Medical Device Link.

MATERIAL MATTERS COLUMN

MRSA, meticillin (formerly known as methicillin) resistant Staphylococcus aureus to most people, and “superbug” to others, is a subject of considerable scientific and public concern. Although first recognised in the early 1960s, MRSA was an uncommon cause of infection for several decades, but it rapidly increased in significance in the 1980s, some strains then becoming of an epidemic nature in the 1990s. Today, the prevalence of MRSA infections is of major concern worldwide, especially within some particular clinical settings such as intensive-care units (ICUs) where patients are especially susceptible and where transmission of bacteria is facilitated by the procedures and techniques used.

A number of interesting points about MRSA have recently emerged which, for the first time, include some serious issues concerning the role of material surfaces in the incidence and treatment of the infection. But first, a few general background points. Staphylococcus aureus is a common cause of bacterial infection. Initially, it was thought that these bacteria would be sensitive to penicillin, but soon some strains were found to be resistant, because they were able to synthesise an enzyme, penicillinase, which broke down the penicillin. Soon the bacteria evolved so that they became substantially resistant to this antibiotic. Meticillin was developed to counteract this phenomenon, but resistance to meticillin has also evolved. As with most bacteria, MRSA can reside asymptomatically on the skin, but it can readily colonise breached or damaged areas such as accidental or surgical wounds, superficial ulcers and deep abscesses, and intravenous lines and other catheters.

Clinical risk factors

As noted above, the ICU is of particularly high risk. A recent study of 249 patients staying in an ICU for more than 48 hours showed that 8.4% developed MRSA infections, primarily with bloodstream infection, but also pneumonia and surgical-site infection.¹ The main risk factors were intra-abdominal and orthopaedic pathologies, mechanical ventilation, central venous catheter insertion, total parenteral nutrition, previous antibiotic use and the presence of more than two patients in the same ICU with nasal MRSA colonisation. It does not take too much imagination to detect a link to mechanical and invasive medical devices and biomaterials. In a study of MRSA in a urological ward in a hospital in the United Kingdom,² approximately 1% of patients developed a MRSA infection per annum, the commonest sites being a catheter (32%) and open wounds (18%). There is one even more significant biomaterials/medical device related issue. Infective endocarditis has always been a major concern amongst cardiologists and cardiac surgeons because of the significant associated mortality, especially with recipients of prosthetic heart valves. A recent study by an international group of clinicians concerned with endocarditis³ has shown that Staphylococcus aureus has taken over as the most common cause of infective endocarditis, with a predominant bias towards hospital-acquired infection away from community-acquired infection. It was concluded that “MRSA is now encountered internationally as a relatively common cause of infective endocarditis … better treatment and prevention strategies [are required] for this serious and common consequence of medical progress.”

Control of MRSA

In April 2006, guidelines for the control and prevention of MRSA in health-care facilities were published by a joint working party of the British Society of Antimicrobial Chemotherapy, the Hospital Infection Society and the Infection Control Nurses Association.⁴ This is a comprehensive document that is difficult to summarise here. Suffice it to say that although the incidence varies considerably throughout Europe, there has been a dramatic change in recent years with, in the UK, an increase from 2% to 40% during the past 10 years in the prevalence of meticillin resistance among strains of Staphylococcus aureus causing blood-stream infection. There are divergent opinions on the best methods of control to prevent its occurrence in clinical settings. Many have argued that no specific measures are needed, stating that outbreaks are easily resolved because the bacteria are not particularly virulent. However, these guidelines strongly urge specific control measures because of the unequivocal evidence of significant MRSA-acquired hospital infection resulting in additional morbidity, mortality and increased health-care costs. It is, of course, possible that newer antibiotics will be developed that will enhance the ability to treat infected patients; vancomycin is one of the few currently available for this purpose. The recently announced discovery by Merck of a new potential antibiotic from soil samples from South Africa, the molecule platensimycin, is of interest here because this shows no cross-resistance to any major antibiotic resistant bacterial strains, including MRSA.⁵ The control of the spread of the bacteria and their colonisation of surfaces, however, remains of paramount importance.

Air quality is obviously important, and particulate air filtration has been shown to reduce contamination rates.⁶ However, from a materials science perspective, we should be concerned with surfaces. Two separate facts really surprised me, but perhaps they should not have done. More than one-third of computer keyboards and mice used in an ICU were found to be contaminated by MRSA in a major hospital in London, UK.⁷ Three out of 52 reusable tourniquets were similarly contaminated in another London hospital,⁸ it is common in general terms for these tourniquets to be used by phlebotomists 10 times a day for six months without being cleaned.

The potential role of materials and material surfaces

David Williams Clinical Engineering Department, Royal Liverpool University Hospital, Liverpool L69 3BX, UK, tel. +44 151 706 5606 fax +44 151 706 5803, e-mail: dfw.ce@liverpool.ac.uk

Attention is at last being paid to the role of material surfaces. A recent publication has shown that stainless steel, commonly used for surfaces in clinical settings, is not good at resisting colonisation by MRSA, whereas copper was highly effective.⁹ With implantable devices, there are also signs of some developments. A hydroxyapatite–vancomycin bone cement has been shown to inhibit MRSA in mice;¹⁰ and nanoparticulate silver bone cement has been shown to be effective in vitro against MRSA, whereas the conventional gentamycin bone cement is not.¹¹ For catheters, Hirose et al.¹² have shown that the slow release of growth factors from a polyester surface can reduce MRSA colonisation. In June 2006, W.L. Gore announced the development of a polymer mesh containing silver and chlorhexidine that was effective in controlling MRSA and could be used for hernia repair and similar procedures.¹³ I suspect that these are only the beginnings of an important series of material developments. So far it has largely been the known variations of antibacterial agents formulated as materials or material surfaces (that is, silver, copper, chlorhexidine) that have been used, but the biology of bacterial colonisation together with surface science, possibly with the help of nanotechnology, should lead to significant improvements in our fight against MRSA.

Professor David Williams DSc, FREng is Professor of Tissue Engineering at the University of Liverpool and Director of the UK Centre for Tissue Engineering located in the Universities of Liverpool and Manchester. He is Editor-in-Chief of Biomaterials, the leading journal in the biomaterials field. He is Scientific Director of STEPS, the European Commission Framework VI Programme on a Systems Approach to Tissue Engineering Products and Processes. Professor Williams is also a Managing Partner of Morgan & Masterson LLC, a consulting partnership that focusses on global health-care issues.