Principle of local antibiotic therapy

During a BJI, antibiotics are administered by the “systemic” route, i.e. orally or intravenously. Only a small proportion of what is administered systemically penetrates the bone. For the bone to heal, it is necessary to prolong the antibiotic therapy for several weeks, generally 6 to 12 weeks. Local antibiotic therapy is an emerging field. The idea is to deliver a large quantity of antibiotic locally, using a “carrier” that stabilises the antibiotic and diffuses it over several days or weeks. High local concentrations of antibiotic can potentially trigger “anti-biofilm” activity. The complementarity of systemic antibiotic therapy (in red in the figure below) and local antibiotic therapy (in yellow) results in theoretically “optimal” pharmacokinetics.

Principle of antibiotic-loaded cements

Bone cements are devices widely used in orthopaedics. They are made of polymethyl methacrylate (PMMA) and have been used for decades for prosthesis fixation and to improve its integration within the bone of the patient.

Since the cement is a foreign body, it must be removed when the prosthesis is changed. In recent years, some manufacturers have added antibiotics such as gentamicin, vancomycin or clindamycin to the composition of their cement. These antibiotics are stable in this cement and are diffused in high concentration over several weeks.

The use of antibiotic-loaded cements is quite frequent during a change of prosthesis. These cements are used as « spacers » in septic pseudarthrosis, to temporarily fill a loss of substance with bone graft.

Example of pharmacokinetics (in red) from gentamicin released by antibiotic-loaded bone cement. Local concentrations are extremely high initially (logarithmic scale) then decrease over time. In green and blue, the respective pharmacokinetics of gentamicin and vancomycin released by an innovative cement containing these two antibiotics, with very high initial concentrations, far above bactericidal concentrations, lasting for several days.

Cements that release a combination of antibiotics are not currently reimbursed, as there are no clinical studies reporting their effectiveness, to date.