After 15 years of active research and development, CERAVER, announce the beginning of a large multicentric clinical study

The number of hip replacements performed in France is constantly rising. In 2009, according to the ATIH (Agence Technique de l’Information sur l’Hospitalisation — Technical Agency for Hospital Admissions Information), 125,212 hip replacements were implanted in France, including 91,742 for conditions other than recent injuries. In 2014, this surgery concerned 138,582 patients, including 103,425 for conditions other than recent injuries, i.e. an increase of almost 10% in 4 years.

While the first studies reported infection rates of around 10% [1], following the introduction of various prophylactic procedures, the rate of total hip replacement infection (THRI) is now less than 1%. This infection rate varies depending on departments.

An analysis of Scandinavian registries demonstrates that 7 to 11% of hip implant revisions were performed due to infection [2, 3]. A recent study also demonstrated that the hypothesis of infection must always be checked in the event of apparently aseptic loosening, i.e. without any evident signs of infection of the implant [4].

In France, infections on hip implants therefore concern around 1,300 patients per year. These are serious infections, which are a source of morbidity and can even be fatal. 10 to 15% [5] of patients already treated for a hip replacement infection present a recurrence. Treatment is medical and surgical, and multidisciplinary. It usually includes replacement of the implants in one or two surgical procedures and long-term antibiotic therapy, first intravenous then oral [6]. The patient is therefore exposed to complications related to the various surgical procedures and the side effects of the antibiotics used at high doses and over a long period. A French study [7] demonstrated that the cost of a septic revision was 3.6 times higher than that of a primary implant.

The method of implant contamination is either intraoperative, or haematogenous, hence the currently accepted classification into 4 groups, according to Tsukayama [8]:

  • Early postoperative infection: infection within the first month following joint replacement;
  • Late chronic infection: developing insidiously, manifesting more than a month after the surgery;
  • Acute haematogenous infection: sudden onset in a patient who was doing well until then and in whom bacteremia is suspected or confirmed. The signs usually develop late, with a symptom-free interval of more than 1 month. The bacteria involved are generally virulent microorganisms (Staphylococcus aureus, streptococci, Gram-negative bacilli, etc.). It is necessary to look for a port of entry. Isolation of the microorganism at the port of entry and/or in blood cultures confirms the diagnosis;
  • Unknown infection: revealed by positive intraoperative cultures during revision surgery on a loosened implant considered to be aseptic [9].

The difficulty in treating these infections is largely due to the bacterial “biofilm” that forms very early on following bacterial contamination of the implant [10]. Following insertion of the implant, a ”race for the surface” begins within a few seconds, between the proteins of the host, involved or otherwise in cellular and bacterial adhesion mechanisms, and the cells and the bacteria present at the surgical site. A protein layer forms in a few minutes on the implant surface, with its composition being key to the good tolerance of the implant by the body and its biointegration. If the protein layer is composed of proteins in arrangements promoting the adhesion of bacteria to the implant, then rapid bacterial multiplication leading to infection can occur. The bacteria quickly develop a survival strategy by secreting a bacterial biofilm protecting them from the host’s immune reactions and making it difficult for antibiotics to reach them.

To prevent the development of such infections, it is therefore necessary to limit or even prevent the formation of the bacterial biofilm, at the same time controlling the protein response in order to enable osseointegration of the implant.

The Actisurf coating consist of a chemistry modification of the implant surface by grafting on an anionic polymer : the poly Sodium Styrene Sulfonate ([poly(NaSS)]. This polymer has an anti-adhesion action on bacterias and does not modify the osteointegration.

After 30 years of research, the ANSM authorised to conduct clinical trials. First implantation already started in France and soon a similar protocol will be conducted in Germany.

 

 

[1] Wilson PDJ, Amstutz HC, Czerniecki A, Salvati EA, Mendes DG. (1972) Total hip replacement with fixation by acrylic cement. Journal of Bone and Joint Surgery, 54-A, 207-236.

[2] Puolakka TJ, Pajamaki KJ, Halonen PJ, et al. The Finnish Arthroplasty Register: report of the hip register. Acta Orthop Scand 2001;72:433-41.

[3] Lucht U. The Danish Hip Arthroplasty Register. Acta Orthop Scand 2000;71:433-9.

[4] Parvizi J, Suh DH, Jafari SM, Mullan A, Purtill JJ. Aseptic Loosening of Total Hip Arthroplasty: Infection Always Should be Ruled Out. Clin Orthop Relat Res. 2011 Mar 2. [Epub ahead of print]
[5] A. Lortat-Jacob, G. Nourissat, B. Heym. Réinfection avec changement de germe après réimplantation de prothèses pour infection A propos de 13 cas. Revue de chirurgie orthopédique2003, 89, 297-303

[6] A. D. Toms, D. Davidson, B. A. Masri, C. P. Duncan. The management of peri-prosthetic infection in total joint arthroplasty. J Bone Joint Surg [Br] 2006;88-B:149-55.

[7] Klouche S, Sariali E, Mamoudy P. Total hip arthroplasty revision due to infection: a cost analysis approach. Orthop Traumatol Surg Res 2010;96:124-32.

[8] Tsukayama DT, Estrada R, Gustilo RB. Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections. J Bone Joint Surg 1996;78-A:512-23.

[9] Costerton JW. Biofilm theory can guide the treatment of device-related orthopaedic infections. Clin Orthop Rel Res. 2005;437:7-11.

[10] Gristina AG, Naylor P, Myrvik Q. Infections from biomaterials and implants: a race for the surface. Med Prog Technol. 1988-1989;14(3-4):205-24.