Joint replacement surgery enhances patient's quality of life by relieving pain and restoring function. However, a significant number of prosthetic joints fail due to biofilm related Staphylococcus aureus infection. Currently available prosthetic joint infection (PJI) treatments are traumatic, expensive, and have significant failure rates. Non-antimicrobial adjuvant therapy that can treat PJI would be beneficial. Savirin, a small synthetic molecule, has previously been shown to be effective in prevention and treatment of S. aureus skin and subcutaneous infections in animal models.
We studied the efficacy of savirin ± cephazolin to treat S. aureus PJI, using in-vitro techniques and a clinically relevant mouse model, whereby biofilm was established on an infected knee implant. S. aureus was inoculated onto the implant's cut end and remained protruding into the joint space. Mice were randomised into five groups (n=8/group): (i) sterile implants; (ii) infected implants + PBS; (iii) infected implants + cephazolin; (iv) infected implants + savirin and; (v) infected implants + savirin and cephazolin. Savirin (40µg) was administered subcutaneously immediately post-surgery, while cephazolin (2.5µg/g) was injected intravenously on day seven post-surgery. On day 14 post-surgery, mice were euthanised and implants and peri-prosthetic joint tissues were removed for S. aureus culture and histological study.
Savirin ± cephazolin showed in-vitro antimicrobial and antibiofilm activities against S. aureus and down regulated the expression of some key biofilm related genes (icaA, icaD, eno, fib, ebps and agr) in S. aureus. In animal experiments, savirin significantly reduced bacterial counts on implants in comparison to the PBS treated control (log10cfu/ml, 3.2 versus 1.6) (p<0.05). In addition, savirin + cephazolin reduced bacterial counts on both implants (log10cfu/ml, 3.2 versus 1) and peri-prosthetic tissues (log10cfu/ml, 7.1 versus 4.5) in comparison to PBS treated control (p<0.05). These findings were supported by tissue histology. Our results suggest that savirin may be a good candidate for further development as an adjuvant therapy for PJI treatment.