The effects of living distantly from peritoneal dialysis units on peritonitis risk, microbiology, treatment and outcomes: a multi-centre registry study

Peritonitis is a serious complication of peritoneal dialysis (PD), responsible for significant morbidity, and accounting for 30% of technique failures and 21% of infectious deaths in Australian and New Zealand PD patients [1, 2]. Studies of organism-specific peritonitis [3‐13] have described the frequency, predictors, treatments and clinical outcomes of these conditions. However, the impact of distance of residence from PD unit on PD peritonitis has received scant attention.

Recent analysis of the ANZDATA registry by Lim et al.[14] demonstrated greater all-cause mortality in non-metropolitan PD patients in Australia compared with metropolitan PD patients. The remote indigenous PD patients had shorter time to first peritonitis with greater risk of technique failure. Reduced access to specialised medical services and substandard sanitation in remote indigenous patient dwellings have been proposed as reasons for the observed outcomes. This study however defined remoteness based on the Accessibility and Remoteness Index of Australia (ARIA) used by the Australian Bureau of Statistics rather than actual distance to the nearest PD unit.

Distance to the nearest PD unit may influence PD patient outcome by impacting upon access to medical care, delayed diagnosis, delayed dialysate sample processing (leading to higher rates of culture negative peritonitis), compromised management due to the tyranny of distance and ultimately poorer outcomes. These are of particular importance as PD is usually considered a first-choice treatment for end-stage renal disease (ESRD) for patients living in remote areas to avoid relocation [15]. Given that PD peritonitis is a major cause of PD technique failure, addressing the impact of remote residence on PD outcomes, particularly PD peritonitis, is an imperative issue to be addressed. The aim of the current study was to examine the effect of living distantly (≥100 km) from a PD unit on the risk, microbiology, treatment and/or clinical outcomes of PD-associated peritonitis in all Australian PD patients, as recorded in the ANZDATA registry.

The present study represents the largest examination to date of the effect of distance from PD unit on the frequency and clinical outcomes of PD-associated peritonitis. Distant group patients were younger, more likely of indigenous origin and treated by a small PD unit. Time to first peritonitis episode was significantly shorter in this distant group and a greater proportion experienced S. aureus and Corynebacteria peritonitis. Distance from PD unit was independently associated with a higher risk of S. aureus peritonitis. Distant patients were more likely to receive a vancomycin-based antibiotic regimen and be cured with antibiotics alone, and tended to be less likely to undergo catheter removal or permanent haemodialysis transfer.

Greater representation of indigenous patients in remote communities initiating PD and shorter times to first peritonitis episodes in indigenous non-metropolitan patients have been previously reported [14, 16]. However, these investigations defined remoteness based on the Accessibility and Remoteness Index of Australia (ARIA) used by the Australian Bureau of Statistics. In contrast, the present study defined remoteness as living at least 100 km away from the nearest PD unit, which is arguably better suited to reflect accessibility to specialist medical care. The present study also examined peritonitis risk, microbiology, treatment and outcomes in both indigenous and non-indigenous PD patients.

Though culture-negative PD peritonitis did not differ between the two groups, the distant patients were more likely to experience peritonitis due to S. aureus and Corynebacteria and less likely to encounter non-Pseudomonas gram-negative (NPGN) PD peritonitis. Following multivariable adjustment, distance from PD unit was independently associated with a higher risk of S. aureus peritonitis. The reasons for this finding are uncertain, but may reflect a higher rate of staphylococcal colonisation in distant patients or a reduced probability of initiating staphylococcal decolonisation procedures in this group. Chronic carriage of S. aureus has been recognised as being very important in the development of peritonitis in patients on PD since a previous study of Brazilian PD patients found that 95% with both nasal and pericatheter staphylococcal colonization were colonized with the same subtypes at both sites and 100% of patients with S. aureus peritonitis were infected with a subtype which colonized the nares, pericatheter skin or both [17]. A recent meta-analysis of 13 studies (including 3 randomized controlled trials) demonstrated that topical mupirocin application to the nares or exit sites of PD patients reduced the risk of S. aureus exit site infection by 72% (95% CI 0.60-0.81) and peritonitis by 70% (95% CI 0.52-0.81) [18]. Although the ANZDATA Registry does not collect information about topical nasal and/or exit site anti-staphylococcal prophylaxis, it is conceivable that distant patients were less likely to receive such prophylaxis, particularly since the present study demonstrated that patients living more than 100 km away from their nearest PD unit were significantly less likely to receive anti-fungal chemoprophylaxis. A previously published prospective survey of contemporary infection prophylaxis practice in Australia and New Zealand PD units demonstrated poor adherence to national and international best practice guidelines and absence of a uniform, standard practice of exit site care. In particular, 47% had no fixed exit site infection prophylaxis policy, 53% did not routinely prescribe exit site or nasal mupirocin, 57% did not screen for nasal S. aureus and 92% did not co-prescribe anti-fungal prophylaxis [19, 20]. It remains unknown whether this variable adherence to guidelines is influenced by the distance of patient residence from the PD unit.

A vancomycin-based regimen was more commonly used to treat peritonitis in distant patients, than those living within 100 km of their PD unit. This therapeutic decision may have been influenced by the lower probability of hospitalisation of remote patients (probably reflecting logistic considerations) and the convenience of a less frequent dosing requirement for vancomycin, which was more suited to outpatient treatment. Clinical outcomes with vancomycin-based regimens were comparable to those of cephalosporin-based regimens and superior to those of other Gram positive agents.

Indeed, the overall clinical outcomes of peritonitis episodes in patients living at least 100 km away from the nearest PD unit were comparable with those of patients residing closer to nephrologic care. When adjustments were made for differences in baseline characteristics (including an over-representation of Aboriginal and Torres Strait Islanders in remote living patients), distant patients achieved higher cures rates with antimicrobial agents alone and lower rates of catheter removal or permanent haemodialysis transfer. These findings may reflect a stronger incentive to persist with antibiotics in remote living patients rather than removing the PD catheter and transferring to haemodialysis since such an action might have significant social implications for the patient, such as relocation closer to the dialysis service and dislocation from their family and community. Nevertheless, the time to catheter removal did not differ significantly between distant and local patients.

These findings contrast somewhat with a previously published Canadian registry study [15], which found that living remotely from a PD unit was associated with increased risks of PD technique failure and mortality. As with the present study, remote patients were more likely to be younger, Aboriginal and have diabetes mellitus and chronic lung disease. The causes of technique failure and death were not reported in the Canadian study, so it is conceivable that these adverse clinical outcomes could be related to factors other than peritonitis. Moreover, in Canada, 6% of PD patients lived more than 300 km away from their nearest PD unit, such that it is possible that comorbidities may not have been as well captured in these extremely remote living patients. It is also possible that other factors may have contributed to an apparent disparity in the findings between the two studies, such as the local availability of primary healthcare, pathology and telemedicine services in remote regions. On the other hand, another Canadian study found no association relationship between distance of patient residence (≤50 km or > 50 km from the primary dialysis centre in Winnipeg) and peritonitis-free, technique or patient survival rates among patients who were Aboriginal [21]. The apparent disparity in results may relate to the smaller sample size of the Manitoba study (n = 727).

Recently, the BRAZPD study [22] reported paradoxically higher peritonitis rates in patients living within 25 km of a PD unit compared with those living more than 50 km away from the unit (HR 1.40, 95% CI 1.07-1.83). They speculated that these results may have reflected poorer hygiene conditions in urban settings compared with more distant sites. In contrast, urban conditions in Australia are likely to be quite different to those in Brazil. The BRAZPD study also found that larger PD units were associated with a smaller risk of peritonitis [22], whilst our study observed that receiving PD in a small-medium centre (second smallest quartile) was associated with a lower hazard of peritonitis than in the largest quartile. In contrast, no association was observed between PD centre size and peritonitis risk in London [23] or Scotland [24]. Whilst increasing centre size may lead to increased PD experience and improved peritonitis prevention, it is also conceivable that excessively large centres may be operationally inefficient leading to suboptimal infection control procedures and increased peritonitis risks. Alternatively, the results of studies to date may have been limited by residual confounding due to a failure to adjust for other facility variables that contribute to “centre effects.”

The strengths of this study include its very large sample size and inclusiveness. We included all patients receiving PD in Australia during the study period, such that a variety of centres were included with varying approaches to the microbiological diagnosis and treatment of peritonitis. This greatly enhanced the external validity of our findings. These strengths should be balanced against the study’s limitations, which included limited depth of data collection. ANZDATA does not collect important information, such as the presence of concomitant exit site and tunnel infections, antimicrobial susceptibilities of isolated micro-organisms, patient compliance, socio-economic status, individual unit management protocols (including the approaches to staphylococcal decolonisation), duration of cloudy dialysate, laboratory values (such as C-reactive protein and dialysate white cell counts), severity of comorbidities, PD modality (ambulatory or continuous ambulatory PD) at time of peritonitis, disconnect systems used, prescribed PD dialysate (especially icodextrin), antibiotic dosages or routes of antibiotic administration, peritoneal dialysate culture methodology, previous antibiotic exposure for any indication, or local availability of health services in different remote regions (eg nephrologist outreach, primary healthcare, pathology services, telemedicine, etc.). Even though we adjusted for a large number of patient characteristics, the possibility of residual confounding could not be ruled out. Moreover, the relatively small number of patients in the distant group (n = 193) may have reduced the power of the study to identify other independent predictors of peritonitis risk. Patients without a valid postcode were excluded, although this group only accounted for 1% of all PD patients. Distance from PD unit was based on the patient’s residence at the commencement of PD. Thus, it is possible that some patients moved from < to ≥ 100 km away from the PD unit or vice versa during their PD career, thereby leading to misclassification bias. In common with other Registries, ANZDATA is a voluntary Registry and there is no external audit of data accuracy, including the diagnosis of peritonitis. Consequently, the possibility of coding/classification bias cannot be excluded.

Our study represents the largest examination to date of the effect of living distantly from a PD unit on the risk, microbiology, treatment and clinical outcomes of PD-associated peritonitis. Living at least 100 km away from a PD unit was independently associated with a heightened risk of S. aureus peritonitis, modified approaches to peritonitis treatment (including less frequent hospitalisation, greater reliance on vancomycin-based regimens and a tendency to persist with antimicrobial agents in preference to catheter removal) and superior antimicrobial cure rates compared with patients living within 100 km of a PD unit. The heightened risk of S. aureus peritonitis and lower use of antifungal prophylaxis in remote living PD patients highlights the need to focus on implementation of evidence-based infection control strategies (such as staphylococcal decolonisation) in this patient group. Further research evaluating the effectiveness of different guideline implementation strategies on peritonitis prevention, particularly in remote-living PD patients, is warranted.