Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection

Abstract

<b>Background:</b> Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated <i>Staphylococcus aureus</i>. In a recent experimental study, savirin has been used to prevent and treat <i>S. aureus</i> skin infections in animal models. We explored the application of savirin in a PJI mouse model to determine its utility as an adjunct therapy to prevent PJI. <b>Materials and methods:</b> The <i>in-vitro</i> antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against <i>S. aureus</i> were investigated using broth microdilution and crystal violet staining method, respectively. The effect of savirin treatment on the expression of the key biofilm-related genes (<i>icaA, icaD</i>, <i>eno</i>, <i>fib</i>, <i>ebps</i>, and <i>agr</i>) in <i>S. aureus</i> was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The <i>in-vivo</i> efficacy of savirin alone and with cefazolin to prevent <i>S. aureus</i> PJI was determined using a clinically relevant PJI mouse model. Mice were randomized into five groups (n = 8/group): 1) infected K-wire savirin treated group, 2) infected K-wire cefazolin treated group, 3) infected K-wire savirin plus cefazolin treated group, 4) infected K-wire PBS treated group, 5) sterile K-wire group. Savirin was administered subcutaneously immediately post-surgery and intravenous cefazolin was given on day seven. <b>Results:</b> Savirin inhibited planktonic and biofilm <i>in-vitro</i> growth of <i>S. aureus,</i> showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key <i>S. aureus</i> biofilm-related genes (<i>icaA, icaD</i>, <i>eno</i>, <i>fib</i>, <i>ebps</i>, and <i>agr</i>). Savirin significantly reduced bacterial counts on joint implants in comparison with the PBS treated control, while savirin plus cefazolin reduced bacterial counts on both implants and peri-prosthetic tissues. <b>Conclusion:</b> Savirin adjuvant therapy may prevent biofilm formation and <i>S. aureus</i> PJI. This study gives baseline data for using savirin for the prevention as well as treatment of <i>S. aureus</i> PJI in future animal studies.