Antimicrobial Efficacy Studies

In Vivo Model of Human Pathogen Infection and Demonstration of Efficacy by an Antimicrobial Pouch for Pacing Devices

Linda K. Hansen, Ph.D.¹, Mary Brown¹, David Johnson¹, Donald F. Palme, II, Ph.D.¹,
Charles Love, M.D.², and Rabih Darouiche, M.D.³
WuXi AppTec, Inc., St. Paul, MN 55120

ABSTRACT

Background: Device-related infections represent a significant clinical challenge. Once established, these infections prove difficult to treat with existing antibiotic regimens, compromising the health of device recipients, and usually requiring surgical intervention to resolve.

Objective: The purpose of this study was to determine the efficacy of the AIGISRX™ Anti-Bacterial envelope designed to reduce device-related infections by incorporating minocycline and rifampin in a controlled release polymer. Methods: An infection was established in a rabbit model by creating bilateral subcutaneous implant pockets, into which a pacing device with or without AIGISRX™ was placed. The incisions were closed, and a defined dose of bacteria was infused into each implant pocket. After seven days, devices were explanted and sampled for viable bacteria by swabbing and sonication.

Results: Initial studies evaluated the ability of the AIGISRX pouch to reduce Staphylococcus epidermidis infection in this model using clinical and quantitative microbial endpoints. Results demonstrate Staphylococcus epidermidis infection in all control samples, while no pathogens were recovered from samples with the AIGISRX™ pouch. Systemic antibiotic levels were undetectable. Additional studies tested the efficacy of the AIGISRX™ pouch with additional bacterial strains, Staphylococcus capitis, Escherichia coli, and Acinetobacter Baumannii. In each case the device and implant pocket with the AIGISRX™ pouch was free of any signs of infection. An assessment of biofilm produced by Acinetobacter demonstrated the elimination of biofilm formation on the implanted device. Conclusion: These results demonstrate that in this animal model, the AIGISRX™ device reduces the risk for infection of viable pathogens within implant pockets.

1 WuXi AppTec, Inc., St. Paul, MN 55120
2 Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH 43210
3 Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030
The testing presented in this manuscript was sponsored by TyRx Pharma, Inc., manufacturer of the AIGISRX™ product.