Getting excited about exit sites in peritoneal dialysis?

Despite all the attention given to issues such as adequacy of clearances, ultrafiltration failure, and lack of home support, peritonitis remains the leading cause of technique failure in most peritoneal dialysis (PD) centers (1,2). Furthermore, recent audits from a number of regions suggest that peritonitis rates in unselected centers are often higher than those reported from motivated centers of excellence. For example, Brown and colleagues looked at all 10 PD units in Scotland between 2001 and 2007 and found that the peritonitis rate was 1 every 19.9 months, and Ghali et al. (3,4) from the Australia New Zealand Registry reported an almost identical rate of 1 in 20 months from their 72 centers between 2003 and 2008. These rather disappointing rates do contrast with better results in Canada and France, but the latter studies are based on more selected units rather than a comprehensive audit (5,6). Clearly, peritonitis is a problem that has not gone away. Peritonitis is generally acquired by one of three major routes. These are touch contamination by the patient during connection procedures, migration of organisms from the exit site through the catheter tunnel, and transmural migration from the gut into the peritoneal cavity (7). The first great breakthrough in preventing peritonitis occurred with the widespread introduction of Y set and double bag continuous ambulatory peritoneal dialysis connection systems in the 1980s and 1990s. Rates were typically 50% lower in randomized trials testing these systems, and there was a sense of optimism that peritonitis as a problem was largely solved when their use became widespread (8,9). Rates of peritonitis undoubtedly fell, but this was mainly because of a decline in cases caused by touch contamination organisms such as Staphylococcus epidermidis (10). These, however, were the mildest cases of peritonitis with the lowest rates of catheter loss and technique failure. The second significant advance occurred in the last 15 years and was related to peritonitis that occurred via the catheter tunnel in association with exit site colonization and infection, typically with Staphylococcus aureus and Pseudomonas aeruginosa organisms. Landmark studies proved that S. aureus peritonitis was related to colonization of the patient, and of the exit site, by this organism (11). Subsequently, effective prevention strategies with locally applied mupirocin and gentamicin antibiotic creams were shown to reduce exit site infection (ESI) and peritonitis rates (12,13). Intriguingly, one randomized trial showed a decline in gram-negative non-Pseudomonas peritonitis, which had previously been thought not usually to enter the peritoneal cavity via the exit site and tunnel (13). Despite these encouraging studies, uptake of these strategies has not been universal, and peritonitis rates do not appear to have fallen in the same way that they did when Y sets were introduced (1,2,10). This raises some questions. Why are these preventative local strategies not being more widely used? Is it physician ignorance or skepticism? Or are the strategies not as effective as the trials have suggested? Is the underlying hypothesis connecting exit site colonization and infection to peritonitis flawed in some way? Against this background, van Diepen et al. (14) published an analysis of the relationship between ESI and peritonitis in this issue of CJASN. They use data from their recently published randomized controlled trial that compared exit site application of polysporin and mupirocin (15). This study enrolled 201 patients and found no difference in rates of peritonitis, tunnel, or ESI between the two groups. The authors then investigated the risk of developing peritonitis in the days immediately after diagnosis and treatment of an exit site infection. They found that the risk is increased .10-fold in the first 15 days, .6-fold in the first 30 days, and almost 5-fold up to 60 days. This would appear to be impressively clear evidence supporting the hypothesis that ESI is a cause of peritonitis. The authors, however, raise some caveats. They note that in only one case did peritonitis caused by the same organism occur after an ESI. Frequently, there was a discrepancy between the organism cultured from the exit site and that grown from the subsequent peritoneal effluent. They also report that the aggressiveness with which an ESI was treated, in terms of systemic versus topical antibiotics, did not alter the subsequent risk of peritonitis. These findings lead the authors to question the underlying notion that the ESI actually causes the peritonitis. It is important to question underlying dogma in clinical medicine and dialysis is an area where research studies challenging dogma have often yielded surprising results. van Diepen et al. are to be congratulated for asking and attempting to answer a question that many would have considered self-evident. However, perhaps they are second guessing their own impressive findings to an excessive degree! Division of Nephrology, University of Western Ontario, London, Ontario, Canada