title: Rifampicin-fosfomycin coating for cementless endoprostheses: antimicrobial effects against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA).
abstract: New strategies to decrease infection rates in cementless arthroplasty are needed, especially in the context of the growing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections. The purpose of this study was to investigate the antimicrobial activity of a rifampicin-fosfomycin coating against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA in a rabbit infection prophylaxis model. Uncoated or rifampicin-fosfomycin-coated K-wires were inserted into the intramedullary canal of the tibia in rabbits and contaminated with an inoculation dose of 10(5) or 10(6) colony-forming units of MSSA EDCC 5055 in study 1 and MRSA T6625930 in study 2, respectively. After 28days the animals were killed and clinical, histological and microbiological assessment, including pulse-field gel electrophoresis, was conducted. Positive culture growth in agar plate testing and/or clinical signs and/or histological signs were defined positive for infection. Statistical evaluation was performed using Fisher's exact test. Both studies showed a statistically significant reduction of infection rates for rifampicin-fosfomycin-coated implants compared to uncoated K-wires (P=0.015). In both studies none of the 12 animals that were treated with a rifampicin-fosfomycin-coated implant showed clinical signs of infection or a positive agar plate testing result. In both studies, one animal of the coating group showed the presence of sporadic bacteria with concomitant inflammatory signs in histology. The control groups in both studies exhibited an infection rate of 100% with clear clinical signs of infection and positive culture growth in all animals. In summary, the rifampicin-fosfomycin-coating showed excellent antimicrobial activity against both MSSA and MRSA, and therefore warrants further clinical testing.
authors.affiliation: Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, 35385 Giessen, Germany; Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany. Electronic address: volker.alt@chiru.med.uni-giessen.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Alt
authors.affiliation: Biomet Deutschland GmbH, 14167 Berlin, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Kirchhof
authors.affiliation: Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, 35385 Giessen, Germany; Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Seim
authors.affiliation: Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, 35385 Giessen, Germany; Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hrubesch
authors.affiliation: Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany.
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Lips
authors.affiliation: Biomet Deutschland GmbH, 14167 Berlin, Germany.
authors.forename: Henrich
authors.initials: H
authors.lastname: Mannel
authors.affiliation: Institute of Medical Microbiology, University Hospital of Giessen-Marburg, Campus Giessen, 35392 Giessen, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Domann
authors.affiliation: Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, 35385 Giessen, Germany; Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schnettler
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000737:chemistry / Q000494:pharmacology; D001864:Bone Wires; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D005578:Fosfomycin / Q000737:chemistry / Q000494:pharmacology; D008422:Materials Testing; D055624:Methicillin-Resistant Staphylococcus aureus / Q000254:growth & development*; D019736:Prostheses and Implants; D011817:Rabbits; D012293:Rifampin / Q000737:chemistry / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000517:prevention & control*
chemical_list: D000904:Antibiotics, Antitubercular; D020099:Coated Materials, Biocompatible; D005578:Fosfomycin; D012293:Rifampin
keywords: Infection; MRSA; Prosthesis; Staphylococcus aureus