Abstract
BackgroundOsteomyelitis is an acute or chronic inflammatory process of the bone following infection with pyogenic organisms like Staphylococcus aureus. Tobramycin (TOB) is a promising aminoglycoside antibiotic used to treat various bacterial infections, including S. aureus. The aim of this study was to investigate the efficacy of tobramycin-loaded calcium phosphate beads (CPB) in a rabbit osteomyelitis model.MethodsTobramycin (30 mg/mL) was incorporated into CPB by dipping method and the efficacy of TOB-loaded CPB was studied in a rabbit osteomyelitis model. For juxtaposition, CPB with and without TOB were prepared. Twenty-five New Zealand white rabbits were grouped (n = 5) as sham (group 1), TOB-loaded CPB without S. aureus (group 2), S. aureus only (group 3), S. aureus + CPB (group 4), and S. aureus + TOB-loaded CPB (group 5). Groups infected with S. aureus followed by CPB implantation were immediately subjected to surgery at the mid-shaft of the tibia. After 28 days post-surgery, all rabbits were euthanized and the presence or absence of chronic osteomyelitis and the extent of architectural destruction of the bone were assessed by radiology, bacteriology and histological studies.ResultsTobramycin-loaded CPB group potentially inhibited the growth of S. aureus causing 3.2 to 3.4 log10 reductions in CFU/g of bone tissue compared to the controls. Untreated groups infected with S. aureus showed signs of chronic osteomyelitis with abundant bacterial growth and alterations in bone architecture. The sham group and TOB-loaded CPB group showed no evidence of bacterial growth.ConclusionsTOB-incorporated into CPB for local bone administration was proven to be more successful in increasing the efficacy of TOB in this rabbit osteomyelitis model and hence could represent a good alternative to other formulations used in the treatment of osteomyelitis.
Highlights
Osteomyelitis is an acute or chronic inflammatory process of the bone following infection with pyogenic organisms like Staphylococcus aureus
Development of new delivery systems for antibiotics using biomaterials like calcium phosphate beads (CPB) will remove S. aureus from infection sites effectively, but can potentially revert the damages inflicted on the bone by subsidizing mineral components, which is advantageous to new bone formation
Rabbits were divided into five groups with four animals in each group and the details of grouping are as follows: group 1—normal control; group 2— untreated group implanted with TOB-loaded CPB; group 3—untreated group inoculated with S. aureus; group 4— treated group implanted with CPB and inoculated with S. aureus and group 5—treated group implanted with TOBloaded CPB and inoculated with S. aureus
Summary
Osteomyelitis is an acute or chronic inflammatory process of the bone following infection with pyogenic organisms like Staphylococcus aureus. Treatment of osteomyelitis with local administration of antibiotics using different delivery system, e.g. biodegradable microsphere containing TOB, PMMA beads containing TOB, in combination with systemic antibiotics are some of the choices of treatment [13, 14]. While the use of beads have shown considerable effectiveness in the treatment of osteomyelitis, disadvantages such as poor discharge of antibiotics, the inability to incorporate many useful antibiotics because of heat-instability, involvement of secondary surgery in the removal of cements and lack of biodegradable qualities makes them unviable treatment options [16,17,18]. Development of new delivery systems for antibiotics using biomaterials like CPB will remove S. aureus from infection sites effectively, but can potentially revert the damages inflicted on the bone by subsidizing mineral components, which is advantageous to new bone formation
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