Biomaterials 24 (2003) 1829–1831 Technical note Residual gentamicin-release from antibiotic-loaded polymethylmethacrylate beads after 5 years of implantation Dani . elle Neut a,b , Hilbrand van de Belt c , Jim R. van Horn a , Henny C. van der Mei b , Henk J. Busscher b, * a Department of Orthopedic Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands b Department of Biomedical Engineering, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands c Department of Orthopedic Surgery, Streekziekenhuis Coevorden—Hardenberg, J. Weitkamplaan 4 a , 7772 SE Hardenberg, The Netherlands Received 30 July 2002; accepted 11 December 2002 Abstract In infected joint arthroplasty, high local levels of antibiotics are achieved through temporary implantation of non-biodegradable gentamicin-loaded polymethylmethacrylate beads. Despite their antibiotic release, these beads act as a biomaterial surface to which bacteria preferentially adhere, grow and potentially develop antibiotic resistance. In routine clinical practice, these beads are removed after 14 days, but for a variety of reasons, we were confronted with a patient in which these beads were left in situ for 5 years. Retrieval of gentamicin-loaded beads from this patient constituted an exceptional case to study the effects of long-term implantation on potentially colonizing microflora and gentamicin release. Gentamicin-release test revealed residual antibiotic release after being 5 years in situ and extensive microbiological sampling resulted in recovery of a gentamicin-resistant staphylococcal strain from the bead surface. This case emphasizes the importance of developing biodegradable antibiotic-loaded beads as an antibiotic delivery system. r 2003 Elsevier Science Ltd. All rights reserved. Keywords: Polymethylmethacryate; Beads; Gentamicin; Biodegradable; Antibiotic resistance 1. Introduction Gentamicin-loaded polymethylmethacrylate (PMMA) beads constitute an effective drug delivery system for local antibiotic therapy in bone and soft-tissue infec- tions, as they enable gentamicin concentrations at the site of the infection to become much higher than can be achieved with systemic application. The release of gentamicin from the beads is a diffusion process as in all antibiotic-loaded bone cements [1]. Gentamicin- loaded PMMA beads, however, release much more gentamicin than solid bone cement plugs, mainly due to the greatly increased surface area of the many, relatively small beads (see Fig. 1). Patients are treated with gentamicin-loaded beads during approximately 14 days, after which 20–70% of the total amount of gentamicin incorporated in the beads is released into the body and gentamicin concen- trations drop greatly [2]. The main effect of gentamicin is therefore immediately after implantation of the beads and long-term implantation of the beads is of no value in combating infection. In clinical practice, the gentamicin- loaded beads are usually removed after 14 days, although permanent implantation is not absolutely contra-indicated. Removal must be weighed against the risk of leaving the beads in the human body. The gentamicin-loaded beads can act as a biomaterial surface to which bacteria preferentially adhere and grow. If a relapse occurs, the beads will form a biomaterial center of infection [3]. Likely, the slow release of gentamicin from the cement matrix into the local environment is an efficient way to induce and/or select for resistant small colony variants [4], as the onset to the development of overall antibiotic resistance of a strain. Recently, we were confronted with a patient in whom these beads were left in situ for 5 years. Retrieval of gentamicin-loaded beads from this patient constituted an exceptional case to study the effects of long-term implantation on potentially colonizing microflora and gentamicin release. *Corresponding author. Tel.: +31-50-3633140; fax: +31-50- 3633159. E-mail address: h.j.busscher@med.rug.nl (H.J. Busscher). 0142-9612/03/$-see front matter r 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0142-9612(02)00614-2