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

Abstract

The aim of the study was to determine whether distance between residence and peritoneal dialysis (PD) unit influenced peritonitis occurrence, microbiology, treatment and outcomes.
The study included all patients receiving PD between 1/10/2003 and 31/12/2008, using ANZDATA Registry data.
365 (6%) patients lived ≥100 km from their nearest PD unit (distant group), while 6183 (94%) lived <100 km (local group). Median time to first peritonitis in distant patients (1.34 years, 95% CI 1.07-1.61) was significantly shorter than in local patients (1.68 years, 95% CI 1.59-1.77, p = 0.001), whilst overall peritonitis rates were higher in distant patients (incidence rate ratio 1.32, 95% CI 1.20-1.46). Living ≥100 km away from a PD unit was independently associated with a higher risk of S. aureus peritonitis (adjusted odds ratio [OR] 1.64, 95% CI 1.09-2.47). Distant patients with first peritonitis episodes were less likely to be hospitalised (64% vs 73%, p = 0.008) and receive antifungal prophylaxis (4% vs 10%, p = 0.01), but more likely to receive vancomycin-based antibiotic regimens (52% vs 42%, p < 0.001). Using multivariable logistic regression analysis of peritonitis outcomes, distant patients were more likely to be cured with antibiotics alone (OR 1.55, 95% CI 1.03-2.24). All other outcomes were comparable between the two groups.
Living ≥100 km away from a PD unit was associated with increased risk of S. aureus peritonitis, modified approaches to peritonitis treatment and peritonitis outcomes that were comparable to, or better than patients living closer to a PD unit. Staphylococcal decolonisation should receive particular consideration in remote living patients.

Full text

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RESEARCH ARTICLEOpen Access
The effects of living distantly from peritoneal
dialysis units on peritonitis risk, microbiology,
treatment and outcomes: a multi-centre registry
study
Yeoungjee Cho1,2, Sunil V Badve1,2, Carmel M Hawley1,2, Stephen P McDonald1,3, Fiona G Brown1,4,
Neil Boudville M1,5, Kathryn J Wiggins1,6, Kym M Bannister1,7, Philip Clayton1,8and David W Johnson1,2,9*
Abstract
Background: The aim of the study was to determine whether distance between residence and peritoneal dialysis
(PD) unit influenced peritonitis occurrence, microbiology, treatment and outcomes.
Methods: The study included all patients receiving PD between 1/10/2003 and 31/12/2008, using ANZDATA
Registry data.
Results: 365 (6%) patients lived ≥100 km from their nearest PD unit (distant group), while 6183 (94%) lived
<100 km (local group). Median time to first peritonitis in distant patients (1.34 years, 95% CI 1.07-1.61) was
significantly shorter than in local patients (1.68 years, 95% CI 1.59-1.77, p=0.001), whilst overall peritonitis rates were
higher in distant patients (incidence rate ratio 1.32, 95% CI 1.20-1.46). Living ≥100 km away from a PD unit was
independently associated with a higher risk of S. aureus peritonitis (adjusted odds ratio [OR] 1.64, 95% CI 1.09-2.47).
Distant patients with first peritonitis episodes were less likely to be hospitalised (64% vs 73%, p=0.008) and receive
antifungal prophylaxis (4% vs 10%, p=0.01), but more likely to receive vancomycin-based antibiotic regimens (52%
vs 42%, p<0.001). Using multivariable logistic regression analysis of peritonitis outcomes, distant patients were
more likely to be cured with antibiotics alone (OR 1.55, 95% CI 1.03-2.24). All other outcomes were comparable
between the two groups.
Conclusions: Living ≥100 km away from a PD unit was associated with increased risk of S. aureus peritonitis,
modified approaches to peritonitis treatment and peritonitis outcomes that were comparable to, or better than
patients living closer to a PD unit. Staphylococcal decolonisation should receive particular consideration in remote
living patients.
Keywords: Antibiotics, Bacteria, Fungus, Microbiology, Peritoneal Dialysis, Peritonitis, Outcomes, Relapse,
Remoteness
* Correspondence: david_johnson@health.qld.gov.au
1Australia and New Zealand Dialysis and Transplant Registry, Adelaide,
Australia
2Department of Nephrology, University of Queensland at Princess Alexandra
Hospital, Brisbane, Australia
Full list of author information is available at the end of the article
© 2012 Cho et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
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Background
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 resi-
dence 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 in-
digenous patient dwellings have been proposed as reasons
for the observed outcomes. This study however defined re-
moteness based on the Accessibility and Remoteness Index
of Australia (ARIA) used by the Australian Bureau of Sta-
tistics rather than actual distance to the nearest PD unit.
Distance to the nearest PD unit may influence PD pa-
tient 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 treat-
ment 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, addres-
sing the impact of remote residence on PD outcomes, par-
ticularly 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.
Results
Population characteristics
A total of 6610 patients received PD in Australia during
the study period (1 October 2003 to 31 December 2008)
and were followed for 10470 patient-years (mean follow-up
1.58 years per patient). Their characteristics are depicted in
Table 1. In this group, 6213 episodes of peritonitis oc-
curred in 3128 (47%) patients (range 1 to 15 episodes per
patient). The overall rate of peritonitis was 0.59 episodes
per patient-year of treatment (equivalent to 20.2 patient-
months per episode).
The distance between patient residence and their nearest
PD unit was unable to be determined in 62 (1%) patients.
For the remaining patients, 365 (6%) lived ≥100 km from
their nearest PD unit (distant group), while 6183 (94%)
lived <100 km (local group). Their baseline characteristics
are shown in Table 1. Compared with local patients, distant
PD patients were significantly more likely to be younger,
Aboriginal and Torres Strait Islander peoples, have com-
menced dialysis at a lower level of estimated glomerular fil-
tration rate (eGFR), have chronic lung disease and diabetes
mellitus and not have a baseline peritoneal transport status
recorded.
Overall peritonitis rates in the distant and local groups
were 0.77 (95% CI 0.70-0.85) and 0.58 (95% CI 0.57-0.60)
episodes per patient-year, respectively (incidence rate ratio
1.32, 95% CI 1.20-1.46, p<0.001). When the analysis was
restricted to Caucasian patients, overall peritonitis rates in
the distant and local groups were 0.67 (95% CI 0.59-0.76)
and 0.59 (95% CI 0.57-0.61) episodes per patient-year, re-
spectively (incidence rate ratio 1.14, 95% CI 1.00-1.30,
p=0.05).
Peritonitis-free survival
Time to first peritonitis episode was significantly shorter in
distant patients (Figure 1). Median (95% confidence inter-
val) peritonitis-free survival rates were 1.34 (1.07-1.61)
years and 1.68 (1.59-1.77) years, respectively (log rank
score 10.6, p=0.001). Three-year peritonitis-free survival
rates were 19% and 31%, respectively. When the analysis
was restricted to Caucasians, the 3-year peritonitis-free
survival rates were 24% and 31%, respectively.
Using multivariable Cox proportional hazards model
analysis, living at least 100 km away from a PD unit was
not significantly, independently associated with time to
first peritonitis episode (adjusted hazard ratio [HR] 1.11,
95%CI0.94-1.31). The
increased peritonitis hazard were older age, Aboriginal and
Torres Strait Islander racial origin, Maori and Pacific Is-
lander racial origin, higher BMI and missing baseline peri-
toneal transport status. Receiving PD in a small-medium
centre (second smallest quartile) was associated with a
lower hazard of peritonitis than in the largest quartile.
independentpredictorsof
Microbiology of first peritonitis episodes
The micro-organisms isolated from dialysate cultures dur-
ing first episodes of peritonitis in distant and local PD
patients during the study period are summarised in Table 2.
Compared with local patients, distant patients were signifi-
cantly more likely to have Gram positive peritonitis due to
Staphylococcus aureus and Corynebacteria and less likely
to have non-Pseudomonas Gram negative peritonitis.
Methicillin-sensitive S. aureus accounted for 14% of S. aureus
isolates in distant patients and 21% of isolates in local
patients (p=0.5). Using multivariable logistic regression,
living at least 100 km away from the nearest PD unit was
significantly and independently associated with higher odds
of S. aureus peritonitis (adjusted odds ratio [OR] 1.64, 95%
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Table 1 Characteristics of Australian PD patients living within or greater than 100 km away from their nearest PD unit
during the study period 2003–2008
Characteristic
≥100 km from PD Unit (n=365)
<100 km from PD Unit (n=6183)P value
Age (years)56.9±16.8 59.1±16.90.02
Women 197 (54%) 3444 (56%)0.5
Racial origin
<0.001
Caucasian229 (63%) 4728 (76%)
ATSI 130 (36%) 391 (6%)
MPI 2 (1%) 157 (3%)
Asian 3 (1%) 628 (10%)
Other
BMI (kg/m2)
eGFR at dialysis start (mL/min/1.73 m2)
1 (0%) 279 (5%)
26.4±5.4 26.0±5.40.2
6.7±3.2 7.4±4.10.004
Late referral105 (29%) 1396 (23%)0.006
ESRD Cause0.08
Chronic glomerulonephritis103 (28%)1697 (27%)
Diabetic nephropathy 130 (36%)1806 (29%)
Renovascular disease 50 (14%)836 (14%)
Polycystic kidneys17 (5%) 348 (6%)
Reflux nephropathy11 (3%) 250 (4%)
Other 37 (10%) 831 (13%)
Unknown17 (5%) 415 (7%)
Smoking status0.1
Current 55 (15%) 746 (12%)
Former 142 (39%) 2295 (37%)
Never 168 (46%)3142 (51%)
Chronic lung disease66 (18%) 847 (14%)0.02
Coronary artery disease14 (39%) 2196 (36%) 0.2
Peripheral vascular disease 96 (26%) 1411 (23%)0.1
Cerebrovascular disease 54 (15%) 836 (14%)0.5
Diabetes mellitus160 (44%) 2349 (38%)0.03
Peritoneal Transport Status0.001
High 40 (11%)610 (10%)
High average106 (29%)2230 (36%)
Low average70 (19%) 1369 (22%)
Low 14 (4%) 271 (4%)
Unknown/Not specified135 (37%)1703 (28%)
Centre size
<0.001
Small (<7 patients) 2 (1%)42 (1%)
Small-medium (7–42 patients)65 (18%) 358 (6%)
Medium-large (43–140 patients)62 (17%)1382 (22%)
Large (>140 patients)236 (65%)4401 (71%)
Abbreviations: ATSI, Aboriginal and Torres Strait Islander peoples; BMI, body mass index; eGFR, estimated glomerular filtration rate; MPI, Maori and Pacific Islander
peoples.
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CI 1.09-2.47) and a trend to lower odds of non-Pseudomonas
Gram negative peritonitis (OR 0.68, 95% CI 0.45-1.01,
p=0.06). Similar results were found when the results were
restricted to Caucasian patients (S. aureus peritonitis OR
1.60, 95% CI 0.96-2.67, p=0.07; non-Pseudomonas Gram
negative peritonitis OR 0.65, 95% CI 0.39-1.08, p=0.10).
Initial empiric antibiotic treatment of first
peritonitis episodes
The majority of patients with peritonitis were treated ini-
tially with either intraperitoneal vancomycin or cephazolin
in combination with gentamicin (Table 3). Compared with
local patients, distant patients were significantly more
Figure 1 Kaplan-Meier survival curve for peritonitis-free survival for all Australian patients receiving PD between 1 October 2003 and
31 December 2008, according to whether they lived ≥100 km (n=365) or <100 km (n=6183) from their nearest PD unit. The difference
between the 2 Groups was statistically significant (log rank score 10.6, p=0.001).
Table 2 Micro-organisms isolated from dialysate cultures during first episodes of peritonitis in Australian PD patients
during the period 2003–2008, according to patient proximity to their nearest PD unit
Micro-organism
≥100 km from PD Unit (n=193)
<100 km from PD Unit (n=2915)P value
Culture-negative 32 (17%)409 (14%)0.3
Gram positive110 (57%) 1555 (53%) 0.3
S. aureus
35 (18%) 353 (12%) 0.01
Coagulase-negative staphylococci 51 (26%) 734 (25%) 0.7
Streptococci19 (10%)261 (9%) 0.7
Enterococci8 (4%) 118 (4%) 0.9
Corynebacterium0 (0%) 58 (2%)0.05
Pseudomonas 10 (5%)155 (5%) 0.9
Non-Pseudomonas Gram-negative 33 (17%)730 (25%) 0.01
Fungal 6 (3%) 116 (4%)0.5
Mycobacterium0 (0%) 11 (0.4%) 0.4
Polymicrobial19 (10%) 362 (12%)0.3
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likely to be treated empirically with a vancomycin-based
regimen, instead of a cephalosporin-based regimen.
Vancomycin-based regimens were also more commonly
prescribed in Caucasian patients (51% vs 44%, p=0.05).
Antifungal chemoprophylaxis was also less commonly
co-prescribed in distant patients (4% vs 10%, respectively,
p=0.01), as was heparin (9% vs 23%, p<0.001). There was
no difference between the 2 groups with respect to admin-
istration of thrombolytic agents (0% vs 0.3%, p=0.4).
When the analysis was restricted to Caucasian patients,
distant patients were less likely to be co-prescribed antifun-
gal prophylaxis (1% vs 4%, p=0.009) or heparin (5% vs
10%, p=0.01).
Outcomes of first peritonitis episodes
Compared with local PD patients, distant patients were sig-
nificantly less likely to be hospitalised for peritonitis
(Table 4). Those distant patients requiring temporary
transfer to haemodialysis for peritonitis were significantly
more likely to remain on temporary haemodialysis for
longer periods of time. Otherwise, peritonitis outcomes be-
tween the 2 groups were comparable with respect to cure
with antibiotics alone, relapse, catheter removal, perman-
ent haemodialysis transfer and death.
Using multivariable logistic regression analysis, living at
least 100 km away from the nearest PD unit was independ-
ently predictive of a higher rate of cure with antibiotics
alone (OR 1.55, 95% CI 1.03-2.24) and trends to lower
rates of catheter removal (OR 0.67, 95% CI 0.43-1.04,
p=0.07) and permanent haemodialysis transfer (OR 0.66,
95% CI 0.40-1.07, p=0.09). Distance from PD unit was not
associated with temporary haemodialysis transfer. The
number of events for death and relapse were too small to
permit adequate statistical analysis. When the analysis was
restricted to Caucasian patients, living at least 100 km
away from the nearest PD unit was not independently pre-
dictive of cure with antibiotics alone (OR 1.09, 95% CI
0.65-1.83), catheter removal (OR 0.95, 95% CI 0.54-1.66)
or permanent haemodialysis transfer (OR 0.86, 95% CI
0.47-1.57).
Discussion
The present study represents the largest examination to
date of the effect of distance from PD unit on the fre-
quency and clinical outcomes of PD-associated peritonitis.
Distant group patients were younger, more likely of indi-
genous 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 in-
dependently associated with a higher risk of S. aureus peri-
tonitis. 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 peri-
tonitis episodes in indigenous non-metropolitan patients
have been previously reported [14,16]. However, these
investigations defined remoteness based on the Accessibil-
ity 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 be-
tween 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
Table 3 Initial empiric antibiotic combinations administered to treat first episodes of peritonitis in Australian PD
patients during the period 2003–2007, according to patient proximity to their nearest PD unit. The differences
between the groups were statistically significant (p<0.001)
Antibiotic combination
1stgeneration cephalosporin+aminoglycoside
1stgeneration cephalosporin+3rd/4thgeneration cephalosporin
First-generation cephalosporin+other Gram-negative antibiotica
≥100 km from PD Unit (n=193)
<100 km from PD Unit (n=2915)
38 (20%) 1065 (37%)
35 (18%)452 (16%)
4 (2%) 29 (1%)
Vancomycin+aminoglycoside
Vancomycin+3rd/4thgeneration cephalosporin
Vancomycin+other Gram-negative antibiotica
Other Gram-positive antibioticb+aminoglycoside
Other Gram-positive antibioticb+3rd/4thgeneration cephalosporin
Other Gram-positive antibioticb+Other Gram-negative antibiotica
65 (34%) 974 (33%)
10 (5%)55 (2%)
25 (13%)213 (7%)
5 (3%)60 (2%)
1 (11%) 9 (0%)
10 (5%)58 (2%)
aOther Gram-negative antibiotics include (in decreasing order of frequency): ciprofloxacin, co-trimoxazole, metronidazole, erythromycin, aztreonam and fleroxacin.
bOther Gram-positive antibiotics include (in decreasing order of frequency): flucloxacillin, ampicillin, dicloxacillin, teicoplanin, amoxicillin and erythromycin.
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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 staphylococ-
cal decolonisation procedures in this group. Chronic car-
riage 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) demon-
strated 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 con-
ceivable 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 pub-
lished prospective survey of contemporary infection
prophylaxis practice in Australia and New Zealand PD
units demonstrated poor adherence to national and inter-
national 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 un-
known 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 hos-
pitalisation of remote patients (probably reflecting logistic
considerations) and the convenience of a less frequent dos-
ing requirement for vancomycin, which was more suited
to outpatienttreatment.
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 epi-
sodes in patients living at least 100 km away from the near-
est PD unit were comparable with those of patients
residing closer to nephrologic care. When adjustments
were made for differences in baseline characteristics (in-
cluding an over-representation of Aboriginal and Torres
Clinical outcomeswith
Table 4 Clinical outcomes of first episodes of peritonitis in Australian PD patients during the period 2003–2008,
according to patient proximity to their nearest PD unit
Outcome
≥100 km from PD Unit (n=193)
<100 km from PD Unit (n=2915)P value
Cure with antibiotics161 (83%)2283 (78%) 0.1
Relapse 4 (2%)40 (1%)0.4
Hospitalisation
Number (%)123 (64%)2115 (73%) 0.008
Duration6 [3-12] 6 [3-11]0.8
Catheter removal
Number (%)28 (15%) 538 (18%)0.2
Time to occurrence7 [2–13.75]6 [3-12] 0.6
Temporary haemodialysis
Number (%) 7 (4%)96 (3%) 0.8
Time to occurrence5 [2-8] 6.5 [3.25-10]0.4
Duration 125[88–145] 63.5 [20–94.25]0.007
Permanent haemodialysis
Number (%)22 (11%) 452 (16%) 0.1
Time to occurrence7.5 [2.75-20.25] 7 [4–12.75]0.8
Death
Number (%) 2 (1.0%)83 (1.8%) 0.4
Time to death -*15.5 [1.25-31.25] 0.4
* Unable to provide median [interquartile range] due to occurrence of only 2 deaths in this group.
Results are expressed as number (%) or median days [25th- 75thpercentile].
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Strait Islanders in remote living patients), distant patients
achieved higher cures rates with antimicrobial agents alone
and lower rates of catheter removal or permanent haemo-
dialysis transfer. These findings may reflect a stronger in-
centive 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 pub-
lished 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 conceiv-
able 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 re-
mote living patients. It is also possible that other factors
may have contributed to an apparent disparity in the find-
ings 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 Aborigi-
nal [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 condi-
tions 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 re-
ceiving 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 peri-
tonitis 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 lim-
itations, which included limited depth of data collection.
ANZDATA does not collect important information, such
as the presence of concomitant exit site and tunnel infec-
tions, antimicrobial susceptibilities of isolated micro-
organisms, patient compliance, socio-economic status, in-
dividualunitmanagement
approaches to staphylococcal decolonisation), duration of
cloudy dialysate, laboratory values (such as C-reactive pro-
tein and dialysate white cell counts), severity of comorbid-
ities, PD modality (ambulatory or continuous ambulatory
PD) at time of peritonitis, disconnect systems used, pre-
scribed PD dialysate (especially icodextrin), antibiotic
dosages or routes of antibiotic administration, peritoneal
dialysate culture methodology, previous antibiotic expos-
ure for any indication, or local availability of health services
in different remote regions (eg nephrologist outreach, pri-
mary 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 num-
ber of patients in the distant group (n=193) may have
reduced the power of the study to identify other independ-
ent 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, in-
cluding the diagnosis of peritonitis. Consequently, the pos-
sibility of coding/classification bias cannot be excluded.
protocols(includingthe
Conclusion
Our study represents the largest examination to date of the
effect of living distantly from a PD unit on the risk, micro-
biology, 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. aur-
eus peritonitis, modified approaches to peritonitis treat-
ment (including less frequent hospitalisation, greater
reliance on vancomycin-based regimens and a tendency to
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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 heigh-
tened risk of S. aureus peritonitis and lower use of antifun-
gal prophylaxis in remote living PD patients highlights the
need to focus on implementation of evidence-based infec-
tion control strategies (such as staphylococcal decolonisa-
tion) in this patient group. Further research evaluating the
effectiveness of different guideline implementation strat-
egies on peritonitis prevention, particularly in remote-
living PD patients, is warranted.
Methods
Study population
The study included all Australian adult patients from the
ANZDATA Registry who were receiving PD between 1st
October 2003 and 31stDecember 2008. Collection and
analysis of ANZDATA Registry data was approved by the
Princess Alexandra Hospital Human Research Ethics Com-
mittee. Permission to analyse the data was also granted by
the ANZDATA Registry Executive. The data collected
included demographic data, cause of primary renal disease,
co-morbidities at the start of dialysis, smoking status, body
mass index (BMI), late referral (defined as commencement
of dialysis within 3 months of referral to a nephrologist),
microbiology of peritonitis episodes (up to three organisms
for polymicrobial episodes) and the initial and subsequent
antibiotic treatment regimens. Centre size was categorised
according to quartiles of the numbers of patients cared for
by individual units over the duration of the study: small
(<7 patients), small-medium (7–42 patients), medium-
large (43 – 140 patients) and large (>140 patients).
Patients were analysed according to whether their resi-
dence was located ≥100 km (distant) or <100 km (local)
from their nearest PD unit. Distance between patient resi-
dence (based on postcode) and peritoneal dialysis unit was
determined using Google maps (www.maps.google.com.
au). This distance represented travelling distance, rather
than straight line distance. The distance of 100 km was
chosen a priori because this is the minimum distance for
which most state governments of Australia provide
patient-assisted transport subsidy schemes to facilitate
improved access of remote living patients to specialised
medical care.
Peritonitis was defined as clinical features of peritonitis
(abdominal pain or cloudy dialysate) and dialysate
leukocytosis (white blood cell count>100/μL with>50%
neutrophils). Peritonitis rates were calculated according to
the standardised recommendations made by the Inter-
national Society of Peritoneal Dialysis (ISPD) [25,26].
The outcomes examined
peritonitis-free survival, microbiology, antimicrobial ther-
apy, cure, relapse, peritonitis-associated hospitalization,
catheter removal, temporary haemodialysis transfer (in
wereperitonitis rate,
which patients subsequently resumed PD), permanent
haemodialysis transfer and patient death. A peritonitis epi-
sode was considered “cured” by antibiotics alone if the pa-
tient was symptom free, the PD effluent was clear and the
episode was not complicated by relapse, catheter removal
or death. Peritonitis-related death was recorded if the
patient’s death was directly attributable to peritonitis in the
clinical opinion of the treating nephrologist. In view of the
complexities associated with analysis of multiple events
within individuals where the assumption of independence
of observations is not appropriate, only the first episodes of
peritonitis from each individual were included when ana-
lysing all outcomes, except peritonitis rates.
Statistical analysis
Results were expressed as frequencies and percentages,
mean±standard deviation or median [25th- 75thpercent-
ile], as appropriate. Differences between groups were ana-
lysed by chi-square test for categorical data, unpaired t-test
for continuous normally distributed data and Mann–Whit-
ney test for continuous non-normally distributed data.
Peritonitis rates were compared by Poisson regression ana-
lysis. Peritonitis-free survival was determined by Kaplan-
Meier survival analysis and by multivariable, Cox propor-
tional hazards model analysis using backward stepwise
elimination. The independent predictors of the clinical out-
comes of peritonitis were determined by multivariable lo-
gistic regression. Distance from PD unit, age, gender, racial
origin, BMI, eGFR at dialysis start, late referral within
3 months of dialysis commencement, ESRD cause, smok-
ing status, comorbidities, peritoneal transport status, cli-
matic region, centre size, isolated organism, initial empiric
antibiotic regimen and isolated micro-organisms were
included in the model as covariates. Assumptions for the
Poisson regression, logistic regression and Cox propor-
tional hazards models were verified. First-order interaction
terms between the significant covariates were examined,
where appropriate. Data were analysed using the software
package PASW Statistics for Windows release 18.0 (SPSS
Inc., North Sydney, Australia). P values less than 0.05 were
considered statistically significant.
Abbreviations
ANZDATA: Australian and New Zealand Dialysis and Transplant Registry;
ARIA: Accessibility and Remoteness Index of Australia; ATSI: Aboriginal or
Torres Strait Islander; BMI: Body mass index; eGFR: Estimated glomerular
filtration rate; ESRD: End-stage renal disease; HR: Adjusted hazard ratio;
ISPD: International Society of Peritoneal Dialysis; MPI: Maori or Pacific Islander;
NPGN: Non-pseudomonas Gram-negative organism; OR: Adjusted odds ratio;
PD: Peritoneal dialysis.
Competing interests
Professor David Johnson is a consultant for Baxter Healthcare Pty Ltd and
has previously received research funds from this company. He has also
received speakers’ honoraria and research grants from Fresenius Medical
Care and has previously been a consultant to Gambro. He is supported by a
Queensland Government Health Research Fellowship. Dr Kym Bannister is a
consultant for Baxter Healthcare Pty Ltd. Dr Fiona Brown is a consultant for
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Baxter and Fresenius and has received travel grants from Amgen and Roche.
Dr Stephen McDonald has received speaking honoraria from AMGEN
Australia, Fresenius Australia and Solvay Pharmaceuticals and travel grants
from AMGEN Australia, Genzyme Australia and Jansen-Cilag. Associate
Professor Neil Boudville has previously received research funds from Roche,
travel grants from Roche, Amgen and Jansen Cilag, and speaking honoraria
from Roche. The remaining authors have no competing financial interests to
declare.
Acknowledgements
The authors gratefully acknowledge the substantial contributions of the
entire Australia and New Zealand nephrology community (physicians,
surgeons, database managers, nurses, renal operators, and patients) in
providing information for and maintaining the ANZDATA Registry database.
Author details
1Australia and New Zealand Dialysis and Transplant Registry, Adelaide,
Australia.2Department of Nephrology, University of Queensland at Princess
Alexandra Hospital, Brisbane, Australia.3Department of Nephrology &
Transplantation Services, University of Adelaide at the Queen Elizabeth
Hospital, Adelaide, Australia.4Department of Nephrology, Monash Medical
Center, Melbourne, Australia.5School of Medicine and Pharmacology,
University of Western Australia, Perth, Australia.6Department of Renal
Medicine,, Royal Melbourne Hospital,, Melbourne, Australia.7Department of
Nephrology, Royal Adelaide Hospital, Adelaide, Australia.8Department of
Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia.9Department
of Nephrology, Level 2, ARTS Building, Princess Alexandra Hospital, Ipswich
Road, Woolloongabba, Brisbane, Qld 4102, AUSTRALIA.
Authors’ contributions
YC and DJ conceived of the study; participated in the study design and the
analysis and interpretation of the results; helped to draft the manuscript. SB,
CH, SM, FB, NB, KW, KB and PC participated in the study design and the
analysis and interpretation of the results. All authors read and approved the
final manuscript.
Received: 27 January 2012 Accepted: 15 June 2012
Published: 15 June 2012
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doi:10.1186/1471-2369-13-41
Cite this article as: Cho et al.: The effects of living distantly from
peritoneal dialysis units on peritonitis risk, microbiology, treatment and
outcomes: a multi-centre registry study. BMC Nephrology 2012 13:41.
Cho et al. BMC Nephrology 2012, 13:41
http://www.biomedcentral.com/1471-2369/13/41
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