In vivo application of biodegradable controlled antibiotic release systemsfor the treatment of implant-related osteomyelitis

In this study the construction and in vivo testing of antibiotic-loaded pol yhydroxyalkanoate rods were planned for use in the treatment of implant-rel ated osteomyelitis. The rods were constructed of poly(3-hydroxybutyrare-co- 3-hydroxyvalerate) and poly(3hydroxybutyrate-co-4-hydroxybutyrate), carryin g 50% (w/w) Sulperazone(R) or Duocid(R). They were implanted in rabbit tibi a in which implant-related osteomyelitis (IRO) had been induced with Staphy lococcus aureus. The effectiveness of the antibiotics in the treatment of I RO was determined. The establishment of IRO with bacterial inoculation was complete after 3 weeks with 100% infection rate in all groups. There was no contamination or super-infection. Both antibiotics were found to be highly effective against the bacteria. Following the application of Sulperazone-P (3-HB-co-4-HB) rods, no infective agents could be isolated from the infecti on site within the 6-week test period, indicating complete treatment of the infection. Macroscopical evaluation at follow-up revealed no drainage, min imal swelling and increase in local warmth, most probably due to the surger y rather than to a reaction towards the implant. The overall scores for rad iological findings by the end of 6 weeks were 0.8/5 for the antibiotic-load ed rod implanted in the right limb, and 1.1/5 For the antibiotic-free rod i mplanted in the left limb. There was no statistical difference between the antibiotic-loaded and antibiotic-free polymeric rods. In vivo drug release was almost complete within the first week. One interesting observation, how ever, was that the therapy was still very effective even when the release r ate was very high. In the SEM of in vitro tested rods, the polymeric compon ent was unchanged in 2 weeks while the drug leached out, leaving voids behi nd. In vivo, however, the morphology of the implant was significantly modif ied within 6 weeks post-implantation. Since a substantial degree of the in vivo drug release was complete within 1 week, we believe that dissolution o f the drug must be the predominant mechanism through which the drug release is controlled. (C) 2000 Elsevier Science Ltd. All rights reserved.