A critical analysis of irrigation solutions in breast surgery

Introduction

Breast implants remain the most commonly implantable medical devices in plastic surgery operating rooms. In 2019 nearly 300,000 women and in 2020, despite the COVID-19 pandemic, 200,000 women underwent cosmetic breast augmentation in the US. Breast implants also represent the most common form of post-mastectomy reconstruction for the 1 in 8 women in the US who will be diagnosed with breast cancer during their lifetimes. , Limiting infections that cause failed breast reconstructions, and preventing capsular contractures that require reoperation on cosmetic or reconstructive breast implants, are a focus of ongoing research that aims to optimize breast implant surgery. Subclinical infection and biofilm formation have been implicated in the formation of capsular contracture, and even more recently investigated as a potential link to breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). In this chapter, we will describe the evolution of antibiotic irrigation practice, review the efficacy of the common antibiotic solutions, and provide up-to-date evidence-based guidelines for its use.

The breast is a clean-contaminated site

The breast is an ectodermally-derived skin appendage that consists of parenchymal and stromal components. The parenchyma forms a system of branching ducts that provide direct passageway between the breast stroma and glandular tissue and the overlying skin. Much like the importance of the intestinal microbiome, the breast microbiome contributes to the maintenance of healthy breast tissue. The breast tissue is home to a diverse endogenous flora that arises from the complex ductal system, which has led to the breast being described as a “clean-contaminated” site. Surgical manipulation of breast tissue with subsequent tissue edema, ductal manipulation, and foreign body insertion can alter the homeostatic equilibrium of the breast microbiome, resulting in increased risk of opportunistic infections. The infection rates following breast surgery ranges from 3% to 15%, while the infection rates after clean surgery is much lower, ranging from 1.5% to 3 %. Therefore, characterization of the breast microbiota is essential when choosing optimal intra-operative antibiotic treatment to prevent postoperative infections related to breast manipulation.

Thornton et al . were the first to explore the anaerobic, aerobic, and fungal flora of the human breast. Cultures of breast biopsy specimens resembled the composition of skin flora, with coagulase negative staphylococcus and anaerobic Propionibacterium acnes resulting in the most growth. This was expanded upon by future reports, which further characterized the breast microbiome in relation to breast region, implant placement, and propensity for infection. Tissue samples taken from different sites of the breast harbor a significant difference in the positive culture rate among all three sites, with highest quantitative bacterial counts in the concentrated ductal tissue of the periareolar region. Despite the difference in quantity, Staphylococcus epidermidis and Propionibacterium acnes remain the most commonly identified organisms in all breast regions.

It will come as no surprise that the most common postoperative breast infections are caused by organisms frequently found within the breast microbiota. Six causative organisms are predominantly involved in implant-related infections: Staphylococcus epidermidis , Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , Propionibacterium acnes , and Corynebacterium spp., each of which are documented as common breast flora. Other more recently documented infectious agents include Serratia spp.,  Enterococcus spp., Enterobacter spp., group B Streptococcus spp., and Morganella spp. In addition to causing acute infections, many of these problematic strains have developed methods to adhere to implant surfaces, forming assemblages of surface-adherent bacteria encapsulated in extracellular polymers known as biofilms. The formation of these biofilms around an implant are implicated in subclinical infections, capsular contracture, and other systemic symptoms. Breast pocket antibiotic irrigation is a common clinical practice that aims to minimize the risk of contamination from breast flora.

Biofilms and breast implants

A biofilm is a complex microbial community of cells that is permanently attached to a substrate through a complex extracellular polymeric matrix they produce. Biofilm production is initiated by bacterial attachment to a surface, followed by cell-to-cell adhesion, extracellular matrix secretion, and bacterial multiplication on the synthetic material. The bacterial-derived extracellular matrix serves as a shelter for the host bacteria, resulting in protection from the host immune response. Bacteria within biofilms also display unique phenotypic differences in comparison to their planktonic states that further bolster antibiotic and host immune response resistance. For example, the two most commonly identified bacteria in breast capsules, Staphylococcus aureus and Staphylococcus epidermidis , have been shown to augment secretion of pyrazinones in the biofilm state, altering the innate immune response and facilitating colonization.

The first step to biofilm formation is mediated through expression and coordination of specific adhesins, which mediate adherence to bacterial-synthesized extracellular substances. In staphylococci biofilms, cell wall-anchored adhesins bind to polymer of β-1,6-linked N-acetylglucosamine (PIA), whose synthesis is mediated by the ica operon. In a similar manner, a highly studied family of these adhesins known as microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) are capable of interacting with host proteins. Studies have demonstrated conserved carriage of MSCRAMMs SdrF in S. epidermidis isolates, which binds to host type I collagen and enables formation of dense, organized biofilms.

Biofilm formation around medical implants is pervasive and is associated with significant morbidity and mortality. In implant-based breast operations, the endogenous breast flora is exposed to the implant during placement. Bacteria adhere to the implant surface using the methods previously described and initiate the steps of biofilm formation. At low bacterial concentrations, the biofilm produces minimal inflammation. However, once bacterial concentration surpasses a critical density, the bacteria proliferate unchecked by the immune system, eliciting chronic inflammation, scarring, and fibrosis surrounding the implant. Therefore, intra-operative strategies to prevent contamination of the implant with breast and skin flora have been adopted as common practice. These include antibiotic irrigation of the breast pocket, as well atraumatic pocket dissection, antibiotic soaking of implants prior of placements, glove changing before implant handling, implant insertion with a funnel, and use of nipple barriers.

History of breast pocket irrigation

Intra-operative breast pocket irrigation has been investigated as a practice to reduce incidence of implant-associated infections and capsular contracture for over three decades. In their prospective analysis of various local antibacterial methods in patients undergoing augmentation mammaplasty, Burkhardt et al . were the first to report a reduction in the early postoperative onset and final incidence of capsular contracture when compared with saline irrigation control. Throughout the 1990s, povidone-iodine irrigation was the antibiotic solution of choice due to its cost-effectiveness, low allergy risk, and bactericidal effects against a broad spectrum of organisms. However, in 1997, Mentor Corporation found an association of valve-patch delamination of saline implant in vitro analyses of long-term intraluminal povidone-iodine solution fills. This was further corroborated when a second study evaluated the effect of povidone-iodine on silicone elastomer tubing, which demonstrated deleterious changes in elastomer strength sufficient to result in rupture of the tubes on explantation. In the spring of 2000, the US Food and Drug Administration (FDA) reacted to these reports by issuing a ban on the use of any povidone-iodine with breast implants. Many groups were disinclined to adopt these rigorous FDA regulations due to lack of evidence regarding the dangers of povidone-iodine irrigation. Zambacos et al . published an in vitro experiment that showed povidone-iodine to have no significantly different effect on the tensile strength of silicone elastomer shells after 4 weeks of incubation when compared with saline. Other physicians continued to use povidone-iodine irrigation despite the FDA ban, stating the benefits to decreasing incidence of capsular contracture greatly outweigh the minimal-to-no risk of implant rupture. Despite the physician opposition and host of contrary evidence to the risk povidone-iodine pocket irrigation, it was not until 2017 that the FDA instituted a change in the “directions for use” that removed the ban against povidone-iodine use in breast augmentation. During the 17-year ban, surgeons were tasked with developing novel antibiotic solutions for breast pocket irrigation. Notably, Adams et al . recommended a povidone-iodine-free triple-antibiotic solution consisting of a combination of bacitracin, cefazolin, and gentamicin, though they concluded that this solution was less effective at attacking bacterial cell membranes than its povidone-iodine-containing counterpart. Since its creation, triple-antibiotic solution (TAS) has gained popularity. According to a 2018 national survey of ASPS members, most surgeon respondents prefer TAS and TAS with Betadine, with only a small minority (11%) reporting the use of strictly Betadine variants. More recently, amber glass-stabilized hypochlorous acid and chlorhexidine gluconate have been used for breast pocket irrigation.

Antibacterial solutions