“…Vancomycin concentrations well over 4000 lg/mL are readily obtained in the knee immediately after infusion, and with a daily infusion regimen, this level can be achieved daily for 6 weeks or longer [46]. Moderate concentrations of antibiotics are necessary to prevent biofilm formation [11,12], but once biofilm and persister cells have formed, concentrations of orders of magnitude greater (as high as 4000 lg/ mL) are necessary to eradicate the bacteria within the biofilm [7,8,11,12,17,27,31,45,49,50]. Clearly, some risk of toxicity exists with direct intraarticular infusion of antibiotics, but this method may be the safest way to achieve high antibiotic levels over time [54][55][56] while allowing for the opportunity to decrease the dose, change antibiotics, or stop them altogether in the case of allergic reactions or renal toxicity.…”