• Summary
  Click here to print a Quick Reference Guide
• Background
• Clinical Diagnosis
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Switch to oral agent(s)
• Treatment Failure

Clinical features of peritoneal dialysis (PD) peritonitis include:

• cloudy dialysate
• abdominal pain
• fever
• nausea and diarrhoea
• PD catheter exit site may show features of an exit site infection

Initial investigations required
PD fluid sample for white cell count and microbiology – specialist nurse collection only;
Exit site swab for culture;
Blood cultures (only if systemic signs of infection);
FBC, U&E, CRP.

Non-Antimicrobial Management
For heparin use, PD regimen and PD catheter/removal – see full guideline

Empirical (initial) antimicrobial treatment
Vancomycin (given as a single intraperitoneal loading dose dependent on weight, see below). This should be given in a volume of 2 litres dialysate for a minimum six hour dwell. However, it may be given in 1.5 litres of dialysate if larger volumes are not tolerated.
Patients > 45kg 2g dose of Vancomycin as above
Patients < 45kg 1.5g dose of Vancomycin as above
AND Ciprofloxacin 500mg 12-hourly oral route.

See full guideline for more details and in case of allergy to these agents.

Referral criteria for specialist input
Management of PD peritonitis must be under the supervision of a specialist renal unit with experience of managing peritoneal dialysis patients. All suspected cases presenting elsewhere should be urgently discussed with the Renal Unit for advice about investigation and management. This guideline refers specifically to the adult Renal Unit (which may include those aged 16-18 years who are under the care of the adult unit).

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Peritoneal dialysis (PD), comprising CAPD and APD, is a major modality for treatment of patients with end-stage renal failure. It involves infusion of dialysis fluid into the peritoneal cavity via a permanent catheter. Peritonitis is one of the major complications of PD and can lead to severe acute and long-term effects. Infections may arise through contamination during the dialysis procedure, spread of infection from the catheter exit site from the abdominal wall, and through intra-abdominal sources such as infection with enteric organisms. The varied pathogenesis and involvement of an indwelling medical device (PD catheter) mean that a wide variety of microorganisms can cause PD peritonitis. Staphylococci (Including Staphylcoccus aureus and coagulase negative staphylococci) are a common cause but Gram negative bacteria including Pseudomonas species may also be involved.

“Secondary peritonitis”, resulting from perforation of intestine or a primary focus of infection in another intra-abdominal organ, requires a different antimicrobial approach and usually surgical input and should be managed according to LTHT guideline for management of intra-abdominal infection of unknown cause.

The following document describes the standard protocol for treatment of peritonitis in patients on CAPD and APD in the adult Renal Unit in Leeds.

It is essential that the protocol is routinely followed, and that any necessary deviations are discussed with the Renal and Microbiology consultants and PD nursing staff to allow a consistent approach and a rational approach to future revision of the protocol.

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Clinical features of peritoneal dialysis (PD) peritonitis include the following in a PD patient:

• cloudy dialysate
• abdominal pain
• fever
• nausea and diarrhoea.

The PD catheter exit site may show features of an associated exit site infection (including purulent exudate, erythema and tenderness).

Rarely PD peritonitis may present as abdominal pain with clear dialysate. In this situation other causes of abdominal pain should be sought, but a subsequent dialysis dwell will yield cloudy dialysate with an increased dialysate white cell count (WCC) in a patient who does have peritonitis.
Other causes of cloudy dialysate include:

• Eosinophilic peritonitis
• Haemoperitoneum
• Chemical peritonitis
• Malignancy
• Chylous dialysate
• Specimen from “dry” peritoneal cavity

An elevated dialysate white cell count (WCC) of > 0.1 white cells x 109/litre of which at least 50% are neutrophils is supportive of the diagnosis of peritonitis- see investigation section below.

Note that the differential white cell count from automated analysis may indicate a relative lower proportion of white cells as neutrophils, than accurate manual counts, so do not withhold antibiotic treatment on the basis of WCC differential where there is an elevated WCC but <50% neutrophils, unless there is also reason to suspect this is not an infection (e.g. a sample from dry peritoneal cavity or borderline total white cell count).

Patients with generalised peritonism or severe sepsis – may have secondary peritonitis and require surgical assessment and should be assessed as according to the Trust sepsis guideline.

Specialist referral

• All patients on PD with suspected or possible PD peritonitis require URGENT review by the Renal Unit to allow collection of appropriate samples (which should be collected by renal nurses trained in PD) and management by the multidisciplinary PD team. Where need for review is in doubt, or a patient is too ill for immediate transfer from another site, this should be urgently discussed with the Renal Team for further advice

Establishing the cause of peritonitis

• All patients presenting with PD peritonitis should be questioned about any history of a technique error or recent acute illness or symptoms (especially GI, urological).
• The presence of symptoms and signs of PD catheter exit-site infection should be determined
• Reassessment of PD technique and follow up home visit is essential following an episode of PD peritonitis, with any necessary supplementary patient training undertaken and further follow up technique assessment performed.

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1. Recommendation: PD effluent should be investigated in all suspected cases of PD peritonitis; send:
   • 5mL dialysate in EDTA tube for white cell count (WCC) and differential to Haematology
   • 20 mL dialysate for Gram stain and culture to Microbiology
   • 8 mL dialysate into each of a pair of blood culture bottles for culture (i.e. 2 x 8mL samples). See later in this section for interpretation.

   Samples for WCC and Gram stain should be requested and processed urgently.
   N.B PD fluid samples should only be taken by appropriately trained nephrology nurses.
   [Evidence level C]

2. Recommendation: If the diagnosis of peritonitis on presentation is uncertain (e.g. only slightly hazy dialysate), send samples for white cell count only initially; then send the remainder of fluid samples if the white cell count confirms diagnosis of peritonitis.
   [Evidence level C]

3. A PD catheter exit site swab should be sent from PD patients with peritonitis.
   Results can influence the decision to remove or later replace PD tube.
   [Evidence level C]

4. Recommendation: Blood samples should be sent for routine biochemistry, CRP and full blood count.
   [Evidence level D]

5. Recommendation: Blood cultures should not be sent routinely; only if there are features of systemic sepsis (e.g. pyrexia, chills, sweats, rigors, new confusion). Where there are features suggesting severe sepsis assessment and management will involve the Trust sepsis guidelines.
   [Evidence level D]

[NB – in patients with a suspected primary intra-abdominal pathology, serum amylase may be unreliable in diagnosis of pancreatitis in patients receiving icodextrin dialysate (Extraneal), which results in reduction in measured levels]

Interpretation of PD effluent analysis

Recommendation: An elevated dialysate WCC of > 0.1 white cells x 10⁹/litre of which at least 50% are neutrophils is supportive of the diagnosis of peritonitis and the need for immediate initiation of antibiotic treatment.
[Evidence level B]

This is the universally agreed diagnostic criteria for diagnosis of PD peritonitis^1,2.

The following should also be noted

• The same diagnostic criteria apply to diagnosis of APD and CAPD peritonitis. Fluid from short (overnight) dialysis cycles in APD may have misleadingly low WCCs. In equivocal cases a further exchange of minimum 1-2 hour dwell is adequate to obtain further samples for diagnostic white cell counts and Microbiology.
• Initial drainage of fluid after a period of a dry peritoneal cavity may have an elevated WCC, but predominantly comprised of monocytes. If in doubt a second dialysate sample should be sent for WCC after a further 1-2 hour dwell.

Recommendation: Monitoring fluid white cell counts

• After presentation, as a minimum, the patient should be reviewed the following day with repeat fluid WCC, then 3 days after the start of treatment, and every 3 days until completing antibiotics.
• Review and monitoring must be more frequent
• if patient is unwell
• if WCC is rising (including where Day 1 WCC > presentation WCC)
• peritonitis is slow to respond (clinical decision depending on symptoms and rate of decline of PD fluid WCC).
• A final dialysate sample, for WCC only, should be sent 1 week after stopping antibiotics following resolution of peritonitis.

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Recommendation for use of heparin

• Heparin 500 units/litre is added to an exchange if visible fibrin is present in the dialysate.

Recommendations regarding PD regime

• Patients usually remain on their usual PD modality (CAPD or APD).
• It may be necessary to interrupt or delay night cycles of APD in order to administer the initial 6 hour dwell containing Vancomycin .
• The use of rapid short cycles for initial treatment of peritonitis to “clear turbid effluent” is not beneficial to clearance of infection. However it may occasionally be of use if there is poor dialysate drainage.
• In the case of loss of ultrafiltration, more frequent, shorter duration glucose fluid exchanges (or icodextrin-containing dialysate for the long dwell in patients not already receiving it) may be considered as alternatives to using more hypertonic glucose solutions.
• Set change is not routinely required in a patient presenting with peritonitis (unless there is definite recent contamination of set line).

PD catheter removal or exchange in peritonitis

• If infection is severe or unresponsive to appropriate antibiotics the PD tube may need to be removed [Evidence level B].
• This should be considered if there is failure of PD effluent to clear within 5 days of treatment with appropriate antibiotics. This is important to prevent morbidity and to protect the peritoneal membrane, increasing the chance of a successful subsequent return to PD.

PD catheter removal or exchange is indicated to prevent further episodes in:

• Relapsing peritonitis (an episode of peritonitis within 4 weeks of completion of treatment of a prior episode with the same organism)
• Catheter-related peritonitis (peritonitis with an exit-site or tunnel infection with the same organism)

In these situations it is appropriate to perform simultaneous removal of the PD catheter and insertion of a new catheter on the contralateral side of the abdomen. This must only be performed after the dialysate WCC has normalised and the procedure must be performed with cover by an antibiotic active against the infecting organism (including on-going continuation/conclusion of the course of antibiotics for the episode of peritonitis). (See PD catheter insertion protocol).

If the catheter is removed rather than replaced (e.g. if the infection does not resolve with appropriate antibiotics), the patient may require temporary haemodialysis (if required, follow current protocol for decolonisation prior to HD line insertion). However, it is sometimes possible to hold without dialysis, with careful biochemical and clinical monitoring of the patient until a new PD catheter is inserted, if they have sufficient residual renal function. In cases where direct catheter exchange is performed, PD should ideally be withheld for 7-10 days to allow catheter healing. If there is insufficient residual renal function to allow this, PD is started earlier (timing determined by biochemistry and clinical features), using reduced volume dialysis exchanges and a “dry day” in APD patients³.
[Evidence level C].

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Recommendation: Initial antibiotic treatment of PD peritonitis:
Administer immediately Vancomycin and Ciprofloxacin as below until culture results are known (unless known allergy to either agent). This is in keeping with expert recommendations that initial antibiotic regimes should cover Gram positive and Gram negative organisms including Pseudomonas species^1,4.Our own audits in Leeds demonstrate that microbial resistance to this standard initial antibiotic regime is uncommon (<5% of episodes).
[Evidence level C]

• Vancomycin (given as a single intraperitoneal (IP) loading dose dependent on weight, see below). This should be given in a volume of 2 litres dialysate for a minimum six hour dwell. However, it may be given in 1.5 litres of dialysate if larger volumes are not tolerated. Give a 2g dose of Vancomycin as above unless the patient weighs <45kg in which case the dose should be 1.5g dose of Vancomycin .
  

AND

• Ciprofloxacin
  500mg 12-hourly given by oral route.
  
  (If there is concern about absorption of oral Ciprofloxacin (e.g. ileus or vomiting), patients should receive intravenous Ciprofloxacin 200 mg 12-hourly.
  
  Absorption of Ciprofloxacin is reduced by sevelamer, calcium compounds, oral iron, zinc, magnesium and milk. It should therefore be given at least 2 hours before any of these.

Deviations from standard initial antibiotic protocol
(only in consultation with senior Medical and Microbiological staff)
Initial antimicrobial regimes may be amended due to:

• Gram Stain
• Unusual findings on Gram stain (e.g. multiple organisms or fungi) may occasionally lead to individualised addition to / modification of regime, following senior Medical and Microbiological consultation.
• Components of the initial regime (i.e. Gram positive and Gram negative cover) must not be omitted on the basis of a positive Gram stain alone, and both should be continued until definitive (i.e. full culture and sensitivity) Microbiology results are available (rather than premature discontinuation of an agent).
• Recent history of peritonitis or exit-site/tunnel infection with an organism resistant to Vancomycin and ciprofloxacin
• Possibility of primary intra-abdominal pathology such as diverticular disease (in which case add Metronidazole for anaerobic cover)
• Allergy to Vancomycin and/or Ciprofloxacin (see below)

Drug allergies to Vancomycin or ciprofloxacin

• Ciprofloxacin allergy,
  Substitute with IP Gentamicin to provide Gram-negative cover (in addition to Vancomycin ).
• Vancomycin allergy,
  Substitute with either IP Teicoplanin , or in the case of previous anaphylactic reaction to vancomycin, with Linezolid (either IV or oral) following discussion with Microbiology.

(See Appendix 1 for more specific information on prescribing the following antimicrobials)

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Recommendation: Antimicrobial therapy should be reviewed and amended as necessary when microbiology results are available (see recommendations below)
[Evidence level D]

No bacterial growth:
In most cases this will be due to Gram positive organisms arising from touch contamination and will respond to appropriate antibiotics. If patient is responding to initiation regime, continue vancomycin as for coagulase negative staphylococci and discontinue ciprofloxacin^{1, 5}.

If culture-negative infection not responding to antibiotics:

• Consider non-infective causes
• Consider altering antibiotics suggested by recent positive exit-site culture or recent peritonitis (where possibility this is a relapse)
• Otherwise may require catheter removal
• Additional microbiological testing, following discussion with microbiology e.g. mycobacterial culture.

[Evidence level .B.]

Coagulase negative staphylococci
Continue intermittent intraperitoneal (IP) Vancomycin dwells according to blood levels at 3 day intervals (see info later) and stop oral ciprofloxacin¹.
[Evidence level C.]

Staphylococcus aureus (methicillin susceptible, MSSA)
Continue Vancomycin (as in coagulase negative staphylococci regime). There should be a low threshold for adding oral Rifampicin (300mg 12-hourly) orally after confirming sensitivity with results server or Microbiology unless very rapid clinical response^1,6
[Evidence level C]

Staphylococcus aureus (methicillin resistant, MRSA)
Continue Vancomycin (as in coagulase negative staphylococci regime). There should be a low threshold for adding oral Rifampicin (300mg 12-hourly) orally after confirming sensitivity with results server or Microbiology unless very rapid clinical response^1,6
[Evidence level C]

Enterococcal infection
Consider addition of Gentamicin where inadequate response to initial antibiotics¹.
[Evidence level C]

Gram negative infection (other than Pseudomonas)
If patient is responding, continue oral Ciprofloxacin and give no further vancomycin.
If unsatisfactory response, change to, or add, other IP antibiotic according to sensitivities (and discuss with seniors) ¹.
[Evidence level C]

Pseudomonas
Should be treated with two agents with activity against the cultured organism ^{[1, 7]}. This is usually

• oral (or iv) Ciprofloxacin + either IP Gentamicin or IP Ceftazidime
• Note that Ceftazidime and Gentamicin may not be compatible when given together IP in the same bag of dialysis fluid

[Evidence level B]

Fungal infections

• The PD catheter should be removed promptly.
• A minimum of 2 weeks of appropriate antifungal treatment is required from after the time of catheter removal.
• We recommend initial treatment of fungal PD peritonitis pending identification and sensitivity results as follows: Anidulafungin as initial treatment (200mg loading dose, then 100mg daily, intravenously). Treatment may be adjusted according to sensitivity
• Individual cases always require discussion with the Consultant Nephrologist and Microbiologists and anidulafungin will require a Microbiology prescription code.

[Evidence level D]

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• Minimum duration of treatment with appropriate antibiotics is 14 days¹.
• Antibiotic treatment should also continue until PD fluid WCC has been persistently <0.1 white cells x 10⁹/litre for at least 7 days.
  Thus total duration of treatment may be extended beyond 14 days if infection is slow to respond and time to normalisation of PD white cell count is >7 days, but should never be less than 14 days.

[Evidence level C.]

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Most treatment is IP, oral agents may be advised as adjuncts for specific pathogens, see directed antimicrobial section.

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Initial Management of Suspected PD Peritonitis

Suspected PD peritonitis Cloudy dialysate and/or abdominal pain Specimens for Microbiology/Haematology/Chemical Pathology (PD fluid suitable for WCC estimation after minimum 1 hour dwell) 5ml for white cell count (WCC) and differential (in EDTA tube to Haematology) Samples (await initial WCC if disgnosis uncertain): 20ml dialysate in blood culture bottles to Microbiology for culture sensitivity Exit-site swab and routine biochemistry (inc CRP) and FBC Peritonitis confirmed by WCC >0.1 x 109/litre of which at least 50% are neutrophils Initiate antibiotics Vancomycin 2g in 6 hour intraperitoneal dwell (1.5g if patient weighs <45kg) Ciprofloxacin 500mg bd orally May be modified in event of allergy, recent peritonitis, positive exit-site cultures, or if initial Gram stain suggests fungal infection or primary intra-abdominal pathology (see later).

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See empirical and directed antimicrobial sections or discuss with microbiology

Audit
The unit’s peritonitis data will be audited on an annual basis. Key audit measures are:

• Peritonitis rate (guidelines suggest that a rate of less than 1 episode / 18 patient treatment months is obtained)
• Rate of culture negative infections (guidelines suggest that inability to culture the responsible organism should occur in less than 20% of episodes)
• Cure rate of peritonitis with preservation of catheter and continuation of PD
• Relapse / recurrence rate
• Antibiotic sensitivity/resistance

Antibiotic doses
Doses of IP. antibiotics:

Doses of oral medication used in treatment of PD peritonitis:

• Ciprofloxacin 500mg 12-hourly
• Rifampicin 300mg 12-hourly
• Linezolid 600mg 12-hourly (following discussion with Microbiology – an antibiotic code will be required).

Patients treated with Rifampicin require monitoring of liver function tests and CSM advises that weekly FBC is required due to haematological side-effects in patients treated with Linezolid .

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