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=13

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=<p><bold>Background:</bold> Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated <italic>Staphylococcus aureus</italic>. In a recent experimental study, savirin has been used to prevent and treat <italic>S. aureus</italic> 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.</p><p><bold>Materials and methods:</bold> The <italic>in-vitro</italic> antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against <italic>S. aureus</italic> 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 (<italic>icaA, icaD</italic>, <italic>eno</italic>, <italic>fib</italic>, <italic>ebps</italic>, and <italic>agr</italic>) in <italic>S. aureus</italic> was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The <italic>in-vivo</italic> efficacy of savirin alone and with cefazolin to prevent <italic>S. aureus</italic> 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.</p><p><bold>Results:</bold> Savirin inhibited planktonic and biofilm <italic>in-vitro</italic> growth of <italic>S. aureus,</italic> showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key <italic>S. aureus</italic> biofilm-related genes (<italic>icaA, icaD</italic>, <italic>eno</italic>, <italic>fib</italic>, <italic>ebps</italic>, and <italic>agr</italic>). 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.</p><p><bold>Conclusion:</bold> Savirin adjuvant therapy may prevent biofilm formation and <italic>S. aureus</italic> PJI. This study gives baseline data for using savirin for the prevention as well as treatment of <italic>S. aureus</italic> PJI in future animal studies.</p>