Establishment and Characterization of Bacterial Infection of Breast Implants in a Murine Model.

BACKGROUND: Staphylococcus epidermidis and Pseudomonas aeruginosa are the most common causes of Gram-positive and Gram-negative breast implant-associated infection. Little is known about how these bacteria infect breast implants as a function of implant surface characteristics and timing of infection. OBJECTIVES: The aim of this work was to establish a mouse model for studying the impact of various conditions on breast implant infection. METHODS: Ninety-one mice were implanted with 273 breast implant shells and infected with S. epidermidis or P. aeruginosa. Smooth, microtextured, and macrotextured breast implant shells were implanted in each mouse. Bacterial inoculation occurred during implantation or 1 day later. Implants were retrieved 1 or 7 days later. Explanted breast implant shells were sonicated, cultured, and colony-forming units determined or analyzed with scanning electron microscopy. RESULTS: P. aeruginosa could be detected on all device surfaces at 1- and 7- days post infection (dpi), when mice were implanted and infected concurrently or when they were infected 1- day after implantation. However, P. aeruginosa infection was more robust on implant shells retrieved at 7 dpi and particularly on the macrotextured devices that were infected 1 day post implantation. S. epidermidis was mostly cleared from implants when mice were infected and implanted concurrently. Other the other hand, S. epidermidis could be detected on all device surfaces at 1 dpi and 2 days post implantation. However, S. epidermdis infection was suppressed by 7 dpi and 8 days post implantation. CONCLUSIONS: S. epidermidis required higher inoculating doses to cause infection and was cleared within 7 days. P. aeruginosa infected at lower inoculating doses, with robust biofilms noted 7 days later.

Deposition of Host Matrix Proteins on Breast Implant Surfaces Facilitates Staphylococcus Epidermidis Biofilm Formation: In Vitro Analysis.

BACKGROUND: Staphylococcus epidermidis is a primary cause of breast implant-associated infection. S epidermidis possesses several virulence factors that enable it to bind both abiotic surfaces and host factors to form a biofilm. In addition S epidermidis colocalizes with matrix proteins coating explanted human breast implants. OBJECTIVES: The authors sought to identify matrix proteins that S epidermidis may exploit to infect various breast implant surfaces in vitro. METHODS: A combination of in vitro assays was used to characterize S epidermidis strains isolated from human breast implants to gain a better understanding of how these bacteria colonize breast implant surfaces. These included determining the (1) minimum inhibitory and bactericidal concentrations for irrigation solutions commonly used to prevent breast implant contamination; (2) expression and carriage of polysaccharide intercellular adhesin and serine-aspartate repeat proteins, which bind fibrinogen (SdrG) and collagen (SdrF), respectively; and (3) biofilm formation on varying implant surface characteristics, in different growth media, and supplemented with fibrinogen and Types I and III collagen. Scanning electron microscopy and immunofluorescence staining analyses were performed to corroborate findings from these assays. RESULTS: Textured breast implant surfaces support greater bacterial biofilm formation at baseline, and the addition of collagen significantly increases biomass on all surfaces tested. We found that S epidermidis isolated from breast implants all encoded SdrF. Consistent with this finding, these strains had a clear affinity for Type I collagen, forming dense, highly structured biofilms in its presence. CONCLUSIONS: The authors found that S epidermidis may utilize SdrF to interact with Type I collagen to form biofilm on breast implant surfaces.

Insights into the Microbiome of Breast Implants and Periprosthetic Tissue in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Though rare, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a CD30+ T-cell lymphoma associated with textured breast implants, has adversely impacted our perception of the safety of breast implants. Its etiology unknown, one hypothesis suggests an initiating inflammatory stimulus, possibly infectious, triggers BIA-ALCL. We analyzed microbiota of breast, skin, implant and capsule in BIA-ALCL patients (n = 7), and controls via culturing methods, 16S rRNA microbiome sequencing, and immunohistochemistry. Alpha and beta diversity metrics and relative abundance of Gram-negative bacteria were calculated, and phylogenetic trees constructed. Staphylococcus spp., the most commonly cultured microbes, were identified in both the BIA-ALCL and contralateral control breast. The diversity of bacterial microbiota did not differ significantly between BIA-ALCL and controls for any material analyzed. Further, there were no significant differences in the relative abundance of Gram-negative bacteria between BIA-ALCL and control specimens. Heat maps suggested substantial diversity in the composition of the bacterial microbiota of the skin, breast, implant and capsule between patients with no clear trend to distinguish BIA-ALCL from controls. While we identified no consistent differences between patients with BIA-ALCL-affected and contralateral control breasts, this study provides insights into the composition of the breast microbiota in this population.

The Detection of Bacteria and Matrix Proteins on Clinically Benign and Pathologic Implants.

BACKGROUND: Bacterial contamination of breast implants causes infection, can lead to capsular contracture, and is implicated in breast implant-associated anaplastic large cell lymphoma. Bacteria, however, also colonize clinically benign breast implants and little is known about the biologic signals that trigger the switch from a benign to pathologic state. METHODS: Explanted smooth as well as Biocell and Siltex textured breast implants associated with clinically normal and pathologic conditions were analyzed in this observational study. Immunofluorescence and bacterial culture techniques were performed. To avoid sampling bias, implant surfaces >25 sq cm were analyzed. RESULTS: Bacteria were detected on 9 of 22 clinically normal explanted devices or periprosthetic capsules, including 40% of Biocell tissue expanders and 75% of Biocell textured implants. Staphylococcus epidermidis was identified in 67% of the bacteria-positive capsular contractures. Fibrinogen was present on 17 of 18, and collagen on 13 of 18 analyzed breast implants. S. epidermidis co-localized with collagen, while group B streptococci and Klebsiella pneumoniae co-localized with fibrinogen. CONCLUSIONS: Bacteria are often detectable on clinically benign breast implants when a multimodal approach is applied to a substantial proportion of the device surface to avoid sampling bias. The impact of bacteria on breast implant pathology should be studied in the presence of an adequate negative control group to account for clinically benign bacteria. Disruption of the interaction of bacteria with matrix proteins coating the surface of breast implants may represent a nonantibiotic strategy for the prevention of breast implant bacterial contamination.

Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract.

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of catheter-associated urinary tract infection (CAUTI), which frequently progresses to more serious invasive infections. We adapted a mouse model of CAUTI to investigate how catheterization increases an individual's susceptibility to MRSA UTI. This analysis revealed that catheterization was required for MRSA to achieve high-level, persistent infection in the bladder. As shown previously, catheter placement induced an inflammatory response resulting in the release of the host protein fibrinogen (Fg), which coated the bladder and implant. Following infection, we showed that MRSA attached to the urothelium and implant in patterns that colocalized with deposited Fg. Furthermore, MRSA exacerbated the host inflammatory response to stimulate the additional release and accumulation of Fg in the urinary tract, which facilitated MRSA colonization. Consistent with this model, analysis of catheters from patients with S. aureus-positive cultures revealed colocalization of Fg, which was deposited on the catheter, with S. aureus Clumping Factors A and B (ClfA and ClfB) have been shown to contribute to MRSA-Fg interactions in other models of disease. We found that mutants in clfA had significantly greater Fg-binding defects than mutants in clfB in several in vitro assays. Paradoxically, only the ClfB- strain was significantly attenuated in the CAUTI model. Together, these data suggest that catheterization alters the urinary tract environment to promote MRSA CAUTI pathogenesis by inducing the release of Fg, which the pathogen enhances to persist in the urinary tract despite the host's robust immune response.