Abstract
Introduction
Open fractures occur with an annual incidence of 11.5 per 100,000 (6900 pa in UK). Infection rates, even with intravenous broad-spectrum antibiotics, remain as high as 22%. For this reason necessary bone grafting is usually delayed until soft-tissue cover of the bone injury is achieved. A biodegradable bone graft that released sustained high concentrations of antibiotics and encouraged osteogenesis, that could be implanted safely on the day of injury would reduce infection rates and avoid reoperation and secondary grafting. The non –union rate (approx 350 pa in UK) should also be reduced. Such a graft, consisting of a PLA/PGA co –polymer and containing antibiotics, is under development and here we report assessment of spectrum and duration of antimicrobial activity and effect of addition of antibiotics on mechanical properties.
Methods
Varying concentrations of gentamicin, colistin, clindamycin and trimethoprim, singly and in combination, were added to the copolymer and test pieces were made. These were then tested using an established method (SPTT) which determines degree and duration of antimicrobial activity as well as risk of emerging resistance. Test bacteria were Staphylococcus epidermidis, Staphylococcus aureus, MRSA and Escherichia coli. Mechanical properties (compressive strength and porosity) were determined using established methods.
Results
A combination of gentamicin (4%w/w) and clindamycin (2.5% w/w) gave best results, with inhibitory activity persisting for over 21 days (the target duration) without emergence of resistance. No significant effect of this combination/concentration on mechanical properties was found.
Conclusions
The experimental PLA/PGA scaffold containing antibiotics showed activity against the common pathogens of open fractures for a period considered long enough to eradicate contamination acquired at or soon after trauma. At the optimum concentration, they had no significant effect on mechanical properties. In vivo performance is currently being investigated in a sheep model.
