Biofilms and Medical Devices

BIOFILMS AND MEDICAL DEVICES

Medical devices have become an essential aspect of patient care, with tens of millions of implantable or indwelling medical devices (such as catheters, endotracheal tubes, artificial joint protheses and so on) used each year in patients worldwide. However, despite the evolution of medical devices and the biomaterials from which they are manufactured, their use in vivo is significantly compromised by their seemingly ubiquitous propensity to succumb to microbial colonization and biofilm formation, otherwise known as medical device-associated infection. Immediately after implantation, the device surface becomes modified by the adsorption of host-derived proteins, extracellular matrix proteins, coagulation products, etc., depending on the site. This ‘conditioning film’ renders the surface of the device favourable for microbial adhesion and is often followed by rapid primary attachment of microorganisms to the material surface and biofilm formation.

The microorganisms responsible for causing medical device-associated infections may be either from exogenous (carers, visitors, healthcare environment) or endogenous sources (via the migration of microorganisms from normally colonized body sites). Although site dependent, the main causative organisms of medical device-associated nosocomial infections are frequently normal skin biota including Staph. aureus and coagulase-negative staphylococci, predominantly Staph. epidermidis, which is the most common causative organism of infections related to intravascular catheters and other implanted medical devices. A number of other key microorganisms have been shown to be significant causative organisms of medical device related nosocomial infections, including Pseudomonas aeruginosa (ventilator-associated pneumonia, VAP), enterococci, Escherichia coli (urinary tract infection (UTI), septicaemia) and Proteus species such as Proteus mirabilis (UTI, device encrustation).

At least half of all cases of health care associated infections are estimated to be due to biofilm-mediated, medical device-associated infections, with medical device use now regarded as the greatest external predictor of health care associated infections. The development of medical device-associated infections generally necessitates the complete removal and replacement of the device, with the level of clinical intervention depending on the nature and site of the device implantation. Systemic antibiotics (often a combination therapy of two or more antimicrobial agents) represent the conventional approach to the treatment of device-associated infections; however, given the high degree of tolerance to antimicrobial challenge that is a feature of biofilm populations, eradication proves extremely difficult and infection relapses frequently occur. This has led to the development of a range of anti-infective and antimicrobial biomaterials for use in device manufacture, though the long-term efficacy of these devices in the reduction of medical device-associated infection is an area of considerable debate.

Health care associated infections typically occur at four main body sites (urinary tract, respiratory tract, surgical sites and bloodstream infections), three of which (UTI, pneumonia, bloodstream infections) are commonly associated with the use of indwelling devices. Indeed, around 95% of nosocomial UTIs reported are linked to the use of urological devices (mainly urinary catheters), and more than 85% of nosocomial respiratory infections (mainly VAPs) are device-related. Central venous catheters pose the greatest risk of mortality due to catheter-related bloodstream infections, with incidences in the USA ranging from 100 000 to 500 000 cases annually, resulting in more than 25 000 deaths per year. Although these represent the most common device-associated infections, it is worth noting that all types of implantable medical device are susceptible to infection: for example, peritoneal catheter infections in peritoneal dialysis, orthopaedic implant infections, and biofilm formation on prosthetic heart valves. In addition to patient morbidity and mortality, device-associated infections impose significant financial burdens on healthcare providers, related primarily to increased hospitalization time and associated care costs. Despite this, the use of and dependence on implantable, indwelling medical devices increases annually, correlated to an increasing ageing population in industrialized nations.