**3. Pathogenesis-mechanisms**

The main route of infection in CAUTI is ascending. This happens by two main mechanisms: Firstly, extraluminally through migration of bacteria along catheter surfaces and secondly due to colonization of the catheter bag or contamination of the junction between the catheter and the catheter bag [22, 23].

In an animal model, it was found that in short-term catheterization, less than 7 days, contam‐ ination of the drainage spout or accidental disconnection of the drainage tube resulted in bacteriuria within a short time (32-48 hours). If a strict sterile closed drainage system was maintained, the extraluminal route assumed more importance in the development of bacter‐ iuria; however this pathway was considerably slower (72-168 hours) [22].

In a prospective clinical study, 66% of the infections were extraluminally acquired and 34% were derived from intraluminal contaminants [23]. Gram-positive cocci and yeasts were more likely to be extraluminally acquired than were gram-negative bacilli, which caused CAUTIs by both routes equally. In the same study, there were no significant differences in pathogenetic mechanisms between the two sexes.

Origination of bacteria is from endogenous organisms either from rectum or colonizing the patient's perineum [23-25]. In one of these studies, colonization of periurethral area was more prevalent in women than in men [23].

Bacteria adhere to catheters via a variety of molecules such are fibriae, heamagglutinin or capsular polysaccharide [26]. Once bacteria have attached to surfaces of catheters, they grow in glycocalyx-enclosed microcolonies and produce a biofilm on the catheter surface which is associated with CAUTIs [27]. Studies have shown that bacteria in this microenvironment are resistant to antibiotics for two reasons [28-30]. Firstly, they are metabolically inactive, perhaps due to low concentration of oxygen [28] and secondly, biofilm acts as a physical barrier to diffusion of antibiotics and host defense mechanisms [29-31]. On the contrary, planktonic-free floating bacteria in urine are susceptible to antibiotics [32-33]. It is worth noting that these two populations are not always identical.

Indwelling catheters not only act as a nidus for bacteria but they also cause physical trauma to normal urothelium, they may promote inflammatory reaction, alter metabolic activity and cell proliferation which facilitates bacterial infection [26]. Recently, an in vitro study which used bladder cancer cell cultures found that catheters are involved in disruption of bladder epithelial cell membranes as a result of physical abrasion which was followed by delayed inflammation in response to bacterial infection [34].

Figure 1 presents schematically all the possible mechanisms involved in pathogenesis of CAUTIs.
