Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections

Diagnosis and Management of Infected Total Knee Arthroplasty§

Infection following total knee arthroplasty can be difficult to diagnose and treat. Diagnosis is multifactorial and relies on the clinical picture, radiographs, bone scans, serologic tests, synovial fluid examination, intra-operative culture and histology. Newer techniques including ultrasonication and molecular diagnostic studies are playing an expanded role. Two-stage exchange arthroplasty with antibiotic cement and 4-6 weeks of intravenous antibiotic treatment remains the most successful intervention for infection eradication. There is no consensus on the optimum type of interval antibiotic cement spacer. There is a limited role for irrigation and debridement, direct one-stage exchange, chronic antibiotic suppression and salvage procedures like arthrodesis and amputation. We examine the literature on each of the diagnostic modalities and treatment options in brief and explain their current significance