title: Titanium-tethered vancomycin prevents resistance to rifampicin in Staphylococcus aureus in vitro.
abstract: Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone). Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.
authors.affiliation: Laboratory for Musculoskeletal Research and Innovation, Department of Orthopaedics, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Rottman
authors.forename: Joel
authors.initials: J
authors.lastname: Goldberg
authors.forename: S Adam
authors.initials: SA
authors.lastname: Hacking
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D012293:Rifampin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; D014640:Vancomycin; D014025:Titanium; D012293:Rifampin