Reducing infections in the orthopaedic wound

An implant is defined as “an object or material inserted or grafted into the body for prosthetic, therapeutic, diagnostic or experimental purposes”. Examples include sutures, hip or knee replacements, breast implants, heart valves, shunts and central venous catheters. However, such implants pose significant challenges in relation to surgical site infection, as experts pointed out at a recent symposium hosted by Ethicon (a division of Johnson & Johnson Medical). HPA figures show that out of 120,000 total knee and total hip replacements performed in the UK each year, around 1% of hip replacements and 0.5% of total knee replacements become infected. Around 50% of these are deep infections. “Economic analysis has been patchy, but it is estimated that each of these infections costs somewhere between £10,000 and £30,000 – which, when calculated for the whole of the NHS, represents a very large amount of money,” Dr Tamsin Oswald, from the Northumbria Healthcare Trust, pointed out. A consultant microbiologist with a special interest in orthopaedic infections, she commented: “It is extremely difficult and time consuming to treat implantassociated infections once they have become established. The human suffering is significant and infections are associated with higher rates of morbidity and mortality. Moreover, the functioning of the implant is never as good after a patient has contracted an infection,” she continued. She explained that the presence of a foreign body reduces the minimum inoculation to cause infection by around 100,000 times. This means that as little as 100 organisms can cause infection. In addition, because orthopaedic implants are large foreign bodies, they can result in “frustrated phagocytes”. “These phagocytes try to ‘digest’ the foreign body but, because it is too big, they are unsuccessful – cytotoxic enzymes are released, which can damage the surrounding tissue and vasculature. This can lead to detrimental effects on the implant and creates an ideal environment in which bacteria can flourish.”

One of the problems with implantrelated infections is the fact that the implant is devoid of a blood supply – therefore, once an infection becomes established, getting the host defences and/or antibiotics to the implant is a major issue. “There is a hypothesis that, as soon as an implant is inserted, it becomes coated in a protein, containing lygans which attract either the host tissue or bacteria. There is effectively a ‘race to the surface’ and if the host tissue ‘wins’, the host defences are able to fend off the bacteria. However, if the bacteria win this race, and bind to the protein coating first, this will lead to the early stages of infection,” she continued. PMMA bone cements are commonly used as a method of fixation for total joint prostheses but also have a local effect on the host defences – the cement has been shown to have an anti-phagocytic ability in in vitro experiments, she explained. When formulating the PMMA, a thermo reaction is also used – creating heat which can destroy the cortical bone. This, in turn, can lead to devascularised tissue, creating a lush environment in which bacteria can multiply. The formation of biofilm on the implant can further create a low grade inflammatory reaction which can lead to progressive bone loosening and bone loss. Staphylococcus aureus, including MRSA, is one of the most common culprits associated with implant infections, but any organism in the right environment can create a biofilm. A biofilm is an aggregation of microorganisms, in which cells adhere to each other and/or a surface – such as an implant or devitalised tissue. Dr Oswald explained that the biofilm effectively protects the microorganisms underneath from the host defences and antibiotics.

The microorganisms multiply and “mature” in this environment, while “daughter” cells can be shed from the biofilm, which can cause “flare-ups” elsewhere in the host. So what can be done to prevent infection? Approaches include preventing initial device contamination and minimising microbial attachment by altering the implant. Once established, however, methods to kill the biofilmassociated cells, by penetrating the matrix, can be attempted – while strategies to enable earlier detection and intervention, before an extensive biofilm can be created, are currently undergoing research. “There can be direct contamination during the procedure itself. This route accounts for 60% to 70% of implantassociated infections in ultra-clean air environments. In a conventional theatre, it is around 95%,” she commented, adding: “Sources of microorganisms include the patient’s own flora, the surgeon’s skin flora and contaminated operating room air (circulating staff shed skin cells which then contaminate the air). One skin cell can contain hundreds of thousands of bacteria,” she pointed out. She highlighted contaminated instruments as another source: “If instruments are laid out with nothing covering them, the skin cells of circulating staff can land on them and contaminate them. Haematogenous spread can also occur at any time after the implant has been inserted. One paper suggests that this occurs 20% to 40% of the time, although other claims have been much lower.” Patients with Staph Aureus bacteraemia will go on to develop an implant infection in around 34% of cases. Therefore, if a patient presents with septicaemia, the infection needs to be treated very aggressively and very quickly, she warned.