Rifampicin–fosfomycin coating for cementless endoprostheses: Antimicrobial effects against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) Volker Alt a,b,⇑ , Kristin Kirchhof c , Florian Seim a,b , Isabelle Hrubesch a,b , Katrin S. Lips b , Henrich Mannel c , Eugen Domann d , Reinhard Schnettler a,b a Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, 35385 Giessen, Germany b Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany c Biomet Deutschland GmbH, 14167 Berlin, Germany d Institute of Medical Microbiology, University Hospital of Giessen-Marburg, Campus Giessen, 35392 Giessen, Germany article info Article history: Received 17 February 2014 Received in revised form 7 May 2014 Accepted 9 June 2014 Available online xxxx Keywords: Infection Prosthesis 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 meth- icillin-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 28 days 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 bac- teria 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. Ó 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Infections in total arthroplasty such as total knee and total hip arthroplasty are devastating situations with a negative impact both on the quality of life for the patient and on the cost to the health- care system [1]. Frequently, surgical treatment to exchange the infected prosthesis is the only option for treatment of the infection. However, failure rates with reinfection or persistence of the infec- tion of this extensive surgical treatment of 20% have been reported [2]. The virulence of methicillin-resistant Staphylococcus aureus (MRSA) has turned this pathogen not only into the most deadly bacteria in North America [3] but also into a complex problem in the context of total joint infections. Previous reports have shown that the treatment outcome for patients with infections with mul- tiresistant bacteria such as MRSA is significantly worse compared to infections with non-multiresistant bacteria with higher recur- rence of infection of up to 61%, resulting in resection arthroplasty or even amputation [4,5]. Therefore, all efforts should be under- taken to optimize infection prophylaxis in total joint arthroplasty, including prophylaxis against MRSA. The principle of local delivery of antibiotics by antibiotic- loaded bone cement was introduced by Buchholz and Engelbrecht [6] and was intended to optimize infection prophylaxis by high concentrations of the antibiotic in direct vicinity to the implant http://dx.doi.org/10.1016/j.actbio.2014.06.013 1742-7061/Ó 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: Department of Trauma Surgery Giessen, University Hospital of Giessen-Marburg, Campus Giessen, 35385 Giessen, Germany. E-mail address: volker.alt@chiru.med.uni-giessen.de (V. Alt). Acta Biomaterialia xxx (2014) xxx–xxx Contents lists available at ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat Please cite this article in press as: Alt V et al. Rifampicin–fosfomycin coating for cementless endoprostheses: Antimicrobial effects against methicillin- sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Acta Biomater (2014), http://dx.doi.org/10.1016/ j.actbio.2014.06.013