Abstract
Introduction
PJI is a devastating complication following total joint arthroplasty. In this study, we explore the efficacy of a bacteriophage-derived lysin, PlySs2, against in-vitro biofilm on titanium implant surfaces and in an acute in-vivo murine debridement antibiotic implant retention (DAIR) model of PJI.
Methods
In-vitro: Xen 36 S. aureus biofilm was grown on Ti-6Al-4V mouse tibial implants for 1 day or 5 days and subsequently exposed to growth media, 1000× minimal inhibitory concentration (MIC) Vancomycin, or 5× MIC PlySs2. Implants were sonicated and analyzed for Colony Forming Units (CFU).
In-vivo: A Ti-6Al-4V implant was inserted into the proximal tibia of C57BL/6J mice (n=21). All mice received 104 CFU inoculation of Xen 36 S. aureus to the knee joint capsule and the infection was permitted 5 days to progress. On day 5 the mice were separated into three groups (n=7/group): (1) no further surgical intervention (control group), (2) irrigation and debridement (I&D) with saline, (3) I&D with 2mg/mL PlySs2. No implant-exchange was performed to mimic a debridement, antibiotic, and implant retention (DAIR) therapeutic strategy. All mice were sacrificed at day 10.
Results
CFU counts for 1-day and 5-day in-vitro grown biofilm on implants demonstrate a >3log-fold reduction with PlySs2 compared to Vancomycin (p=0.01) with no significant difference between Vancomycin and control. In-vivo the addition of PlySs2 to Vancomycin treated mice reduces bacterial load in the periposthetic tissue and implant (p<0.05) with 5 days of treatment.
Conclusion
PlySs2 5× MIC exhibits superior anti-microbial effect compared to Vancomycin on implants with 1-day and 5–5day biofilm maturities. The addition of PlySs2 to Vancomycin treatment of an acute established PJI further reduces tissue CFU and implants CFU.
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