ISPD Guideline 2010
ISPD Guideline 2010
ISPD Guideline 2010
393423
doi:10.3747/pdi.2010.00049
ISPD GUIDELINES/RECOMMENDATIONS
Department of Medicine and Therapeutics,1 Prince of Wales Hospital, The Chinese University of Hong Kong,
Hong Kong; University of Pittsburgh School of Medicine,2 Pittsburgh, PA, USA; Faculdade de Enfermagem,
Nutrio e Fisioterapia,3 Pontifcia Universidade Catlica do Rio Grande do Sul, Brazil; Sanjay Gandhi
Postgraduate Institute of Medical Sciences,4 Lucknow, India; Department of Nephrology,5 Princess Alexandra
Hospital, and School of Medicine, University of Queensland, Brisbane, Australia; Department of Medical
Microbiology,6 Leiden University Medical Center, Leiden, The Netherlands; Centre for Kidney Diseases,7
Mount Elizabeth Medical Centre, Singapore; Section of Infectious Disease,8 Department of Internal Medicine,
University of Missouri-Columbia School of Medicine, Columbia, MO, USA; Pediatric Nephrology
Division,9 University Childrens Hospital, Heidelberg, Germany; Dianet Dialysis Centers,10
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
eritonitis remains a leading complication of peritoneal dialysis (PD). Around 18% of the infection-related
mortality in PD patients is the result of peritonitis. Although less than 4% of peritonitis episodes result in
death, peritonitis is a contributing factor to death in
16% of deaths on PD. In addition, severe and prolonged
peritonitis can lead to peritoneal membrane failure and
peritonitis is probably the most common cause of technique failure in PD. Peritonitis remains a major cause of
patients discontinuing PD and switching to hemodialysis. Therefore, the PD community continues to focus attention on prevention and treatment of PD-related
infections (19). Peritonitis treatment should aim for
rapid resolution of inflammation and preservation of
peritoneal membrane function.
Recommendations under the auspices of the International Society for Peritoneal Dialysis (ISPD) were first
published in 1983 and revised in 1989, 1993, 1996, 2000,
and 2005 (1013). The previous recommendations inThe authors are members of the ISPD Ad Hoc Advisory Committee on Peritoneal Dialysis Related Infections.
www.PDIConnect.com
doi:10.3747/pdi.2010.00049
393
Philip Kam-Tao Li,1 Cheuk Chun Szeto,1 Beth Piraino,2 Judith Bernardini,2 Ana E. Figueiredo,3
Amit Gupta,4 David W. Johnson,5 Ed J. Kuijper,6 Wai-Choong Lye,7
William Salzer,8 Franz Schaefer,9 and Dirk G. Struijk10
LI et al.
TABLE 1
Methods for Reporting Peritoneal Dialysis-Related Infections
(Peritonitis, Exit-Site Infections) (16)
1. As rates (calculated for all infections and each organism):
Months of peritoneal dialysis at risk, divided by number
of episodes, and expressed as interval in months between episodes
Number of infections by organism for a time period, divided by dialysis-years time at risk, and expressed as
episodes per year
2. As percentage of patients who are peritonitis free per period of time
3. As median peritonitis rate for the program (calculate peritonitis rate for each patient and then obtain the median of
these rates)
Relapsing peritonitis (see Table 6 for the definition) should
be counted as a single episode.
Although many of the general principles could be applied to pediatric patients, recommendations outlined
here focus on PD-related infections in adult patients.
Clinicians who take care of pediatric PD patients
should refer to other sources for detailed treatment regimens and dosages.
These recommendations are evidence based where
such evidence exists. The bibliography is not intended
to be comprehensive as there have been nearly 10 000
references to peritonitis in PD patients published since
1966. The Committee has chosen to include articles that
are more recently published (i.e., after the most recent
recommendation, published in 2005) and those considered key references. These recommendations are not
based solely on randomized controlled trials because
such studies in PD patients are limited. Where there is
no definitive evidence but the group feels there is sufficient experience to suggest a certain approach, this is
indicated as opinion based. The recommendations are
not meant to be implemented in every situation but are
recommendations only. Each center should examine its
own pattern of infection, causative organisms, and sensitivities and adapt the protocols as necessary for local
conditions.
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TABLE 2
250500 mg b.i.d.
500 mg b.i.d. to t.i.d. (41)
250 mg b.i.d. (29)
500 mg loading dose, then
250 mg b.i.d. or q.d. (30)
Dicloxacillin
500 mg q.i.d.
Erythromycin
500 mg q.i.d.
Flucloxacillin (or cloxacillin)
500 mg q.i.d.
Fluconazole
200 mg q.d. for 2 days,
then 100 mg q.d. (41)
Flucytosine
0.51 g/day titrated to response and serum trough
levels (2550 g/mL) (41)
Isoniazid
200300 mg q.d. (42)
Linezolid
400600 mg b.i.d. (41)
Metronidazole
400 mg t.i.d.
Moxifloxacin
400 mg daily
Ofloxacin
400 mg first day, then
200 mg q.d.
Pyrazinamide
2535 mg/kg 3 times per
week (31)
Rifampicin
450 mg q.d. for <50 kg;
600 mg q.d. for >50 kg
Trimethoprim/sulfamethoxazole 80/400 mg q.d.
b.i.d. = 2 times per day; q.d. = every day; t.i.d. = 3 times per
day; q.i.d. = 4 times daily.
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Exit-site and tunnel infections may be caused by a variety of micro-organisms. Although S. aureus and P. aeruginosa are responsible for the majority of infections,
other bacteria (diphtheroids, anaerobic organisms, nonfermenting bacteria, streptococci, nontuberculous mycobacteria, Legionella, yeasts, and fungi) can also be
involved. Empiric antibiotic therapy may be initiated
immediately. Alternatively, the healthcare team may decide to defer therapy until the results of the exit-site
culture can direct the choice of antibiotic. Microbiological examination should preferably include a combination of microscopy with aerobic and anaerobic culture.
The Gram stain of exit-site drainage and the microbiological culture findings can guide the initial therapy.
Cultures should be taken to the laboratory using appropriate transport materials also allowing anaerobic bacteria to survive. Oral antibiotic therapy has been shown
to be as effective as intraperitoneal (IP) antibiotic
therapy.
Empiric therapy should always cover S. aureus. If the
patient has a history of P. aeruginosa exit-site infections,
empiric therapy should be with an antibiotic that will
cover this organism. In some cases, intensified local care
or a local antibiotic cream may be felt to be sufficient in
the absence of purulence, tenderness, and edema.
Gram-positive organisms are treated with oral penicillinase-resistant (or broad spectrum) penicillin or a
first-generation cephalosporin, such as cephalexin. Dosing recommendations for frequently used oral antibiotics are shown in Table 2 (41). To prevent unnecessary
exposure to vancomycin and thus emergence of resistant organisms, vancomycin should be avoided in the
routine treatment of gram-positive exit-site and tunnel
infections but will be required for MRSA infections.
Clindamycin, doxycycline, and minocycline are sometimes useful for the treatment of community-acquired
MRSA and other organisms; these drugs do not require
dose adjustment for end-stage renal disease. In slowly
resolving or particularly severe S. aureus exit-site infections, rifampicin 600 mg daily may be added, although
this drug should be held in reserve in areas where tuber-
Amoxicillin
Cephalexin
Ciprofloxacin
Clarithromycin
LI et al.
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Peritoneal dialysis patients presenting with cloudy effluent should be presumed to have peritonitis. This is
confirmed by obtaining effluent cell count, differential, and culture (Evidence) (4352).
It is important to initiate empiric antibiotic therapy
for PD-associated peritonitis as soon as possible.
There are potentially serious consequences of peritonitis (relapse, catheter removal, permanent transfer
to hemodialysis, and death) that are more likely to
occur if treatment is not initiated promptly (Opinion).
Patients with peritonitis usually present with cloudy
fluid and abdominal pain; however, peritonitis should
always be included in the differential diagnosis of the
PD patient with abdominal pain, even if the effluent is
clear, as a small percentage of patients present in this
fashion. Other causes, such as constipation, renal or biliary colic, peptic ulcer disease, pancreatitis, and acute
intestinal perforation, should also be investigated in the
PD patient with abdominal pain and clear fluid. Conversely, while patients with peritonitis most often have
severe pain, some episodes are associated with mild or
even no pain. The degree of pain is somewhat organism
specific (e.g., generally less with CoNS and greater with
Streptococcus, gram-negative rods, S. aureus) and can
help guide the clinician in the decision to admit or treat
as an outpatient. Patients with minimal pain can often
be treated on an outpatient basis with IP therapy and
oral pain medication. Those requiring intravenous (IV)
narcotics always require admission for management.
Cloudy effluent will usually represent infectious peritonitis but there are other causes (48). The differential
diagnosis is shown in Table 3. Case reports of sterile peritonitis associated with icodextrin-based dialysis solutions have been reported from Europe (49). Randomized
TABLE 3
Differential Diagnosis of Cloudy Effluent
Many organisms can cause exit-site and tunnel infections, including micro-organisms belonging to the normal skin flora, such as corynebacteria (7,32). Therefore,
culture with sensitivity testing is important in determining antibiotic therapy. Close follow-up is necessary to
determine the response to therapy and relapse. Unfortunately, both S. aureus and P. aeruginosa catheter
infections tend to recur; repeating PD effluent cultures 1 2 weeks after the discontinuation of antimicrobial treatment may be useful for risk assessment.
Ultrasonography of the exit site is a useful adjunctive tool in the management of exit-site and tunnel infections (33). A sonolucent zone around the external
cuff over 1 mm thick following a course of antibiotic
treatment and the involvement of the proximal cuff are
associated with poor clinical outcome. In exit-site infections caused by P. aeruginosa, clinical outcome has
been uniformly poor irrespective of the sonographic
findings.
Antibiotic therapy must be continued until the exit
site appears entirely normal. Two weeks is the minimum
length of treatment time; treatment for 3 weeks is probably necessary for exit-site infections caused by P. aeruginosa. If prolonged therapy (e.g., longer than 3 weeks)
with appropriate antibiotics fails to resolve the infection, the catheter can be replaced as a single procedure
under antibiotic coverage (3437). If the cuffs are not
involved, revision of the tunnel may be performed in
conjunction with continued antibiotic therapy. This procedure, however, may result in peritonitis, in which case
the catheter should be removed. Sonography of the tunnel has been shown useful in evaluating the extent of
infection along the tunnel and the response to therapy
and may be used to decide on tunnel revision, replacement of the catheter, or continued antibiotic therapy
(38). In general, catheter removal should be considered
earlier for exit-site infections caused by P. aeruginosa or
if there is tunnel infection.
A patient with an exit-site infection that progresses
to peritonitis, or who presents with an exit-site infection in conjunction with peritonitis with the same organism, will usually require catheter removal. Catheter
removal should be done promptly rather than submitting the patient to prolonged peritonitis or relapsing
peritonitis. The exception is peritonitis due to coagulase-negative staphylococcus (CoNS), which is generally
readily treated. Simultaneous removal and reinsertion
of the dialysis catheter (with a new exit site) is feasible
in eradicating refractory exit-site infections due to
P. aeruginosa (39). In selected cases, cuff shaving may
be considered an alternative to catheter replacement for
tunnel infection (40).
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SPECIMEN PROCESSING
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Patient Education
Gram-positive coverage:
Either first-generation
cephalosporin or vancomycin
68 hours
Gram-negative coverage:
Either third-generation
cephalosporin or aminoglycoside
Figure 1 Initial management of peritonitis: *Continued assessment and modification of therapy based on culture and sensitivity
results; refer to subsequent sections for specific organisms cultured. Dwell time of the exchange for intermittent therapy must be
a minimum of 6 hours. Vancomycin may be considered if patient has a history of methicillin-resistant Staphylococcus aureus
colonization/infection, is seriously unwell, or has a history of severe allergy to penicillins and cephalosporins. If the center has an
increased rate of methicillin resistance, vancomycin may also be considered. If the patient is cephalosporin allergic, aztreonam
is an alternative to ceftazidime or cefepime. Vancomycin and ceftazidime are compatible when mixed in a dialysis solution volume
greater than 1 L; however, they are incompatible when mixed in the same syringe or empty dialysis solution bag for reinfusion.
Aminoglycosides should not be added to the same exchange with penicillins as this results in incompatibility.
(including coverage for Pseudomonas) will prove suitable. This protocol has been shown to have results
equivalent to vancomycin plus a second drug for gramnegative coverage (77,87). Many programs, however,
have a high rate of methicillin-resistant organisms and
thus should use vancomycin for gram-positive coverage
with a second drug for gram-negative coverage (88).
Gram-negative coverage can be provided with an
aminoglycoside, ceftazidime, cefepime, or carbapenem.
Quinolones should be used for empiric coverage of gramnegative organisms only if local sensitivities support such
use. For the cephalosporin-allergic patient, aztreonam
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06 hours
Outcomes Evaluation
LI et al.
400
is an alternative to ceftazidime or cefepime for gramnegative coverage if aminoglycosides are not used. Antibiotic resistance may develop with empiric use of
extended-spectrum cephalosporins and quinolones. Resistance should be monitored, especially for enterococci,
staphylococci, yeasts, and gram-negative organisms
such as Pseudomonas species, Escherichia coli, Proteus
species, Providencia species, Serratia species, Klebsiella
species, and Enterobacter species, but catheter removal
should not be delayed until the result of antibiotic resistance testing is available.
While an extended course of aminoglycoside therapy
may increase the risk for both vestibular and ototoxicity, short-term use appears to be safe and inexpensive
and provides good gram-negative coverage. Gentamicin
given in once-daily dosing (40 mg IP in 2 L) is as effective as dosing in each exchange (10 mg/2 L, IP, in 4 exchanges/day) for CAPD peritonitis (89,90). There does
not appear to be convincing evidence that short courses
of aminoglycosides harm residual renal function (65,91).
Repeated or prolonged courses (e.g., longer than
2 weeks) of aminoglycoside therapy are probably not advisable if an alternative approach is possible. If an
aminoglycoside is used for the initial gram-negative coverage, intermittent dosing is strongly encouraged and
prolonged courses of longer than 3 weeks should be
avoided.
Either ceftazidime or cefepime is an appropriate alternative for gram-negative coverage. Cefepime is not
broken down by many of the beta-lactamases that are
currently produced by gram-negative bacilli worldwide
so, theoretically, it has better coverage than ceftazidime.
In addition to the above combinations, a variety of
regimens have been tested in prospective trials, with
acceptable results (92). In a randomized control study
of 102 patients, IP cefazolin plus netilmicin and cefazolin
plus ceftazidime had similar efficacy as empirical treatment for CAPD peritonitis (93). In CAPD patients with
residual renal function, significant but reversible reduction in residual renal function and 24-hour urine volume
could occur after an episode of peritonitis, despite successful treatment by antibiotics. However, the effect of
both regimens on residual renal function is similar (93).
Other combination therapy may also be effective. A
recent study showed that systemic vancomycin and ciprofloxacin administration might also be an effective firstline antibiotic therapy (94). Lima et al. (95) reported
satisfactory response rates with ciprofloxacin plus
cefazolin as the empirical regimen for peritonitis. Meropenem plus tobramycin followed by meropenem plus vancomycin is another regimen recently reported to have
reasonable success (96), but this combination is too
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Little is known about intermittent dosing requirements in patients treated with APD. The optimal ratio of
antibiotic concentration and MIC value of a bacterium
depends on various variables, such as bacterial species,
presence of postantibiotic effect, and duration of antibiotic concentration above MIC value. The Committee
agrees that IP dosing of antibiotics for peritonitis is preferable to IV dosing in CAPD, since IP dosing results in
very high local levels of antibiotics. For example, 20 mg/L
IP gentamicin is well above the MIC of sensitive organisms. The equivalent dose of gentamicin given IV would
result in much lower IP levels. The IP route has the added
advantage that it can be done by the patient at home
after appropriate training and it avoids venipuncture.
Monitoring of drug levels for aminoglycosides and vancomycin is recommended if toxicity is suspected.
Intraperitoneal antibiotics can be given in each exchange (i.e., continuous dosing) or once daily (i.e., intermittent dosing) (109114). In intermittent dosing,
the antibiotic-containing dialysis solution must be
allowed to dwell for at least 6 hours to allow adequate
absorption of the antibiotic into the systemic circulation. Most antibiotics have significantly enhanced absorption during peritonitis (e.g., IP vancomycin is about
50% absorbed in the absence of peritonitis but closer to
90% in the presence of peritonitis), which permits subsequent reentry into the peritoneal cavity during ensuing exchanges of fresh dialysis solution. Table 4 provides
doses for both continuous and intermittent administration for CAPD, where there is information available.
There are insufficient data on whether continuous
dosing is more efficacious than intermittent for firstgeneration cephalosporins. A once-daily IP cefazolin
dose of 500 mg/L results in acceptable 24-hour levels in
the dialysis fluid in CAPD patients (111). An extensive
body of evidence exists for the efficacy of intermittent
dosing of aminoglycosides and vancomycin in CAPD but
less for APD. Table 5 provides dosing recommendations
for APD where such data exist or sufficient experience
can allow a recommendation to be made. A randomized
trial in children that included both CAPD and APD patients found that intermittent dosing of vancomycin/
teicoplanin is as efficacious as continuous dosing (65).
Intraperitoneal vancomycin is well absorbed when given
in a long dwell and subsequently crosses again from the
blood into the dialysate with fresh exchanges.
Rapid exchanges in APD, however, may lead to inadequate time to achieve IP levels. There are fewer data
concerning efficacy of first-generation cephalosporins
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TABLE 4
Intraperitoneal Antibiotic Dosing Recommendations for CAPD Patientsa
Continuous
(mg/L; all exchanges)
2 mg/kg
0.6 mg/kg
LD 25, MD 12
LD 8, MD 4
15 mg/kg
1000 mg
10001500 mg
1000 mg
LD 500, MD 125
LD 500, MD 125
LD 500, MD 125
LD 250, MD 125
ND
ND
ND
ND
LD 250500, MD 50
MD 125
LD 500, MD 250
LD 50000 units, MD 25000 units
ND
LD 50, MD 25
ND
ND
LD 1000, MD 250
LD 100, MD 20
1.5
2 g every 12 hours
LD 1000, MD 100
1 g b.i.d.
LD 250, MD 50
25 mg/L in alternate bagsb
Oral 960 mg b.i.d.
ND = no data; q.d. = every day; NA = not applicable; IP = intraperitoneal; b.i.d. = 2 times per day; LD = loading dose in mg/L; MD =
maintenance dose in mg/L.
a For dosing of drugs with renal clearance in patients with residual renal function (defined as >100 mL/day urine output), dose
should be empirically increased by 25%.
b Given in conjunction with 500 mg intravenous twice daily.
TABLE 5
Intermittent Dosing of Antibiotics in Automated Peritoneal Dialysis
Drug
IP dose
Cefazolin
Cefepime
Fluconazole
Tobramycin
Vancomycin
Aminoglycosides
Amikacin
Gentamicin, netilmicin, or tobramycin
Cephalosporins
Cefazolin, cephalothin, or cephradine
Cefepime
Ceftazidime
Ceftizoxime
Penicillins
Amoxicillin
Ampicillin, oxacillin, or nafcillin
Azlocillin
Penicillin G
Quinolones
Ciprofloxacin
Others
Aztreonam
Daptomycin (115)
Linezolid (41)
Teicoplanin
Vancomycin
Antifungals
Amphotericin
Fluconazole
Combinations
Ampicillin/sulbactam
Imipenem/cilastin
Quinupristin/dalfopristin
Trimethoprim/sulfamethoxazole
Intermittent
(per exchange, once daily)
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nificance (125). There was, however, a significant decrease in the incidence and proportion of antibioticrelated fungal peritonitis in the nystatin group (125).
The Work Group recognizes that nystatin is not available in some countries and that there are few data on
the efficacy and potential problem of fluconazole prophylaxis. Each PD program must examine its history of
fungal peritonitis and decide whether such a protocol
might be beneficial.
Studies of IP urokinase failed to show any benefit of
urokinase over placebo with respect to complete cure in
persistent peritonitis, or primary response to treatment
in the setting of resistant peritonitis (105,126,127).
Similarly, catheter removal and relapse rates were not
affected by treatment with urokinase, either in the setting of persistent peritonitis or on initiation of fibrinolytic therapy at the time peritonitis was diagnosed. In
contrast, one randomized control study showed that
simultaneous catheter removal and replacement was
superior to urokinase in reducing recurrent episodes of
peritonitis (128).
One, small, randomized control trial reported that the
use of IP immunoglobulin provides significant improvement in laboratory parameters (especially dialysate leukocyte count), but that there was no effect on the rate
of treatment failure or relapse (129).
SUBSEQUENT MANAGEMENT OF PERITONITIS
ADJUNCTIVE TREATMENTS
Once culture results and sensitivities are known, antibiotic therapy should be adjusted to narrowspectrum agents as appropriate. For patients with
substantial residual renal function (e.g., residual glomerular filtration rate 5 mL/minute/1.73 m2), the
dose of antibiotics that have renal excretion may need
to be adjusted accordingly (Opinion).
The majority of fungal peritonitis episodes are preceded by courses of antibiotics (116118). Fungal prophylaxis during antibiotic therapy may prevent some
cases of Candida peritonitis in programs that have high
rates of fungal peritonitis (119124). A number of studies have examined the use of prophylaxis, either oral
nystatin or a drug such a fluconazole, given during antibiotic therapy to prevent fungal peritonitis, with
mixed results. Programs with high baseline rates of fungal peritonitis found such an approach to be beneficial, while those with low baseline rates did not detect
a benefit. In a recent observational study, the fungal
peritonitis rate of the nystatin group was slightly lower
than that of the control group (0.011 vs 0.019/patientyear) but the difference did not reach statistical sig-
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REFRACTORY PERITONITIS
TABLE 7
Indications for Catheter Removal for Peritoneal
Dialysis-Related Infections
Refractory peritonitis
Relapsing peritonitis
Refractory exit-site and tunnel infection
Fungal peritonitis
Catheter removal may also be considered for
Repeat peritonitis
Mycobacterial peritonitis
Multiple enteric organisms
Treatments of relapsing, recurrent, or repeat peritonitis represent distinct clinical entities that portend
a worse outcome (particularly for recurrent peritonitis). Stronger consideration should be given to timely
catheter removal (Opinion) (133).
TABLE 6
Terminology for Peritonitis
Recurrent
Relapsing
Repeat
Refractory
Catheter-related peritonitis
An episode that occurs within 4 weeks of completion of therapy of a prior episode but with a different organism
An episode that occurs within 4 weeks of completion of therapy of a prior episode with the same
organism or 1 sterile episode
An episode that occurs more than 4 weeks after completion of therapy of a prior episode with the
same organism
Failure of the effluent to clear after 5 days of appropriate antibiotics
Peritonitis in conjunction with an exit-site or tunnel infection with the same organism or 1 site
sterile
Relapsing episodes should not be counted as another peritonitis when calculating peritonitis rates; recurrent and repeat episodes
should be counted.
404
organisms. Table 5 lists the most commonly used antibiotics that have been studied in APD and provides dosing
recommendations. Patients who are high transporters
and those with high dialysate clearances may have a more
rapid removal of some antibiotics. Adjustments in dosing for such patients are not yet known but the clinician
should choose the side of higher dosing.
Within 48 hours of initiating therapy, most patients
with PD-related peritonitis will show considerable clinical improvement. The effluent should be visually inspected daily to determine if clearing is occurring. If
there is no improvement after 48 hours, cell counts and
repeat cultures should be done. Antibiotic removal techniques may be used by the laboratory on the effluent in
an attempt to maximize culture yield.
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Coagulase-negative staphylococcus, especially S. epidermidis, is still a very common organism in many programs, usually denotes touch contamination, generally
responds well to antibiotic therapy, and is seldom related
to a catheter infection. Most patients with S. epidermidis
Assess clinical improvement, repeat dialysis effluent cell count and culture at days 35
Clinical improvement
(symptoms resolve; bags clear):
Continue antibiotics;
Reevaluate for exit-site or occult
tunnel infection, intra-abdominal
abscess, catheter colonization, etc.
No clinical improvement
(symptoms persist; effluent remains cloudy):
Reculture & evaluate*
Figure 2 Coagulase-negative staphylococcus (CoNS; Staphylococcus epidermidis): *CoNS can sometimes lead to relapsing peritonitis, presumably due to biofilm involvement. The duration of antibiotic therapy following catheter removal and timing of
resumption of peritoneal dialysis may be modified depending on clinical course.
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405
Coagulase-negative staphylococcus peritonitis, including S. epidermidis, is due primarily to touch contamination, is generally a mild form of peritonitis,
and responds readily to antibiotic therapy but can
sometimes lead to relapsing peritonitis due to biofilm
involvement. In such circumstances, catheter replacement is advised (Evidence) (Figure 2) (37,134136).
LI et al.
Staphylococcus aureus causes severe peritonitis. Although it may be due to touch contamination, it is
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Enterococcus/Streptococcus on Culture
Clinical improvement
(symptoms resolve; bags clear):
Continue antibiotics;
Reevaluate for exit-site or occult
tunnel infection, intra-abdominal
abscess, catheter colonization, etc.
Duration of therapy:
14 days (Streptococcus)
21 days (Enterococcus)
No clinical improvement
(symptoms persist; effluent remains cloudy):
Reculture & evaluate*
Figure 3 Enterococcus or Streptococcus peritonitis: *Choice of therapy should always be guided by sensitivity patterns. If linezolid
is used for vancomycin-resistant enterococcus, bone marrow suppression has been noted after 10 14 days. The manufacturers
precaution label states that these antibiotics should not be mixed together in the same solution container. Physicians own judgment is necessary. The duration of antibiotic therapy following catheter removal and timing of resumption of peritoneal dialysis
may be modified, depending on clinical course.
often due to catheter infection. Staphylococcal peritonitis with concurrent exit-site or tunnel infection
is unlikely to respond to antibiotic therapy without
catheter removal (Evidence) (Figure 4) (5,23,149).
Rifampicin could be considered as an adjunct for the
prevention of relapse or repeat S. aureus peritonitis
but the enzyme-inducer effect of rifampicin should
be considered in patients taking other medications
(Opinion) (150).
If the organism is S. aureus, very careful attention
must be paid to the exit site and tunnel of the catheter,
as the mode of entrance of this organism is often via the
catheter, although touch contamination is another
source. If the episode occurs in conjunction with an exit-
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Assess clinical improvement, repeat dialysis effluent cell count and culture at days 35
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Clinical improvement
(symptoms resolve; bags clear):
Continue antibiotics;
Reevaluate for exit-site or occult
tunnel infection, intra-abdominal
abscess, catheter colonization, etc.
Duration of therapy:
at least 21 days
No clinical improvement
(symptoms persist; effluent remains cloudy):
Reculture & evaluate
Figure 4 Staphylococcus aureus peritonitis: *If vancomycin-resistant S. aureus, linezolid, daptomycin, or quinupristin/dalfopristin
should be used. Teicoplanin can be used in a dose of 15 mg/kg every 5 7 days. In areas where tuberculosis is endemic, rifampicin use for treatment of S. aureus should be restricted. Refractory is defined as failure to respond to appropriate antibiotics
within 5 days. The duration of antibiotic therapy following catheter removal and timing of resumption of peritoneal dialysis may
be modified depending on clinical course. BW = body weight; PD = peritoneal dialysis.
In a recent review of 245 cases of S. aureus peritonitis, episodes that were treated initially with vancomycin
had a better primary response rate than those that were
treated with cefazolin (98.0% vs 85.2%, p = 0.001) but
the complete cure rate was similar (150). Adjuvant
rifampicin treatment for a period of 5 7 days was associated with a significantly lower risk for relapse or repeat S. aureus peritonitis than was treatment without
rifampicin (21.4% vs 42.8%). In this study, recent hospitalization was a major risk factor for methicillin resistance. However, it should be noted that rifampicin is a
potent inducer of drug-metabolizing enzymes and would
reduce the levels of many medications. Similarly, an
evaluation of 503 cases of staphylococcal peritonitis in
Australia found that the initial empiric antibiotic choice
Assess clinical improvement, repeat dialysis effluent cell count and culture at days 35
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If a program has a rate of culture-negative peritonitis greater than 20%, then the culture methods should
Pseudomonas aeruginosa peritonitis, similar to S. aureus peritonitis, is often related to a catheter infection
and in such cases catheter removal will be required. Two
antibiotics should always be used to treat P. aeruginosa peritonitis (Evidence) (Figure 6) (25,156,157).
Pseudomonas aeruginosa peritonitis is generally severe and often associated with infection of the catheter.
If catheter infection is present or has preceded peritonitis, catheter removal is necessary. Antibiotics must be
continued for 2 weeks while the patient is on hemodialysis. A large retrospective study of 191 episodes of
Pseudomonas peritonitis recently confirmed that
Pseudomonas peritonitis is associated with greater frequencies of hospitalization, high rates of catheter removal, and permanent transfer to hemodialysis but not
with increased death rates. Prompt catheter removal and
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Clinical improvement:
Continue antibiotic
Duration of therapy:
14 days
No clinical improvement
after 5 days:
Remove catheter*
Infection resolving
Patient improvement clinically
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Clinical improvement
(symptoms resolve; bags clear):
Continue antibiotics;
Duration of therapy:
at least 21 days
Catheter removal*
q
Continue oral and/or systemic
antibiotics for at least 2 weeks
No clinical improvement
(symptoms persist; effluent remains cloudy):
Reculture & evaluate*
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Other
E. coli, Proteus, Klebsiella, etc.
Stenotrophomonas
Clinical improvement
(symptoms resolve; bags clear):
Continue antibiotics;
Duration of therapy:
1421 days
No clinical improvement by
5 days on appropriate antibiotics
(symptoms persist; effluent remains
cloudy): remove catheter
Clinical improvement
(symptoms resolve; bags clear):
Continue antibiotics;
Duration of therapy:
2128 days
Figure 7 Other single gram-negative organism peritonitis: *Choice of therapy should always be guided by sensitivity patterns.
POLYMICROBIAL PERITONITIS
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Duration of therapy:
minimum 21 days based
on clinical response
Prolonged treatment with antifungal agents to determine response and to attempt clearance is not encouraged. Fungal peritonitis is serious, leading to death of
the patient in approximately 25% or more of episodes
(116,117). Some evidence suggests that prompt catheter
removal poses a lesser risk of death. A recent Australian
report analyzed 162 episodes of fungal peritonitis retrospectively (176): Candida albicans and other Candida
species were the most frequently isolated fungi. Compared with other micro-organisms, fungal peritonitis was
associated with higher rates of hospitalization, catheter
removal, transfer to hemodialysis, and death (176). Initial therapy may be a combination of amphotericin B and
flucytosine, until the culture results are available with
susceptibilities. An echinocandin (e.g., caspofungin or
anidulafungin), fluconazole, posaconazole, or voriconazole may replace amphotericin B based on species
identification and MIC values. Intraperitoneal use of
amphotericin causes chemical peritonitis and pain; IV
use leads to poor peritoneal bioavailability. Voriconazole
or posaconazole are alternatives for amphotericin B
when filamentous fungi have been cultured. Neither of
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LI et al.
414
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For refractory peritonitis and fungal peritonitis, simultaneous catheter replacement is not possible. The
optimal time period between catheter removal for infection and reinsertion of a new catheter is not known.
Empirically, a minimum period of 2 3 weeks between
catheter removal and reinsertion of a new catheter is
recommended, although some would recommend later
reinsertion in cases of fungal peritonitis.
After severe episodes of peritonitis, some patients are
able to return to PD. In other patients, adhesions may
prevent reinsertion of the catheter, or continuation on
PD is not possible due to permanent membrane failure.
In a recent review of 189 peritonitis episodes, Troidle
et al. (195) found that only 47% of the patients underwent a successful catheter reinsertion and, of those, only
34% remained on PD 1 year later. Unfortunately, it is difficult to predict who will have many adhesions and who
will not. Reinsertion of a new catheter should preferably
be done by laparoscopic approach or minilaparotomy so
that any adhesion can be directly visualized by the
surgeon.
PREVENTION OF FURTHER PERITONITIS
415
In clinical practice, the length of treatment is determined mainly by the clinical response. After initiation
of antibiotic treatment, clinical improvement should be
present during the first 72 hours. Patients having cloudy
effluent on appropriate antibiotics after 5 days have refractory peritonitis and should have their catheter
removed.
In patients with CoNS peritonitis and in patients with
culture-negative peritonitis, antibiotic treatment should
be continued for at least 7 days after the effluent clears,
and for no less than 14 days total. This means that 14 days
is usually adequate for treatment of peritonitis in uncomplicated episodes due to CoNS. In patients who respond slowly to the initial antibiotic therapy (especially
episodes caused by S. aureus, gram-negative peritonitis, or enterococcal peritonitis), a 3-week treatment is
recommended (whether the catheter is removed or not).
LI et al.
416
TABLE 8
Recommendations for Research in Peritoneal
Dialysis (PD)-Related Infections
Manuscripts should include the following information
Description of population
Connection methodology (spike, Luer lock, etc.)
Type of PD (CAPD with number of exchanges, CCPD, APD with
dry day)
Exit-site infection, tunnel infection, and peritonitis
definitions
Use of standard definitions for repeat, recurrent, relapsed,
refractory, and cured peritonitis
Use of a standard definition for peritonitis-associated death
Exit-site care protocol
Staphylococcus aureus prevention protocol, if there is one
Training protocol
Proportion of patients requiring a helper
Proportion of patients who are carriers for all studies of
Staphylococcus aureus
Peritonitis rates: overall and for individual organisms
Power calculations for determining the number of patients
required for evaluation of an outcome
Detailed antimicrobial regimen description to include
agents, doses, frequency of administration, duration, route,
concomitant serum and dialysate levels (specify peak,
trough, mean, other)
CAPD = continuous ambulatory PD; CCPD = continuous cycling
PD; APD = automated PD.
overall rate but also as individual rates rather than percentages of infections due to specific organisms. Terminology for relapsing and refractory peritonitis as well as
primary cure should be kept constant. Multicenter
studies will probably be needed to enable recruitment
of the number of patients required to answer most of
these questions.
DISCLOSURES
Philip Kam-Tao Li has participated in clinical trials with
Baxter. Cheuk-Chun Szeto declares no conflict of interest. Judith Bernardini is a consultant with Baxter Healthcare. Ana Figueiredo has received speakers honoraria
from Baxter and travel sponsorship from Baxter and Fresenius. David Johnson has received speakers honoraria
from Baxter and Fresenius and has participated in clinical trials with Baxter, Fresenius, and Gambro. He has
been a consultant to Baxter and Gambro and has received
travel sponsorships from Baxter and Fresenius. He is also
the recipient of a Baxter Extramural Research Grant. Dirk
Struijk has received lecturing honoraria from Baxter and
has participated in clinical trials with Baxter.
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