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

Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated . In a recent experimental study, savirin has been used to prevent and treat 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. The antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against 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 (, , , , and ) in was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The efficacy of savirin alone and with cefazolin to prevent 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. Savirin inhibited planktonic and biofilm growth of showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key biofilm-related genes (, , , , and ). 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. Savirin adjuvant therapy may prevent biofilm formation and PJI. This study gives baseline data for using savirin for the prevention as well as treatment of PJI in future animal studies.