Our current challenge in the management of prosthetic joint infection is the eradication of biofilms which has driven the need for improved antimicrobial agents and regimens. In this study, the antimicrobial peptide, LL-37, and silver nanoparticles (AgNPs) were investigated for their antimicrobial efficacies against Staphylococcus aureus ( S . aureus ), a microorganism commonly implicated in biofilm-related infections. These antimicrobials were compared to conventional antibiotics and combination treatments with rifampin. Using a Centers for Disease Control reactor, 24 h S . aureus biofilms were formed on cobalt-chromium discs and the anti-biofilm activity was determined by quantifying the amount of colony forming units following treatments. We found that LL-37 was the most efficacious antimicrobial agent with a more than 4 log reduction in colony counts. In comparison, silver nanoparticles and conventional antibiotics were not as efficacious, with a less than 1 log reduction in colony counts. Antimicrobial combination treatments with rifampin significantly increased the log reduction for AgNPs and gentamicin, although still significantly less than LL-37 in isolation. Furthermore, kinetic studies revealed the rapid elimination of S . aureus biofilm with LL-37. Collectively, the results of this study demonstrated that LL-37 was an effective agent against S . aureus biofilms and may have potential clinical applications in the eradication of biofilms and treatment of prosthetic joint infection.

Background: Posterior hip precautions have been routinely prescribed to decrease dislocation rates. The purpose of this study was to determine if the absence of hip precautions improved early recovery after total hip arthroplasty via the posterolateral approach. METHODS:Patients undergoing total hip arthroplasty via the posterolateral approach at three centers were enrolled. Patients meeting the selection criteria were randomized to Standard Hip Precautions (SHP) or No Hip Precautions (NHP) for six weeks following surgery. HOOS Jr., health state visual analog score, and rate of pain scores were recorded preoperatively and in subsequent postoperative visits; dislocation episodes were also noted. Standard statistical analysis was performed. RESULTS:From 2016-2017, 159 patients were randomized to SHP and 154 patients were randomized to NHP. Controlling for the center at which the surgery was performed, the only difference in outcome scores between the two groups was at two weeks; the NHP group had a lower HOOS Jr. score when compared to the SHP group (p=0.03). There was no difference in outcome scores at any other time points when compared to preoperative assessments. In the SHP group, there were two recorded dislocations (1.3%) and one in the NHP group 0.7% (p=0.62). CONCLUSION:In this multicenter, randomized, controlled study, the absence of hip precautions in the postoperative period did not improve subjective outcomes which may be explained by the

Bone and joint infections caused by Staphylococcus aureus are becoming increasingly difficult to treat due to rising antibiotic resistance, resilient biofilms and intracellular survival of S. aureus. It has been challenging to identify and develop antimicrobial agents that can be used to kill extracellular and intracellular bacteria while having limited toxicity towards host cells. In addressing this challenge, this study investigates the antimicrobial efficacy and toxicity of silver nanoparticles (AgNPs).Methods: Intracellular bacteria were generated using a co-culture model of human osteoblast cells and S. aureus. Extracellular and intracellular S. aureus were treated with AgNPs, antibiotics and their combinations, and numbers of colonies were quantified. Toxicity of AgNPs against human osteoblast cells was determined by quantifying the number of viable cells after treatment.Results: AgNPs demonstrated excellent antimicrobial activity against extracellular S. aureus with a 100% killing efficacy at concentrations as low as 56 lM, along with a high intracellular killing efficacy of 76% at 371 lM. AgNPs were non-toxic or slightly toxic towards human osteoblasts at the concentrations studied (up to 927 lM). Moreover, smaller-sized (40 nm) AgNPs were more efficacious in killing bacteria compared with their larger-sized (100 nm) counterparts and synergistic antimicrobial effects against extracellular bacteria were observed when AgNPs were combined with gentamicin.Conclusions: AgNPs and their combination with antibiotics have demonstrated high extracellular and intracellular bacterial killing and presented unique aspects for potential clinical applications, especially for chronic and recurrent infections where intracellular bacteria may be the cause.

Chronic and recurrent bone infections occur frequently but have not been explained. Staphylococcus aureus (S. aureus) is often found among chronic and recurrent infections and may be responsible for such infections. One possible reason is that S. aureus can internalize and survive within host cells and by doing so, S. aureus can evade both host defense mechanisms and most conventional antibiotic treatments. In this study, we hypothesized that intra-cellular S. aureus could induce infections in vivo. Osteoblasts were infected with S. aureus and, after eliminating extra-cellular S. aureus, inoculated into an open fracture rat model. Bacterial cultures and radiographic observations at post-operative day 21 confirmed local bone infections in animals inoculated with intra-cellular S. aureus within osteoblasts alone. We present direct in vivo evidence that intra-cellular S. aureus could be sufficient to induce bone infection in animals; we found that intra-cellular S. aureus inoculation of as low as 10 2 colony forming units could induce severe bone infections. Our data may suggest that intra-cellular S. aureus can "hide" in host cells during symptom-free periods and, under certain conditions, they may escape and lead to infection recurrence. Intra-cellular S. aureus therefore could play an important role in the pathogenesis of S. aureus infections, especially those chronic and recurrent infections in which disease episodes may be separated by weeks, months, or even years.

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