Peritoneal Dialysis (PD) Associated Peritonitis Protocol (Edinburgh)
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Introduction
PD Associated peritonitis is a major cause of morbidity and technique failure for patients on PD. Rates vary across units and the world and adherence to evidence based guidelines has been shown to be poor. The international Society for Peritoneal Dialysis (ISPD) provide detailed, evidenced based guidelines to guide best practice and improve patient outcomes.
Scotland has consistently reported peritonitis rates above ISPD suggested standard of less than 0.4 episodes per patient year on PD, but rates vary between units. By aligning the peritonitis treatment protocols across Scottish PD units using the ISPD recommendations it is hoped that peritonitis rates will improve. (Reference: ISPD Guidelines 2022)
ISPD recommend ongoing audit of the following measures:
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Audit Measure Audit Standard/Target
- Units’ peritonitis rates* Less than 0.4 episodes per year on PD
- Culture negative peritonitis rate Less than 15%
- Outcome of peritonitis 80% cure rate
- Proportion of patients free from peritonitis 80% per year
- Organism specific peritonitis rate No target, report number of cases/year
- Time to first peritonitis No target, report mean time to first
- Peritonitis associated technique failure No target, report % of peritonitis episodes
- Peritonitis associated death No target, report % of peritonitis episodes
*In the case of relapsing peritonitis, only the initial case is counted with relapses considered a continuation of the first episode rather than separate episodes for data collection purposes.
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Definitions
PD-associated peritonitis
This can be diagnosed when at least two of the following are present:
- Clinical features consistent with peritonitis (abdominal pain, cloudy dialysis fluid)
- Dialysis fluid white cell count >100/µlitre (or mm3) with >50% polymorphonuclear leucocytes (PMNs)
- Positive culture from dialysis fluid
Relapsing peritonitis
Defined as further episode of peritonitis caused by the same organism (or culture negative) occurring within 4 weeks of completing antibiotic therapy for peritonitis.
Recurrent peritonitis
A further episode of peritonitis caused by a different organism, occurring within 4 weeks of completing antibiotics for peritonitis.
Repeat peritonitis
Defined as a further episode of peritonitis more than 4 weeks after completing antibiotics, with the same organism.
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Outcome of Peritonitis
Following an episode of peritoneal dialysis related peritonitis is classified as:
Medical Cure. Complete resolution of peritonitis together with NONE of the following complications: relapse, recurrent peritonitis, catheter removal, transfer to haemodialysis for ≥30 days or death.
Refractory; Peritonitis episode with persistently cloudy bags or persistent dialysis fluid count >100/µlitre (or mm3) after 5 days appropriate antibiotic therapy resulting in catheter removal.
Patient death. This includes patients who die within 30 days of presentation of peritonitis even if the effluent WCC had cleared.
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Prevention of Peritonitis
MSSA screening/eradication
Patients should have nasal swab for MSSA screening before PD catheter insertion and every 6 months. If swab positive for MSSA they should be offered MSSA eradication with nasal mupirocin and chlorhexidine or alternative wash (see separate protocol for MSSA screening and Eradication).
Exit site antibiotic cream
Patients should apply prophylactic cream (either gentamicin or mupirocin) daily to the catheter exit site to reduce the risk of exit site infection.
Antibiotics pre-operatively for PD catheter insertion
Intravenous antibiotics must be given ahead of PD catheter insertion. Vancomycin 1g iv pre-operatively (can be given at end of haemodialysis (HD) session previous day if on HD before PD). Alternatively, Teicoplanin 400mg iv can be administered pre-operatively.
Management of Invasive procedures (colonoscopy, gastroscopy, gynaecological intervention)
There is a high risk of peritonitis for patients undergoing gastroscopy (<4%), colonoscopy (<8.5%) or invasive gynaecological procedures (<38%) if a patient’s abdomen is not drained dry of dialysis fluid and they are not given prophylactic antibiotics to cover gram positive and negative organisms.
Patients must therefore drain all PD fluid and be given intravenous ceftriaxone 1 gram (or cefazolin 1 gram) before these procedures.
Management of possible contamination episodes
Possible contamination episodes include: leaks or breaks in tubing, leaks from dialysate bags, breach of aseptic technique or touch contamination of the connection during an exchange. Most commonly this would involve gram positive organisms. Patients should be told to contact PD team (or ward if out of hours) who should review the patient. PD fluid should be sent for WCC and in blood culture bottles for culture. The extension set should be changed if touch contamination or tubing damage has occurred. Prophylactic antibiotics should be given – vancomycin 1g give IP for 6 hour dwell (or if allergy to Vancomycin alternative options are Cefazolin 1 gram IP or Teicoplanin 400 mg IP for a 6 hour dwell).
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Diagnosis of Peritonitis
Take history, identifying possible episodes of contamination or recent PD-related infections.
Clinical assessment of patient with temperature, BP, heart rate, and examination of abdomen looking for evidence of exit site/tunnel infection.
Essential samples:
- Send minimum 1x universal container to microbiology for urgent WCC and gram stain
- Send PD fluid in blood culture bottles (10mls per bottle) labelled “PD Fluid”
- If exit site exudate present, swab and send for culture
Notes:
Ensure sample is taken after a minimum 2 hour dwell time. If abdomen dry, fill with 1 litre dwell for 2 hours then send samples after draining.
Microbiology laboratories will have standard operating protocols for culturing PD fluid. When Cultures remain negative after 3-5 days incubation, further samples should be sent for cell count, differential cell count, alongside discussion with microbiology.
If there are concerns about potential mycobacterial or fungal peritonitis this must be discussed with microbiology as specific sampling and culture methods are required and standard culture methods will not identify these organisms.
If your unit’s culture negative rate is >15% of peritonitis episodes this should prompt a review of your PD fluid sampling and culture methods.
If PD fluid is cloudy but the WCC <100 µlitre or <50% PMNs, consider alternative causes of cloudy fluid (see Appendix 1). ______________________________________________________________________
Initial Antimicrobial Treatment
Antibiotic therapy should be initiated as soon as possible when WCC is found to be >100 µlitre.
If clinical suspicion is high (eg abdominal pain and cloudy bag) and/or patient is unwell with evidence of sepsis, antibiotics can be given immediately after samples are taken, before PD cell count result.
Antibiotic therapy must cover both gram negative and gram positive organisms.
All intra-peritoneal (IP) antibiotics should be given via PD exchanges with a minimum dwell 6 hours.
Initial Antibiotics:
- Vancomycin 30mg/kg (maximum 3g) IP and
- Ceftazidime 1.5g IP in 2 litre bag
Notes:
APD patients do not need to convert to CAPD.
Treatment can be inpatient or outpatient at the discretion of the treating team, based on the patient’s clinical condition, frailty, social factors and practicalities of providing outpatient antibiotics.
Ceftazidime and Vancomycin can be given in to the same bag and are compatible with standard glucose bags and icodextrin.
If the PD catheter is not working, antibiotics should be given IV instead to cover gram positive and gram negative organisms (suggest iv vancomycin and cephalosporin).
If allergy to Vancomycin, Teicoplanin 15mg/kg every 5 days or cefazolin 15mg/kg daily can be used instead.
If allergy to Ceftazidime, Gentamicin 0.6 mg/kg can be given but note the risk of ototoxicity and vestibular toxicity so serum gentamicin level should be checked at 24 hrs. If level <2 a further dose can be given. If level >2, no dose given and repeat level at 48 hours post-dose and re-dose when <2. The timing of subsequent doses and level checks should be based on this. Continuing gentamicin for >14 days is not recommended but should be a decision made after consideration of the relative risks and considering alternative antibiotic options.
Alternative antibiotics and their dosing/stability in PD fluid is shown in Appendix 2 and 3.
If previous clostridium difficile infection, consider Aztreonam 3g IP daily instead of Ceftazidime.
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Fungal Prophylaxis
To prevent fungal peritonitis anti-fungal prophylaxis should be co-prescribed for the duration of antibiotics given for PD associated peritonitis.
- Fluconazole 200mg PO on alternate days
If there are concerns about potential drug interactions, Nystatin (100,000 units/ml), 5 mls 4 x per day can be used as an alternative for fungal prophylaxis.
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Ongoing Antibiotic Therapy and Monitoring
Both gram Vancomycin and Ceftazidime should be continued until culture results are available.
Antibiotic treatment is a minimum of 2 weeks with ongoing antibiotic therapy and duration according to organism cultured (see relevant organism flow chart below under “Organism Specific Management”).
For those that culture an organism, >75% of cases the bacteria will be identified by day 3.
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Vancomycin Dosing
- Vancomycin dose is 30mg per kg (maximum 3g) given in minimum 6 hour dwell.
- The same dose is repeated when the vancomycin level falls <20.
Patients with residual kidney function (see most recent PD adequacy test result) will clear vancomycin more rapidly and need more frequent dosing. Patients on APD may clear vancomycin more quickly than on CAPD.
Patients at extremes of weight may need more or less frequent dosing to maintain levels.
The expectation is that most patients will need at least 3 doses vancomycin to cover 2 weeks of treatment.
Vancomycin Monitoring
- Vancomycin trough target level is 15-20.
If a patient is being treated as an inpatient, check levels each day until it is clear how quickly they are clearing the vancomycin.
If outpatient, check first vancomycin level day 2 (48 hours) after initial dose. If above 20, recheck trough 24 hours later, and every 24 hours until level drops <20 and a second dose is given.
The timing of subsequent vancomycin level checks (and therefore re-dosing) will be determined by how quickly the vancomycin level dropped <20 mg/l and will require clinical judgement eg if a second vancomycin dose was needed on day 2 (48 hours after the first dose) then aim to check next vancomcyin level on day 4 (48 hours after second dose).
Trough levels <12 are associated with poorer outcomes, so timing of vancomycin trough testing and re-dosing should aim to avoid the level dropping <12.
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Specific Scenarios
Pre-PD Peritonitis
This is defined as peritonitis occurring after PD catheter inserted but before patient has commenced PD treatment (in practice this is first day of training or inpatient PD). To obtain samples, fill with 1 litre dwell for 2 hours then send samples after draining.
APD/dry abdomen
If abdomen dry, fill with 1 litre dwell for 2 hours then send samples after draining.
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Indications for Catheter Removal
The decision to remove the PD catheter must be made on a case by case basis by the clinical team, but is recommended in the following circumstances:
- Fungal peritonitis (catheter must be removed in all cases, as soon as possible)
- Refractory peritonitis (ie no clinical improvement by day 5)
- Relapsing, recurrent or repeat peritonitis*
- Refractory exit site and/or tunnel infection
*At the discretion of the treating clinician but ISPD recommendation is after 2nd episode of staphylococcus aureus, 2nd episode pseudomonas, 3rd episode coagulase negative staphylococci (even if responding to treatment).
If catheter is removed, appropriate antibiotic (minimum 14 days) or fungal therapy (minimum 14 days) should be continued. This could be iv or oral according to clinical condition and microbiology advice.
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Timing of Catheter Replacement after removal for infection
Concomitant catheter removal and replacement is reasonable in the context of relapsed infection where the cause is thought to be a biofilm (typically infection episodes with the same organism, relapsing quickly after antibiotics stopped. In this situation it should be done under antibiotic cover when the infection is treated (PD WCC <100/mm3) and in the absence of simultaneous exit site or tunnel infection).
When the catheter is removed in the context of refractory peritonitis the catheter should not be replaced until antibiotics are complete and the infection has resolved (duration of antibiotics will be determined by the organism cultured and clinical condition of the patient). This is a clinical decision which should take in to consideration the alternative dialysis options for the patient.
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Management after peritonitis episode
Review technique and consider further training.
Consider planning vascular access as back up if patients are experiencing multiple infective episodes.
Standard Operating Procedure (SOP) for outpatient antibiotic treatment of Peritonitis
Each unit should agree an SOP for providing IP antibiotics as an outpatient, monitoring of patients include the checking of antibiotic levels and repeat PD fluid sampling (see separate section on EDREN)
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Organism-specific Antibiotic Treatment Summary (see separate flow charts for detail)
Culture negative 2 weeks vancomycin and ceftazidime
Gram positive cocci 2 weeks vancomycin, stop ceftazidime
MSSA or MRSA 3 weeks vancomycin, stop ceftazidime
Streptococcus 2 weeks vancomycin, stop ceftazidime
Corynebacterium 2 weeks vancomycin, stop ceftazidime (If repeat episode, give 3 weeks vancomycin)
Pseudomonas 3 weeks, stop vancomycin, needs 2 antibiotics (according to sensitivities: DW micro)
Acinetobacter 3 weeks, stop vancomycin, DW micro: meropenem or co-trimoxazole
Stenotrophomonas 3 weeks, stop vancomycin, requires 2 antibiotics (according to sensitivities: DW micro)
Polymicrobial 3 weeks (consider GI pathology), antibiotics to cover all organisms
Enteric gram negative 3 weeks, stop vancomycin, ceftazidime IP pending sensitivities
Serratia marcescens 3 weeks, stop vancomycin, (IP meropenem or oral ciprofloxacin)
Citrobacter 3 weeks, stop vancomycin, (IP meropenem or oral ciprofloxacin)
Morganella morgani 3 weeks, stop vancomycin, (IP meropenem or oral ciprofloxacin)
Enterobacter cloacae 3 weeks, stop vancomycin, (IP meropenem or oral ciprofloxacin)
ESBL- producing 3 weeks, stop vancomycin, (IP meropenem or oral ciprofloxacin)
CPE 3 weeks, stop vancomycin, seek microbiology advice
Fungal Catheter removal ASAP then 2 weeks treatment as per sensitivities
Pasteurella multocida 2 weeks, stop vancomycin, ceftazidime IP or co-amoxiclav (PO)
Gordonia 3 weeks, stop vancomycin, 2 antibiotics (meropenem +gentamicin)
Mycobacteriae Discuss with microbiology and infectious diseases specialist