266
This effort was initiated to assess the efficacy and
validity of the pediatric guidelines and to enhance
existing knowledge regarding the global variability of bacteriology and antibiotic susceptibilities
associated with peritonitis in children on PD [7,
8]. Data from that study, and the subsequent
IPPN/IPDN Registry, informed the development
of updated clinical practice guidelines for the
prevention and treatment of PD-related infections in children and adolescents on PD, which
were published in 2012 [9]. Those guidelines,
and the studies used to develop them, form the
basis for much of this chapter.
In 2011, the Standardizing Care to Improve
Outcomes in Pediatric End-Stage Renal Disease
(SCOPE) collaborative, a quality transformation
network of nearly 50 pediatric dialysis centers in
the United States, was launched with the goal of
reducing PD-related infections by increasing
implementation of standardized PD catheter care
practices [10]. The care practices, or bundles,
included in the SCOPE collaborative were largely
derived from the ISPD pediatric guidelines [9,
10]. Data from the SCOPE collaborative, which
has demonstrated a significant reduction in peritonitis rates among participating centers, support
much of the information included in this chapter’s discussion of risk factors and infection prevention [11, 12].
Incidence of PD-Related Infections
Peritonitis rates among children on chronic PD
have improved substantially over the past few
decades, likely related to technical improvements
in connectology, and increased emphasis on
training and patient education [13–16]. According
to the NAPRTCS 2011 Dialysis Report, the annualized peritonitis rate among children enrolled in
that registry decreased from 0.79 episodes per
patient year in children who initiated PD between
1992 and 1996 to 0.44 in those children who initiated PD between 2007 and 2010 [1]. Among
children participating in the IPPN registry
between 2007 and 2018, the annualized rate of
A. M. Neu et al.
peritonitis was 0.44 [17]. Of note, IPPN data did
not demonstrate any variation in infection rates
between high- and low-resourced regions [8, 17].
Despite these improvements, these peritonitis
rates still exceed the rate of 0.17 episodes per
patient year reported among 130 Japanese children maintained on chronic PD between 1999
and 2003 [18].
Rates of PD catheter-related infections are
less often cited, but data from the IPPN revealed
an exit-site/tunnel infection rate of 0.13 infections per patient year among patients enrolled in
that registry between 2011 and 2014 [19]. The
exit-site/tunnel infection rate among SCOPE participating centers was 0.25 episodes per catheter
year during the same period (2011–2014) [20].
To guide quality improvement efforts aimed at
reducing PD-related infections, both pediatric
and adult ISPD peritonitis guidelines suggest that
centers monitor their PD-related infection rates
on a regular basis [9, 21, 22]. Organism-specific
rates should be monitored as well, as the various
organisms may direct improvement efforts to
specific aspects of care [9, 21, 22]. For example,
an increase in peritonitis rates with skin flora may
prompt efforts to increase recognition and appropriate treatment for touch contamination [9, 21–
23]. In addition, the antibiotic susceptibilities of
the organisms should be monitored, which will
allow the development of center-specific empiric
antibiotic regimens [9, 21–23]. Population-based
peritonitis rates can be misleading, because peritonitis risk is not evenly distributed across the PD
population – some patients have few, if any,
infections while others experience many. The
4248 episodes of peritonitis reported to the
NAPRTCS registry between 1992 and 2001
occurred in fewer than half of the 4430 PD
patients enrolled during this period, with 877
patients experiencing only 1 peritonitis episode,
432 experiencing 2 infections, 482 experiencing
3–7 infections, and 53 patients with 8 or more
peritonitis episodes [1]. These data emphasize
the potential value of expressing the average risk
of peritonitis for a dialysis unit as the median of
patient-specific peritonitis rates [24].
16 Infectious Complications of Peritoneal Dialysis in Children
267
Microbiology of PD-Related
Infections
negative and 4% by fungal organisms [19]. The
most common causative organisms were
coagulase-negative Staphylococci (24.7%),
Peritonitis
Staphylococcus aureus (S. aureus) (22.2%),
Escherichia coli (7.7%), Streptococci (6.9%),
The majority of peritonitis episodes in children Pseudomonas species (6.3%), and Enterococci
on PD are caused by bacteria, and historically the (5.5%) [19]. There was, however, significant
percentage of infections caused by fungi has been regional variability in the distribution of organless than 5% [25]. This trend was confirmed by isms with gram-positive infections predominant
data from the IPPR, where only 10 of 501 (2%) in Europe, coagulase-negative Staphylococci
episodes of peritonitis were due to fungi [26]. Of most common in Eastern Europe, S. aureus prethe remaining episodes, gram-positive organisms dominant in Western Europe, and Enterococci in
were cultured in 44% and gram-negative in 25%, Turkey (Fig. 16.1) [8]. Conversely, gram-negative
while 31% of peritonitis episodes were associ- organisms were predominant in Argentina and
ated with a negative bacterial culture [26]. These the United States, where they accounted for 70%
distributions were confirmed by data from the and 46% of culture-positive infections, respecIPPN/IPDN, which revealed that among the 1456 tively [8]. Pseudomonas species were the most
peritonitis episodes reported to that registry common gram-negative organism cultured in the
between 2007 and 2014, the culture-negative rate United States, while other gram-negative organwas 33% [19]. Of the culture-positive cases, 63% isms were more common in Argentina [8]. S.
were caused by gram-positive, 33% by gram- aureus and Staphylococcus epidermidis (S. epi)
70
60
50
%
40
30
20
Gram-positive
10
Gram-negative
Culture-negative
Fungal
co
ex
i
M
ke
y
As
i
a
Tu
r
rn
te
W
es
Ea
st
er
n
Eu
Eu
ro
pe
ro
p
e
U
SA
Ar
ge
nt
in
a
0
Data:
Fungal
Culturenegative
Gram-negative
Gram-positive
Argentina
USA
Western
Europe
2.45
23.31
Asia
Turkey
Mexico
3.61
10.84
Eastern
Europe
1.92
19.23
0
14.81
0
36
1.23
44.37
0
66
59.3
25.9
40.96
44
23.1
55.8
18.41
55.8
36
28.6
20.25
37.4
11.1
22.2
Fig. 16.1 Distribution of causative organisms according to regions among 501 episodes peritonitis reported by the
IPPR. (Adapted from Ref. [8])
A. M. Neu et al.
268
remain the most frequently isolated organisms in
a more recent analysis of more than 2000 episodes of peritonitis reported to the IPPN, with
culture-negative peritonitis most common in
Turkey and Latin America [17]. This analysis
also noted significant regional variation in antibiotic susceptibility for aminoglycosides and methicillin [17]. The SCOPE collaborative reported
that among 389 episodes of peritonitis for which
culture results were available, 37.8% were due to
gram-positive organisms and 19.5% to gram-
negative organisms [12]. Thirty (7.7%) fungal
infections were reported, while 10.3% of cultures
were polymicrobial, and 24.7% of the cultures
were negative [12]. S. epi. was the most common
gram-positive organism, while Pseudomonas
species were the most common gram-negative
organisms identified [12]. It has been proposed
that this geographic variability in causative
organisms is likely multifactorial in origin and
factors may include environmental influences,
such as climate and humidity, and variability in
PD practices, including exit-site care and the routine use of topical antibiotic prophylaxis [27].
The IPPR discovered not only a wide regional
variability in causative organisms but also in the
rate of culture-negative peritonitis in their participating sites, representing from 11% to 67% of all
center episodes [8]. A survey of the laboratory
procedures among the participating centers did
not reveal systematic differences in culture technique to explain this variability, but it was hypothesized that issues such as incubation of
insufficient effluent volumes, long sample transport times in rural areas, and extreme ambient
temperatures may have adversely affected culture
results [8]. Similarly, the culture-negative peritonitis rate among SCOPE centers is quite high, at
24.7% [12]. A recent analysis of the data showed
a significant center-to-center variability in
culture-
negative rates, ranging from 7.1% to
61.1%, as well as a significant variability in the
culture techniques among the centers [28]. Since
culture technique may influence the likelihood of
isolating an organism from peritoneal effluent,
the SCOPE collaborative has developed a standardized protocol for obtaining a culture from
peritoneal dialysis effluent and processing the
sample, based on the procedure recommended in
the ISPD guidelines. Compliance with this culture “bundle” and the associated rates of culturenegative peritonitis will be tracked following
implementation of this bundle [9].
As mentioned above, fungi account for a
minority of peritonitis episodes and represent just
2% of episodes in the IPPR report and 4% among
episodes reported to IPPN, with a slightly higher
rate seen in the SCOPE collaborative [12, 19,
26]. Candida species are the most common fungal organisms implicated. In the largest pediatric
report addressing this infection, Candida species
accounted for 79% of all fungal infections, with
nearly 24% due to Candida albicans and more
than 26% secondary to Candida parapsilosis
[29–31].
PD Catheter-Related Infections
PD catheter exit-site and tunnel infections may
be caused by many organisms, including normal
skin flora such as Corynebacteria [24, 32]. S.
aureus infections are the most common, with or
without S. aureus nasal carriage [20, 33, 34]. PD
catheter-related infections due to gram-negative
organisms, especially Pseudomonas species, are
increasingly common [8, 35].
Risk Factors and Prevention
Analyses of data from large pediatric dialysis
registries have revealed associations between
many factors and the risk for PD-related infections, primarily peritonitis, in children on
PD. Recognition of these risk factors is important, as they may prompt modification of care
practices, which, in turn, may lower infection
rates.
Patient Age
Data from the NAPRTCS has long revealed that
peritonitis rates increase with decreasing age at
dialysis initiation [1]. Data from the IPPR
16 Infectious Complications of Peritoneal Dialysis in Children
c onfirmed a statistical association between young
age and gram-negative peritonitis, and patients
2 years and under at dialysis initiation had the
highest rates of peritonitis among children
enrolled in the SCOPE collaborative [12, 36, 37].
An additional analysis of data from 156 infants
enrolled in SCOPE, including neonates on
chronic PD who had not yet been discharged
from the hospital, revealed a peritonitis rate of
1.73 episodes per patient year, among those
infants who remained hospitalized, and an overall annualized rate of 0.76 [38]. Multivariable
regression models demonstrated that nephrectomy prior to or at the time of PD catheter placement and gastrostomy tube placement after PD
catheter placement were associated with a significantly increased risk of peritonitis in this
group of infants [38]. It seems intuitive that the
relatively close proximity of the PD catheter to
the diaper region or urinary or gastrointestinal
ostomy sites in a small infant would increase the
risk for bacterial contamination and subsequent
infection, in fact, some centers have reported
improvement in the infection rates of such
patients, by placing the PD catheter exit-site in a
presternal location [39, 40].
269
IPPR, a single-cuff catheter and a downward orientation of the exit-site were independent risk
factors for relapsing peritonitis [43]. Data from
the IPPR also revealed a nearly 13 times increased
risk for gram-negative peritonitis associated with
a single-cuff catheter [36]. In the recent IPPN
analysis, an upward pointing exit-site continued
to be associated with an increased risk for peritonitis (OR 1.26, p < 0.001) [17]. A univariate analysis of catheter characteristics in patients with
and without a history of peritonitis in the SCOPE
collaborative revealed no difference in the percentage of patients with a swan-neck tunnel or
with two subcutaneous cuffs, but subgroup analysis by organism was not performed [12]. Upward
orientation of the exit-site was associated with a
higher risk for peritonitis in multivariable analysis [12]. Current guidelines recommend the use
of a double-cuff catheter with a downward- or
lateral-oriented exit-site [9].
Other efforts to minimize the risk for peritonitis at the time of catheter placement include the
provision of antibiotics prior to surgical incision,
in order to reduce the risk for wound infection
and peritonitis in the postoperative period [9, 44,
45]. Although vancomycin may be slightly more
effective than a first-generation cephalosporin in
the prevention of postoperative peritonitis, the
PD Catheter Design, Insertion,
use of the latter is recommended, because of conand Postoperative Exit-Site Care
cern for the generation of vancomycin resistance
as a result of repeated usage [9, 21, 45, 46]. The
Early data from the NAPRTCS suggested that a ultimate choice of antibiotic for perioperative
catheter with two subcutaneous cuffs rather than prophylaxis should be influenced by the PD
one; a swan-neck tunnel; and a downward or lat- unit’s antibiotic susceptibility patterns [9, 21].
eral directed exit-site orientation rather than
Placement of the PD catheter using a laparoupward, were associated with lower peritonitis scopic technique, rather than an open surgical
rates and longer time to the first peritonitis epi- procedure, has become increasingly common in
sode [41]. A subsequent analysis revealed a sig- pediatric centers, and among patients enrolled in
nificant increase in the use of this catheter the SCOPE collaborative more than 60% of cathconfiguration among NAPRTCS centers, and, eters are placed using this technique [47].
associated with this trend, tunnel type (swan- Retrospective single-center studies have not
neck versus straight), number of cuffs, and exit- demonstrated a difference in infection rates
site orientation were no longer associated with between catheters placed laparoscopically versus
the risk for peritonitis in patients who initiated an open surgical insertion [48, 49]. More recently,
PD between 1997 and 2000, compared to those the analysis of data from the SCOPE collaborawho initiated dialysis between 1992 and 1996 tive showed no difference in the percentage of
[42]. In a multivariate analysis performed on 490 patients undergoing laparoscopic versus open PD
non-fungal episodes of peritonitis reported by the catheter placement among those patients with
A. M. Neu et al.
270
and without early peritonitis, defined as infection
within 60 days of catheter placement [47]. Once
the catheter is inserted, sutures should be avoided
at the catheter exit-site, as they may increase the
risk of bacterial colonization and subsequent
infection [50, 51].
In the immediate postoperative period, PD
catheter and exit-site care are aimed at optimizing healing and minimizing bacterial colonization [52]. Current guidelines suggest that the
sterile dressing placed in the operating room following PD catheter placement remain in place for
at least 1 week. Subsequent dressing changes
should be performed by a trained staff, using
aseptic technique, and should occur no more frequently than weekly until the exit-site is healed
[9, 53]. More frequent dressing changes should
be performed only if the dressing becomes loose,
damp, or soiled [9]. The catheter should be
immobilized to optimize healing and minimize
trauma [54]. Immobilization with tape or a dressing is usually sufficient, although commercially
available immobilization devices may also be
used [9]. It is generally recommended that initiation of dialysis be delayed for at least 2 weeks
following catheter placement to minimize risk of
leak at the peritoneal insertion site, although exit-
site healing may take as long as 6 weeks. The
care practices described here, and included in the
most current ISPD guidelines for children, are
derived primarily from the work done by Prowant
and Twardowski over 20 years ago [52–54].
The care practices monitored by the SCOPE
collaborative include a PD catheter insertion bundle [10]. The elements of this bundle, which
address PD catheter insertion and the immediate
postoperative care, were derived largely from the
ISPD guidelines [9, 10]. The required care elements include the provision of an intravenous
antibiotic prior to skin incision at the time of PD
catheter placement, avoidance of sutures at the
exit-site, no dressing change for at least 7 days
following catheter placement unless soiled, loose
or damp, sterile dressing changes performed by a
healthcare professional until the exit-site is
healed, and no use of the catheter for dialysis
until at least 14 days following placement [9, 10].
In the first 3 years of the collaborative, compli-
ance with the majority of these care practices has
been high (80–90%), highlighting the capacity to
incorporate these practices into clinical care [11].
The one exception is the requirement to avoid the
use of the catheter for dialysis within the first 14
postoperative days, for which compliance across
the collaborative has been between 50% and
60%, largely as a result of patients requiring
prompt initiation of dialysis [11]. Whereas an
early analysis of SCOPE data failed to detect an
association between compliance with the PD
catheter insertion bundle and risk for peritonitis
at the patient level, a more recent analysis, which
focused on peritonitis episodes in the first 60 days
following catheter insertion, revealed a significant association between the risk for early peritonitis and initiation of dialysis within 14 days of
catheter placement [47]. While there was no
association found between compliance with the
other bundle elements and the risk for early peritonitis, the high rate of compliance with these
other care practices across the collaborative may
have limited the ability to detect an association
between compliance and infection risk [47].
Training
Because PD is a home dialysis therapy, appropriate training of patients and caregivers is essential
to minimize the risk for peritonitis. Unfortunately,
there are no randomized controlled trials to evaluate the relationship between various training
elements or the training process itself and patient
outcomes [55–57]. There are, however, several
observational studies, which have sought associations between variations in timing of training,
training content, training duration, nurse-to-
patient ratios, and experience of the trainer and
risk for peritonitis in both adult and pediatric settings [55–59]. In recent analyses of data from
Brazil, shorter training time (<15 h), training in
the 10 days after catheter insertion, and small
center size were associated with increased risk
for peritonitis [60]. In a survey of pediatric dialysis units, center size (≥15 patients) and longer
training time dedicated to theory and practical/
technical skills were associated with lower
16 Infectious Complications of Peritoneal Dialysis in Children
p eritonitis rates [58]. In agreement with the suggestions of the ISPD Nursing Liaison Committee,
current pediatric guidelines suggest that PD
training should use a formalized teaching program that has clear objectives and criteria, with
the incorporation of adult learning principles [9,
55]. The training should be performed by an
experienced PD nurse with pediatric training and
should include core topics, including those
related to infection prevention such as hand
hygiene, aseptic technique, exit-site care, and
appropriate treatment for contamination [9, 55].
It is suggested that PD training should include no
more than one patient/family simultaneously [9,
55]. More recently, the ISPD published a syllabus
for teaching PD to patients and caregivers, which
includes a checklist for PD assessment and
another for PD training [61]. It remains to be
determined if widespread use of this syllabus and
the associated tools leads to a decrease in the rate
of infection.
The SCOPE collaborative monitors compliance with a training bundle, the elements of
which were derived from the ISPD guidelines [9,
10]. The required elements include the following:
(1) training must be performed by a registered
nurse; (2) there should be only one patient/family
per training session; (3) all of the elements recommended by the ISPD guidelines for training
must be included in the training, and specific protocols for hand hygiene, aseptic technique, and
exit-site care must be taught; (4) verification of
competence at the end of training must be
assessed, using both a written and a demonstration test; and (5) a home visit must be performed
[9, 10, 55]. An analysis of the first 3 years of
SCOPE data revealed that compliance with most
of these bundle elements was high (90%) across
the collaborative, except for the requirement to
perform a home visit, which only occurred in
65–80% of cases as a result of various logistical
issues [11]. No association between compliance
with the overall training bundle and risk for peritonitis was demonstrated, either across the collaborative sites or when evaluated at the patient
level [12], possibly as a result of the relatively
high compliance with most bundle elements
(vide infra) [11, 12].
271
Current guidelines suggest periodic retraining
of patients/caregivers, particularly after a peritonitis episode [9, 55]. The Trial on Education and
Clinical outcomes for Home PD patients
(TEACH), a multicenter, open-labeled, randomized, controlled trial, compared PD-related infections in adult PD patients randomized to receive
home visits for retraining every 1–3 months over
a 24-month period compared to no retraining
[62]. Both groups received the same initial training and two home visits in the first 2 months after
starting PD [62]. The study failed to demonstrate
a significant difference in peritonitis rates
between the two groups, although a sub-analysis
demonstrated a significantly lower risk for the
first peritonitis episode in patients older than
60 years of age who received frequent home visits [62]. The SCOPE collaborative includes a
“follow-up” care bundle, which consists of a
review of key aspects of hand hygiene, exit-site
care, and aseptic technique at each monthly follow-up visit in the clinic [10]. Competency with
these procedures is also demonstrated by the
patient/caregiver, using both a concept and a
demonstration test, every 6 months [10]. Finally,
the follow-up bundle requires that the appearance
of the PD catheter exit-site be scored, using an
objective storing tool developed by the Mid-
European Pediatric Peritoneal Dialysis Study
Group, and that touch contaminations be treated
according to the ISPD guidelines (Table 16.1) [9,
10, 63]. Using a quality improvement methodology, SCOPE centers were able to demonstrate a
significant increase in compliance with this care
bundle over the first 3 years of the collaborative,
accompanied by a significant reduction in peritonitis rates, from a pre-launch mean monthly
peritonitis rate of 0.63 episodes per patient year
Table 16.1 Catheter exit-site scoring system [63]
Swelling
Crust
Redness
Pain on
pressure
Secretion
0 Points 1 Point
No
Exit only
(<0.5 cm)
No
<0.5 cm
No
<0.5 cm
No
Slight
2 Points
Including part of
or entire tunnel
>0.5 cm
>0.5 cm
Severe
No
Purulent
Serous