In-vitro and in-vivo study of biofilm disruption strategies for the treatment of prosthetic joint infections

Poilvache, Hervé [UCL]

Prosthetic joint infection (PJI) is a devastating complication of joint replacement surgeries, affecting 0.5 to 2% of patients following a hip or a knee arthroplasty. Its treatment is complicated by the rapid formation of bacterial biofilms on the implants’ surfaces. Biofilms are bacterial communities enveloped in a complex self-produced matrix that isolates bacteria from their environment, leading to an increased tolerance to antimicrobials. Therefore, new therapeutic options targeting biofilms are in development to improve the outcome of PJI. The objectives of this work were to investigate biofilm disruption using a standard irrigation technique (pulsed-lavage) or an enzyme combination targeting the matrix of the biofilms, and its impact on the susceptibility of bacteria to antibiotics. Pulsed-lavage and the enzymatic combination were studied in two successive in-vitro studies, using a model of biofilms grown on titanium alloy substrates. Our experiments showed that the successive application of biofilm disrupting treatments and antibiotics, used at clinically relevant concentrations, was synergistic. Considering these encouraging results, an in-vivo model of PJI was developed to study the use of the enzymatic combination as an adjuvant to a treatment with debridement, systemic antibiotics, and implant retention. Regrettably, the addition of the enzymatic combination did not appear to improve the outcome of the treatment. However, these experiments open new perspectives to optimize the use of enzymes in this setting, and the tools developed for this work could prove useful to investigate the application of other strategies for the treatment of PJI.