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Orthopaedic implants, such as joint prostheses and internal fracture-fixation devices, are increasingly used. In contrast to transplants, such foreign bodies are accepted by the organism without immunosuppression. Nevertheless, each type of implant increases the risk of local infection [1]. Whereas biomechanical aspects of internal devices have steadily improved, the high susceptibility to infection remains a problem. Despite preventive measures regarding infection control and antibiotic prophylaxis, implant-associated infections still occur. Such infections are caused by surface-adhering microorganisms forming a biofilm. Bacteria colonizing an implanted non-living surface persist as aggregated microbial cells surrounded by a polymeric self-produced matrix containing host components [2]. Microbial aggregates resist not only host defence mechanisms, but also most antibiotics [1–3]. During the last two decades, a paradigm shift regarding treatment concepts has been observed. According to the classical view, implants have to be removed for complete eradication of biofilm bacteria. According to novel concepts, this dogma is outdated, at least in a significant number of cases. After correct microbiological diagnosis, and if proper antibiotics are rapidly administered, many orthopaedic devices can be kept in place after thorough debridement surgery [4].

In this themed section of CMI, three unresolved issues regarding orthopaedic biofilm infections are covered. First, it is still not clear whether the type of material plays a crucial role regarding the propensity for infection. Second, the role of molecular diagnostics is not yet established for routine diagnosis of implant-associated bone infection. Third, there are still many open questions regarding antimicrobial therapy of such infections, because large controlled clinical trials are missing.

For obvious reasons, companies developing orthopaedic devices are more interested in biomechanical research than in issues regarding prevention of infection. Periprosthetic joint infection occurs not only during implantation, but throughout life by the haematogenous route [5]. Thus, perioperative antibiotics protect only during a minimal period at risk. Therefore, knowledge about the influence of biomaterials on the propensity for infection is clinically relevant. Rochford et al. [6] from the AO Foundation Research Institute (Davos, Switzerland) reviewed this question. They report the interaction of different materials in vivo and in animal models. However, clinical data showing a reproducible and distinct propensity of different biomaterials to infection are missing. It is conceivable that proteins (e.g. fibronectin, fibrinogen or vitronectin) covering the material immediately after insertion in the organism are more important for bacterial adhesion than the material itself [7].

In about 5–15% of patients with periprosthetic joint infection, no microorganism can be detected. In more than half of the cases, patients received previous antibiotics [8]. Because correct long-term antimicrobial therapy depends on the identification of the correct microorganism, more sensitive diagnostic methods are needed. Unfortunately, with molecular methods no comprehensive susceptibility pattern is available. Therefore, these tests will not replace microbiological culture techniques in the near future. Broad-range PCR has two major drawbacks when used in patients with periprosthetic joint infection. First, its sensitivity is low and second, polymicrobial infection is difficult to detect with broad-range PCR targeting the 16S rRNA sequence without separating the amplification products by cloning or using gradient gel electrophoresis. Lévy & Fenollar [9] reviewed the role of molecular diagnostics in implant-associated bone and joint infection. Because the efficiency of these methods heavily depends on the correct technique, these experienced authors present crucial pre-analytical and analytical aspects of the entire process. They conclude that molecular techniques should not replace conventional culture, but mainly be used in culture-negative cases. In the near future, not only broad-range PCR followed by sequencing, but also real-time multiplex PCR assays with appropriate primers will be available. For the time being, commercially available multiplex PCR tests are not yet ideal, because they are not developed for use in patients with periprosthetic joint infection, and hence, lack relevant primers.

Antimicrobial therapy of implant-associated infection is mainly based on expert opinions. Guidelines based on controlled studies are missing. There are still many open questions, for example regarding the need for initial intravenous therapy, the importance of bone penetration, and the role of rifampin in non-staphylococcal grampositive microorganisms. Staphylococci are the most frequent microorganisms causing bone and joint infection. Linezolid and daptomycin are antimicrobial agents with activity on resistant gram-positive microorganisms. Unfortunately, both substances are not yet approved for use in bone and joint infection. Novel antibiotics are generally initially approved for frequent indications such as skin and soft tissue infections, lower respiratory tract infections and bacteraemia. Therefore, after introduction of a novel antibiotic to the market, several years of off-label use are required in order to get enough published data for the evaluation of these drugs in bone and joint infection. These therapeutic questions are reviewed in the article by Sendi & Zimmerli [10].

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The author has no conflict of interest related to the present article.

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