Poly(trimethylene carbonate) as a carrier for rifampicin and vancomycin to target therapy-recalcitrant staphylococcal biofilms

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Standard antibiotic therapy in osteomyelitis patients is of limited value when methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), or small-colony variants (SCV) are present. Far better results are obtained by local drug delivery of antibiotic combinations including rifampicin, using a suitable carrier. We therefore investigated release kinetics of antibiotics from biodegradable poly(trimethylene carbonate) (PTMC) and in vitro biofilm inhibition of MRSA, MRSE, and S. aureus SCV strains in the course of 24, 72, and 168 h treatment by PTMC, either unloaded, gentamicin-loaded, loaded with rifampicin and fosfomycin, or rifampicin and vancomycin. PTMC appeared to be a suitable carrier for rifampicin alone or in combination with other antibiotics. Biofilm colony forming units and metabolic activity measurement (MTT assay) demonstrated significant (p < 0.05) inhibition for all strains when PTMC loaded with rifampicin and vancomycin was employed, especially after 168 h treatment. Confocal laser scanning microscopy images showed similar qualitative results. PTMC loaded with only gentamicin did not show any inhibition. This exemplifies that PTMC loaded with rifampicin and vancomycin holds promise for the treatment of recalcitrant osteomyelitis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

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