**3. Incidence, pathogenesis and bacteriology of access-related infections**

Although the incidence of catheter-related bacteraemia is variable, the mean reported incidence is 3 episodes per 1000 catheter days (Dryden et al., 1991; Moss et al., 1990; Saad, 1999; Mokryzcki et al., 2000; Mokrzycki et al., 2001). Data from the HEMO study (Eknoyan et al., 2008) indicates that patients with central venous catheters have an increased relative mortality risk of 3.4 when compared with patients with AVFs (relative mortality risk of 1.4). The burden of catheter-related infection is high, with reported rates of metastatic infectious complications (e.g. osteomyelitis, endocarditis, septic arthritis or epidural abscess) of between 10% and 40% (Marr et al., 1997; Maya et al., 2007; Neilsen et al., 1998). *S. aureus* is responsible for the majority of vascular access infections, accounting for 70-90% of cases (Del Rio el at., 2009; Gould, 2007).

#### **3.1 Catheter-related bacteraemia**

Gram-positive species are the culprit organisms in 61-95% of cases of catheter-related bacteraemia. In the prospective study by Hoen et al (1998), the most common causative organism was *S. aureus*. Coagulase-negative staphylococcal bacteraemia was almost as common as that caused by *S. aureus*. *Escherichia coli* and other aerobic gram negative bacilli were the next most commonly isolated organisms. The presumed portal of entry for these organisms was via the vascular access. In this study, 6 deaths were directly attributable to bacteraemia. The most common causative organisms under these circumstances were *S. aureus* and *Pseudomona*s with equal occurrence, and other Enterobacteriaciae making up the remainder of isolated agents (Hoen et al., 1998).

Catheter-related bacteraemia may arise via two paths: (a) direct spread of microorganisms from the skin along the outside of the catheter leading to contamination of the bloodstream; or, (b) colonisation of the inner lumen of the catheter leading to the formation of biofilm and direct migration of organisms into the bloodstream. A biofilm is a multi-layered cell cluster with a strong propensity to adhere to polymer surfaces and provides a protected niche environment for microorganisms with physical barrier protection against antibiotics. Within the biofilm, bacteria exhibit increased growth rates, a higher cell density and more active gene transcription. This further contributes to the heightened resistance of bacteria to antibiosis (Fux et al., 2003). Even in the absence of overt infection, microbial colonisation of catheters may engender a chronic inflammatory state, which in turn increases the risk of erythropoietin-resistant anaemia, malnutrition and cardiovascular disease (Barraclough et al., 2009).
