Antibiotic-loaded poly(trimethylene carbonate) degradation, release and staphylococcal biofilm inhibition

Infections localised to bone (osteomyelitis) rapidly progress to a chronic state in which bacteria form organised communities (biofilms) where they are protected from host defences and antibiotic therapy. Treatment requires surgery followed by systemic and/or local application of antibiotics. With local application, an antibiotic delivery device is employed to ascertain high local antibiotic concentrations. Historically, such devices are made out of polymethylmethacrylate (PMMA; bone cement), but more recent research is focussed on biodegradable alternatives. In this thesis we investigated the possibilities of poly(trimethylene carbonate) (PTMC), used as a biodegradable antibiotic delivery system in the possible treatment of osteomyelitis. PTMC has advantages over conventionally used PMMA because the former does not require secondary surgical removal and because additional antibiotics can be applied. Specifically, the studies included in this thesis are in vitro (laboratory) studies focusing on release of antibiotics from PTMC, bacterial biofilm inhibition, and evaluating new antibiotic regimens for incorporation in PTMC to target biofilms of treatment recalcitrant strains (e.g. Methicillin-resistant Staphylococcus aureus, MRSA).

We demonstrated that, compared to conventional PMMA beads, PTMC discs released similar proportions of incorporated antibiotic gentamicin, resulting in similar inhibitory effect on biofilm formation by Staphylococcus aureus. The antibiotic vancomycin - frequently employed in MRSA infections, but not suitable for use in PMMA - is released from PTMC by superior release kinetics. Additionally, PTMC loaded with the antibiotic combination rifampicin and vancomycin showed especially efficacious in targeting biofilms from difficult to treat strains such as antibiotic resistant MRSA.

In conclusion, PTMC is a very promising biodegradable antibiotic delivery system for the local treatment of chronic osteomyelitis.