Grants We Funded

Abstract
Project Summary: Millions of women worldwide have breast implants and bacterial infection remains a primary complication following placement, making breast implant infections a highly relevant aspect of women's health. Importantly, these infections occur despite preventative antibiotic treatment. It is becoming increasingly clear that bacteria form communities (such as biofilms) and gain genetic resistance that provide protection against drug treatment, which are major obstacles to treating bacterial infection with antibiotics. However, how these communities and genes provide protection are still being investigated. Additionally, in the era of antimicrobial stewardship, there has been a major push to use evidence-based medicine when implementing guidelines for the use of prophylactic antibiotics. Thus, this study seeks to determine whether bacteria causing breast implant infection are resistant to typical prophylactic antibiotics given to women receiving implants. It also examines how those bacteria interact with the host during infection to provide recalcitrance to these drugs. We use a multifaceted approach to determine the amount of antibiotic required to kill these bacteria in vitro and in vivo and the changes in gene expression that allow them to initiate and establish infection. In vitro assays will assess whether different types of communities formed by bacteria protect against antimicrobial treatment. An animal model of breast implant infection will be used to assess how effective clinical doses of antibiotics are at clearing infections. Importantly, by combining the animal models with RNA sequencing techniques, these experiments will provide insights into the regulatory pathways and virulence factors bacteria use to interact with the host and avoid being killed by the antibiotics. The results from this project have the potential to provide a better understanding of how bacteria adapt to form hard to treat breast implant infections leading to persistence and recurrence, specifically in the face of antibiotic therapy. These studies will provide the foundation for future studies defining these interactions, which can be used to establish better guidelines for the use of antibiotics in caring for women receiving breast implants or to develop more effective treatment strategies, including non-antibiotic therapeutics. Impact Statement: This study examines how prophylactic antibiotic treatment affects bacteria that cause breast implant infection. We will determine whether breast implant infection isolates are sensitive to common antibiotic pocket irrigants, which will provide direct guidance to physicians for the selection of the most appropriate prophylactic antibiotic. Additionally, this study will provide a better understanding of the host-pathogen interactions that protect bacteria from antibiotics, which may inform the development of effective treatment strategies that prevent breast implant infection and limit the emergence of antibiotic resistance among isolates. This would translate to fewer patient complications, better outcomes that drive improved satisfaction, and de-escalation of healthcare costs.

Biography
I received my undergraduate, medical school and preliminary general surgery training at the University of British Columbia before completing a plastic surgery residency and peripheral nerve research fellowship at Barnes Hospital/Washington University. I have received competitive research awards by the American College of Surgeons and American Association of Plastic Surgeons and was promoted to Professor at Washington University. My research background transitioned from studying nerve regeneration basic science to clinical outcomes research in breast reconstruction and cosmetic surgery, reflecting my clinical practice. My recent studies include a multicenter study, funded by the Plastic Surgery Foundation examining the clinical impact of fat transfer on breast cancer recurrence, and a randomized prospective trial examining the impact of incision location on clinical and patient reported outcomes in women undergoing nipple-sparing mastectomy with implant-based breast reconstruction. A key area of my research is examining the microbiome associated with reconstructive and cosmetic breast implants. I reported on the diverse microbiome causing breast implant infections at our facility and studied the impact of acellular dermal matrices on bacterial biofilms in reconstructive breast implant surgery. I have established a collaboration with Dr. Scott Hultgren, a world-expert in infectious disease in women, here at Washington University to advance this field in plastic surgery.