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Medical implant infections
S. aureus is often found in biofilms formed on medical devices implanted in the body or on human tissue. S. aureus biofilm is the predominant cause of orthopedic implant-related infections but is also found on cardiac implants, vascular grafts, various catheters, and cosmetic surgical implants. After implantation, the surface of these devices becomes coated with host proteins, which provide a rich surface for bacterial attachment and biofilm formation. Once the device becomes infected, it must by completely removed since S. aureus biofilm cannot be destroyed by antibiotic treatments.

Current therapy for S. aureus biofilm-mediated infections involves surgical removal of the infected device followed by antibiotic treatment. Conventional antibiotic treatment alone is not effective in eradicating such infections. An alternative to post-surgical antibiotic treatment is using antibiotic-loaded, dissolvable calcium sulfate beads, which are implanted with the medical device. These beads can release high doses of antibiotics at the desired site to prevent the initial infection. The most commonly used antibiotic for calcium sulfate beads is gentamicin in mainland Europe, and tobramycin in the U.S. and UK.

Novel treatments for S. aureus biofilm involving nano silver particles, bacteriophages, and plant-derived antibiotic agents, are being studied. These agents have shown inhibitory effects against S. aureus embedded in biofilms. A class of enzymes have been found to have biofilm matrix degrading ability and thus may be used as biofilm dispersal agents in combination with antibiotics.

Biofilm
S. aureus biofilm has high resistance to antibiotic treatments and host immune response. One hypothesis for explaining this is that the biofilm matrix protects the embedded cells by acting as a barrier to prevent antibiotic penetration. However, recent findings have shown that the biofilm matrix is composed with many water channels, so this hypothesis is becoming increasingly less likely. But it is possible that biofilm matrix contains antibiotic‐degrading enzymes such as β-lactamases, which can prevent antibiotic penetration. Another hypothesis is that the conditions in the biofilm matrix favor the formation of persister cells, which are highly antibiotic resistant, dormant bacterial cells. S. aureus biofilms also have high resistance to host immune response. Even though the exact mechanism of resistance is unknown, studies have demonstrated that S. aureus biofilms had increased growth under the presence of cytokines produced by the host immune response. Host antibodies are less effective for S. aureus biofilm due to the heterogenous antigen distribution, where an antigen may be present in some areas of the biofilm but completely absent from other areas.