming units (CFUs) were counted after 24 hours. Data were analyzed using Chi-square and paired t-tests.

Results:
Two of 12 animals were excluded from analysis: one exclusion was an initial pilot surgery performed differently from the other 11 surgeries, while the other excluded animal had to be euthanized early by veterinary staff for reasons unrelated to infection. Among the remaining 10 animals, the mean animal weight pre-operatively was 511 g (SD 36). Culture of implants yielded non-zero bacterial counts from 0/10 DFO-treated wounds versus 2/10 water-treated wounds (p=0.16). Culture of tissue specimens yielded non-zero bacterial counts from 7/10 DFO-treated wounds versus 8/10 H2O-treated wounds (p=0.32). Pathology specimens demonstrated 6.3 vessels/mm2 (SD 0.7) from DFO-treated wounds versus 6.3 (SD 0.9) from water-treated wounds (p=0.92).

Conclusion:
In this rat model of SSI with DFO-treated suture, DFO failed to demonstrate an effect on either angiogenesis or progression of deep infection at 3 days postoperatively. The absence of a detectable difference in vessel density suggests that 3 days may allow insufficient time to observe any possible effect of DFO on progression of SSI. Future study could investigate the effects of DFO on angiogenesis and progression of SSI over a longer time course.