AUTHOR=Pant Narayan , Miranda-Hernandez Socorro , Rush Catherine , Warner Jeffrey , Eisen Damon P. 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.989417

DOI=10.3389/fphar.2022.989417

ISSN=1663-9812

ABSTRACT=Background: 
Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated Staphylococcus aureus. In a recent experimental study, savirin has been used to prevent and treat S. aureus 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.
Materials and methods: 
The effect of savirin treatment on the expression of the key biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr) in S. aureus was studied using qRTPCR. The in-vivo efficacy of savirin alone and with cefazolin to prevent S. aureus 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.
Results: 
Savirin inhibited planktonic and biofilm in-vitro growth of S. aureus, showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key S. aureus biofilm-related genes. Savirin significantly reduced bacterial counts in joint implants in comparison with PBS treated control, while savirin plus cefazolin reduced bacterial counts on both implants and peri-prosthetic tissues. 
Conclusion:
Savirin adjuvant therapy may prevent biofilm formation and S. aureus PJI. This study lays a foundation for using savirin for prevention as well as treatment of S. aureus PJI in future animal studies.