Some serious issues over the perceived role of biomaterials and medical devices in the cause and control of infection have been raised. This article discusses some of the implications of claims and counter-claims concerning these matters.
Biomaterials and cause of infection
In the United States (US), a product liability and medical malpractice case in which I was involved, concerned a lady who was unfortunate enough to be diagnosed with cancer of the spine. She subsequently had multiple surgical interventions of mixed outcomes and eventually became paraplegic. Central to the case was the fact that following one of the procedures, an area of the spine became infected and this was extremely difficult to treat. Part of the problem was that in one surgical procedure a metal cage and bone grafts had been used to produce bone fusion and stability in the region where the tumour had been excised. Because this was not successful, further procedures had to be performed, one of which involved the use of a polymeric sealant to assist in wound healing around the spine. The claim was made that, amongst other factors, the polymer itself caused the infection.
This was not the first time that a biomaterial or a medical device has been blamed for causing an infection, and it will not be the last because medical device companies constitute an apparently deep pocket when personal injuries are involved. However, it is clear that some essential truths need to be re-stated. For legal reasons I cannot discuss the precise details of this liability case, but general points will suffice. The first point is that biomaterials do not cause infection; it is bacteria that do that. This may sound a trivial and obvious point, but it is all too often ignored. There are several ways in which biomaterials and medical devices may influence the course and outcome of an infection, but this is not the same as being the cause in the first place. The device can be a carrier of bacteria, a situation that we obviate as far as possible by the process of sterilisation; well documented process validation with respect to sterilisation is a powerful part of the defence in product liability cases. In addition, we know that the presence of biomaterials, or indeed any foreign object in a wound site, can alter the pathogenicity of bacteria by altering the microenvironment in which any invading bacteria find themselves. The layer of adsorbed protein, often referred to as biofilm, may encourage bacterial colonisation and perhaps migration; this problem is specifically associated with indwelling catheters and their susceptibility to infection. It is also possible for the tissue response to an implanted biomaterial, which will involve a level of inflammation and the release of a variety of active chemicals, may influence the ability of the host to deal with bacteria as it normally would. The mechanisms by which the biomaterial, the host tissues and bacteria interact are complex and not fully understood. At the risk of repetition, I categorically state again that biomaterials do not cause infection. That is also an extremely good defence.
Implanted devices and late infection
The one area where there is a great concern about the interplay between implanted devices and infection, and which leads to my next point of discussion, is the risk of late infections around devices through the systemic distribution of bacteria following infection elsewhere in the body. For many years, it has been considered necessary to protect certain vulnerable patients with implanted medical devices against life threatening infections. By far the most important group involves individuals with prosthetic heart valves, who are especially at risk of acquiring infective endocarditis. This bacterial infection has an incidence in the region of 1–2% of patients with valves and it is usually fatal. There are many risk groups involving patients who have some type of heart condition, and it is those with heart valve disease and those who have undergone valve surgery who have been considered to be at highest risk. The endocarditis usually follows a bacteremia, which may itself be the consequence of an infection in the gastro-intestinal or urinary systems. There is little that can be done to prevent endocarditis following an acute infection in those systems, but there is one situation in which endocarditis has been considered preventable and that is following a planned dental procedure. Here, it has been common practice for dentists to prescribe antibiotics for any patient thought to be at risk from infective endocarditis, including those with prosthetic valves.
Many years ago, I used to be involved in research into issues of biomaterial-bacterial interactions, but not in recent times. My interest was re-awakened, however, by the legal case mentioned above and by an experience when sitting in a dental office in the US. A large part of a molar tooth broke away while I was in China recently and it was necessary to have this tooth examined. Attending for the first time a dental clinic in North Carolina, I had to fill in some detailed forms, including relevant medical history and I included in my responses the fact that I had had a hip replacement four years previously. I was surprised to hear that I was required to have “pre-medication,” that is, prophylactic antibiotic treatment before the dentist could perform any procedure in my mouth. This apparently is routine practice in the US as a form of insurance for anyone who has had a total joint replacement. I had a friendly discussion with the dentist and explained to him that there was no evidence of a causal relationship between dental treatment and prosthetic hip replacement, and we agreed that we would proceed without the antibiotics. On re-examining the literature and clinical guidance I now find that there is little evidence of any link between implantable devices and late infection. Even in the area of heart conditions and infective endocarditis the trend moving is away from routine prophylaxis. This is because not only is there little evidence of any connection, but also because any premedication of this type is unlikely to be effective anyway. In 2008, the United Kingdom’s the National Institute for Health and Clinical Excellence produced a report on this matter and issued clear guidance.1 Although some risk groups remain for which antibiotic coverage is still recommended for certain dental procedures, and patients with replacement valves are included, most patients with heart conditions have been removed from the at-risk list.
Antibiotics and medical devices
Although infection can be a tragic outcome of any procedure involving a medical device, the evidence is suggesting that biomaterials per se are not the cause of infection and that caution has to be exercised when trying to prevent infection through the use of antibiotics. It was suggested in the legal case referred to above that antibiotics should have been incorporated into the polymer sealant to minimise the risk of infection. There is no evidence that this would be a clinically or economically effective option. It is true that antibiotics are incorporated into some orthopaedic bone cements, but the situations in which antibiotics can have long term effectiveness in devices will be minimal. There is, of course the broader issue of antibiotic resistance. On passing through Europe while writing this column I noted a number of news items on this subject leading up to the European Antibiotic Awareness Day on 18 November 2009. The European Center of Disease Prevention and Control has issued a statement2 on this matter saying that
if this wave of antibiotic resistance gets over us, we will not be able to do organ transplants, hip replacements, cancer chemotherapy, intensive care and neonatal care for premature babies.
These are strong words and it is recognised that the prophylactic use of antibiotics in relation to infection control in medical devices could only ever represent a minute contribution to overall anti-biotic distribution. However, it would be ironic if an ineffective use of these medicines as adjuncts to medical device procedures hastened their demise as widely effective tools to combat infection.
References
1. UK National Institute for Health and Clinical Excellence, Prophylaxis Against Infective Endocarditis, Clinical Guidance No 64, 2008, www.nice.org.uk [5]
2. European Centre of Disease Prevention and Control, 2009, Antimicrobial Resistance, www.ecdc.europa.eu/en/healthtopics/Pages/Antimicrobial_Resistance.aspx [6], accessed 9 Nov 2009.
David Williams
Morgan & Masterson, Avenue de la Forêt 103, Brussels 1000, Belgium, tel. +32 4 7597 0556,
e-mail: peggy@morgan-masterson.com [7]
www.morgan-masterson.com [8]
Professor David Williams DSc, FREng
Professor Williams retired from the University of Liverpool, after 40 years, at the end of 2007. He retains the position of Emeritus Professor there and now has a series of professorial appointments in the USA, Australia, South Africa and China. In the USA he is Director of International Affairs for the Wake Forest Institute of Regenerative Medicine. He offers consulting services from his company Morgan & Masterson, based in Brussels, Belgium. He is Editor-in-Chief of Biomaterials, the leading journal in the biomaterials field.