Preliminary investigations on a new gentamicin and vancomycin‐coated PMMA nail for the treatment of bone and intramedullary infections: An experimental study in the rabbit

Abstract

To evaluate a new gentamicin-vancomycin-impregnated (2:1) PMMA coating nail as a drug delivery device to treat bone and intramedullary infections, methicillin-resistant Staphylococcus aureus (MRSA) was used to induce femoral osteomyelitis in 20 New Zealand male rabbits. Four weeks after inoculum, the animals were submitted to debridement of infected femur canal, divided into four groups of five animals each and treated according to the following protocols: Group 1, insertion of a steel AISI316 intramedullary nail; Group 2, insertion of a gentamicin-vancomycin-impregnated PMMA nail; Group 3, no therapy; and Group 4 no fixation device and 1-week systemic antibiotic therapy with teicoplanin i.m. At 7 weeks after inoculum, the femurs were explanted sterilely. The radiological score showed that the lowest and best radiological score was observed in Group 2 that was significantly different from the other groups. The highest bacterial load in the femoral canal was found in Group 1, which was significantly different from Group 2 and Group 4 (p < 0.05). Histology showed that Group 2 produced a marked improvement (p < 0.005) of the bone injuries induced by the osteomyelitis in comparison with the other groups (Smeltzer score). The current findings showed that tested device might effectively lead to MRSA infection healing after surgical debridement and immediate implantation. Keywords: PMMA nail; gentamicin-vancomycin coating; intramedullary infections Bone and intramedullary infections are severe complications of fracture management (0-1% for closed fractures and 0-11% for open fractures) 1 and surgical repair (intramedullary nailing 2,3 and lengthening over nails with external fixation 4,5 ) of long bones. A prevalence of methicillin-resistant or gentamicin-resistant Staphyloccous aureus (SA) has been observed, and bone infection with methicillin-resistant SA (MRSA) has increased among patients with implanted orthopedic devices. The current management of these forms of osteomyelitis has two main aims: (a) to limit and resolve the infective process, by removing all foreign material (fixation device), followed by a meticulous debridement of the necrotic and infected area, and by administering systemically prolonged (4-6 weeks) high doses of antibiotics; 6-8 (b) to stabilize the fracture with alternative treatments, mainly external fixators, which are also not without complications. 1,9 The rationale for the long treatment time is based on the observation that revascularization of bone after debridement takes about 4 weeks. 10

Microbiological and pharmacological tests on new antibiotic‐loaded PMMA‐based composites for the treatment of osteomyelitis

“…11 The MRSA inoculum was prepared from overnight cultures grown in Mueller Hinton Broth (MHB) 16 starting from a frozen batch at À808C, and aliquots were prepared. The cells were harvested by centrifugation, washed with saline solution and resuspended to a final density of 5 Â 10 6 CFU/ml of MHB, thus obtaining a volume of 0.2 ml.…”

“…Starting from the current authors' previous experience on a gentamicin-and vancomycin-coated PMMA nails for the treatment of bone and intramedullary infection, 11 new PMMA-based composites have been studied. These composites were enriched with barium sulfate (BaSO 4 ) and tricalcium phosphate (TCP) or with only a slightly higher BaSO 4 concentration.…”

“…11 The schemes of treatments are reported in Table 1. Phase I-Group 1 Eight rabbits were divided into two subgroups of four animals each according to the PMMA-based composites (P-TCP or P-BaSO 4 ) implanted, which were soaked with the antibiotic solution of G and V. These rabbits were treated to evaluate the pharmacological behavior of antibiotic release into femurs from nails prepared with two PMMA-based composites in the short term (3 and 7 days).…”

“…A control group based on PMMA without b-TCP and/or BaSO 4 soaked in a gentamicin/vancomycin solution only was not included in this experimental study, because previous in vitro and in vivo studies performed in the same experimental conditions provided useful data on PMMA cement loaded with the gentamicin/vancomycin combination. 11,15 Briefly, the femoral osteomyelitis was induced by inoculating 0.2 ml (total load of 10 6 CFU) of MRSA into the medullary cavity through the right knee joint. 11 A small stab incision and subsequently a 1-mm drill hole was made in the intercondylar region.…”

“…11,15 Briefly, the femoral osteomyelitis was induced by inoculating 0.2 ml (total load of 10 6 CFU) of MRSA into the medullary cavity through the right knee joint. 11 A small stab incision and subsequently a 1-mm drill hole was made in the intercondylar region. Finally, the drill-hole defect in the intercondylar region was filled with a small block of bone wax (Knochenwachs, B Braun, Aesculap AG & Co., KG, Tuttlingen, Germany).…”