Osteomyelitis - Biofilms

              

 Osteomyelitis is an infection of bone and bone marrow caused by hematogenous or contiguous spread of the organism from local infection and or open traumatic fracture. Acute osteomyelitis frequently evolves into a chronic disease. The term cure is not used since the bone infection may relapse after many years of successful remission. In this viewpoint, osteomyelitis behaves much like a benign tumor, in that, it rarely kills, but tends to return without complete ablation. Furthermore, the management of osteomyelitis involves diagnosis, staging, treatment, and reconstruction, using methods similar to those used in tumor surgery. The present section will discuss the pathogenesis, diagnosis, and treatment of osteomyelitis.

Pathogenesis and Biofilms

               The precise definition of a biofilm has continued to evolve as this area of research progressively expands. Today a biofilm can best be described as a dynamic and heterogeneous community of sessile bacteria which are surrounded by an extra cellular matrix of polymers. These bacteria by definition exhibit an altered phenotype in comparison to their free floating planktonic counterparts. This entire conglomeration, known as the biofilm, is adherent to an inert surface (e.g. plates, bony sequestra, or a prosthetic joint replacement). The structure of a biofilm consists of three basic elements: bacteria, extra cellular matrix, and other interstitial metabolic components. The biofilm is a dynamic microenvironment with continual ebbs and flows. Pockets of grouped sessile bacteria are surrounded by exopolysaccharide glycocalyces. These micro colonies are found with interspersed water channels which provide for the flow of various metabolites, chemicals and nutrients. Biofilms appear to tend to form in areas of high mechanical shear. Here the colonies formed show remarkable resistance to mechanical breakage.

               Numerous bacterial species have been described to form biofilms. Most commonly in orthopaedic surgery, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, and Pseudomonas aeruginosa are the underlying causative organisms of musculoskeletal infections. The clinical significance of biofilms in orthopaedic surgery lies in the fact that biofilms form on implanted hardware and cause infections that are difficult to eradicate. This apparent antibiotic resistance does not appear to be mediated through traditional cellular modes of antibiotic resistance such as efflux pumps, deactivating enzymes, or target protein mutations. The extra cellular glycocalyx matrix portion of the biofilm constitutes one potential area of antibiotic resistance. In some instances, diffusion from outside of the biofilm inwards to the sessile bacteria may present a barrier which limits the efficacy of a given antibiotic. Likewise specific antibiotics may be bound by the extra cellular portion of the biofilm and hence rendered ineffective. The polymeric extra cellular portion of the biofilm can also serve to create an altered microenvironment in which certain compounds may be less able to exert specific effects. Sessile bacteria within biofilms appear to be phenotypically different from their planktonic counterparts.

               Sessile bacteria have a slower rate of growth. From an evolutionary perspective it appears that these cells serve to function like spores, which are more adept at persisting over time but are also less metabolically active. As such, these less metabolically active cells naturally are less susceptible to chemotherapeutic agents designed to limit cell reproduction. This ability of sessile bacteria to persist may have a role in chronic infections. As bacteria survive for longer periods there is more opportunity for acquiring traditional methods of cellular antimicrobial resistance. This combined with the unique properties of biofilm resistance can lead to an infection which is difficult to conquer. As planktonic bacteria are intermittently released from the biofilm over time, there are multiple opportunities for the development of a secondary infection. As the biofilm matures, there is a greater probability that the planktonic bacteria which are released will be better equipped for survival.

               Several immunologic proposals have been made which contribute to our understanding of biofilms and the role that they play in device-related infections. A foreign material elicits a cellular and/or humoral immune response, however, if this response persists over time, the macrophages can cease there normal activity, so, as the biofilm develops and the immune system fails to clear the infection, valuable chemical mediators are expended. Later when specific enzymes are needed, the reserves are dry and hence a clinically symptomatic infection may occur. Similarly, as the immune system reacts but is unable to attack sessile bacteria hidden within the auspices of a biofilm, frustrated phagocytosis may occur. Reactive oxidative species can then be released which cause damage to normal intact tissues which are adjacent to the infection-causing biofilm.