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Peritoneal dialysis (PD): infectious complications

AKA: peritonitis, exit site infection (ESI), tunnel infection (TI), catheter infection

Infectious complications in pediatric peritoneal dialysis patients

Overview

  • Infectious complications are the most common cause of hospitalization among dialysis patients, regardless of modality
    • Rates of hospitalization for infection have improved over time in the PD population
    • Infection-related deaths are about 2x more common in PD compared to
    • Infection is the most common cause of modality failure

Prevention

  • Intraoperative measures (“insertion bundle”)
    • Lateral/downward orientation of exit site
    • Preoperative prophylactic antibiotics
    • No sutures at exit site
  • If possible, allow catheter site to heal for at least 14 days before using
  • Training with qualified RN before PD initiated (“training bundle”) [ISPD guidelines]
    • 1:1 ratio of trainers to trainees
    • Include specific procedures for:
    • Home visit
    • Testing of training at first 1 month follow up
  • Monthly visits (“follow up bundle”)
    • Scoring of exit site per IPPN tool
    • Review training with the patient/family:
      • Hand hygiene
      • Exit site care
      • Aseptic connection technique
    • Ask about touch contaminations, breaks in aseptic technique
    • Training testing every 6 months
  • The more patients and dialysis centers can adhere to the above steps, the better the peritonitis rates
  • Indications for retraining of patients/caregivers:
    • After each episode of peritonitis and/or exit site/tunnel infection
    • Following prolonged hospitalization or period of time off PD
    • After a change in patient/caregiver dexterity, vision, or mental acuity
    • If equipment or catheter connection is changed

Additional prevention strategies

  • Pets should not be allowed in the room where PD is performed or where the PD supplies are kept
    • Pets (e.g., cats, rodents, birds) enjoy the warmth of the PD fluid heater and may try to play with the tubing
      • Damage may occur when the patient is asleep and easily goes unnoticed, increasing risk of zoonotic infections
  • Avoidance/treatment of hypokalemia may reduce peritonitis risk
  • Minimizing use of H2-receptor antagonists (e.g., famotidine) may reduce the risk of enteric peritonitis
    • However, switching to proton pump inhibitor (PPI) is not indicated for this reason given the other side effects of PPIs (e.g., ↑ risk of C. difficile infection)

Prophylaxis

Peritonitis prophylaxis

Antifungal and antibacterial regimens based on indication. Antibiotics should be given 30-60 minutes prior to the procedure. The abdomen should be emptied of fluid before any procedure involving the abdomen or pelvis.

Indication Antimicrobial
Risk factors for fungal peritonitis
  • High baseline rate of fungal peritonitis in PD unit
  • Gastrostomy tube placement
  • *Recent antibiotic use
  • Nystatin enteral 10,000 U/kg (max 500,000 U)
  • Fluconazole enteral/IV 3-6 mg/kg (max 200 mg/dose) q24-48h
Touch contamination
  • Instillation of PD fluid after disconnection of system
  • Disconnection during PD
  • Cefazolin IP 125 mg/L
  • If colonized with MRSA: vancomycin IP 25 mg/L
Use culture result to guide subsequent therapy
Invasive dental procedures
  • Manipulation of gingival tissue or of the periapical region (root) of teeth
  • Perforation of the gingival tissue
  • †Routine dental cleanings
 		Single dose of:
  • Amoxicillin enteral 50 mg/kg (max 2000 mg)
  • Ampicillin IV/IM 50 mg/kg (max 2000 mg)
  • Cefazolin IV 25 mg/kg (max 1000 mg)
  • Ceftriaxone IV/IM 50 mg/kg (max 1000 mg)
  • Clindamycin enteral 20 mg/kg (max 600 mg)
  • Clarithromycin enteral 15 mg/kg (max 500 mg)
  • Azithromycin enteral 15 mg/kg (max 500 mg)
High risk gastrointestinal (GI) procedures
  • E.g., esophageal stricture dilation, treatment of varices, colonoscopy, ERCP, gastrostomy placement
 		Single dose of:
  • Cefazolin IV 25 mg/kg (max 2000 mg)
  • Clindamycin IV 10 mg/kg (max 600 mg)
  • If high risk for MRSA, vancomycin IV 10 mg/kg (max 1000 mg)
Other GI or genitourinary (GU) procedures
  • Cefoxitin/cefotetan IV 30-40 mg/kg (max 2000 mg) x1 dose
    • Alternatives:
  • Cefazolin IV 25 mg/kg (max 2000 mg) plus metronidazole IV 10 mg/kg (max 1000 mg)
  • Clindamycin IV 10 mg/kg (max 600 mg) plus aztreonam IV 30 mg/kg (max 2000 mg)
  • *Some centers will start fungal peritonitis prophylaxis after any antibiotic administration, including single-dose prophylactic antibiotics. While pediatric data is not very robust, the adult data is compelling and the adult guidelines specifically recommend this practice. This is typically continued for 7 days after the last dose of antibiotic. Some centers will also use chronic antifungal prophylaxis in the setting of chronic antibiotic use (e.g., UTI or asplenia prophylaxis).
  • †Some centers will prescribe antibiotic prophylaxis (± *antifungal prophylaxis) with any "routine" dental cleanings as it is not always possible to anticipate the degree of "invasiveness" of the procedure ahead of time.

Presentation

  • Abdominal pain
  • Fever
  • Chills
  • Vomiting
  • Cloudy effluent
    • If yellow/green (bilious) or brown (feculent), evaluate for bowel perforation (i.e., enteric peritonitis/“surgical” peritonitis)
      • Suspicious for bowel perforation even without visible particulate matter

Noninfectious causes of cloudy effluent

Cause Notes
Chemical peritonitis May have neutrophil (PMN) or eosinophil predominance
Can be caused by icodextrin
Dialysate eosinophilia/eosinophilic peritonitis Consider if eosinophils >10%, especially with negative cultures
Specimen taken from 'dry' abdomen Macrophage/monocyte predominance
Hemoperitoneum May be caused by retrograde menstruation, endometriosis
Malignancy Lymphoma or peritoneal metastases
Fibrin May have had recent surgery, trauma, peritonitis
Triglycerides Milky white appearance
Caused by lymphatic obstruction, acute pancreatitis, calcium channel blockers

Diagnostic workup

  • Evaluate for exit site and tunnel infection
  • Collect dialysate sample
    • Should have collection protocol in place at institution
    • Ideally, use first cloudy bag or manual drain (e.g., at end of cycle #1)
    • Deliver to lab within 6 hours of collection
    • Do not freeze sample
      • May transport on ice for immediate delivery
      • For delayed delivery, refrigerate but do not freeze sample
  • Peritoneal fluid cell count
    • Empiric diagnosis of peritonitis
      • WBC >100/mm³ and ≥50% neutrophils (polymorphonuclear cells, “PMNs”)
        • If obtained after a shortened (<2 hour) dwell, 50% PMNs is suspicious for peritonitis even if WBC count is ≤100/mm³
          • If result is equivocal, can repeat with a 2 hour dwell
  • Gram stain & culture
    • Increase culture sensitivity to ~95% by obtaining ≥50 mL sample for centrifugation
      • Alternatively, 20-30 mL of unspun sample can be injected into 3-4 blood culture bottles (~80% sensitive)
    • Most cultures become positive within 24 hours
      • If still negative after 3-5 days but clinical picture is suspicious for peritonitis, may need to extend culture time to 7-9 days to identify slow growing bacteria and yeasts
  • The adult guidelines recommend 2 of 3 criteria be met:
    • Abdominal pain and/or cloudy effluent
    • WBC >100/mm³ and ≥50% neutrophils
    • Positive dialysis effluent culture
Algorithm for the collection of dialysis effluent for evaluation of suspected peritonitis in pediatric patients on peritoneal dialysis
Suspected peritonitis
Yes
No
Currently dwelling?
Infuse† ≥80% fill volume for 1-2* hours
Successful
(or if 2nd attempt)
Unsuccessful

Send 4 mL for cell count
(or 1-2 mL if small volume collected)

Send remaining sample (50 mL) for gram stain and culture

After ≥1* hour dwell, disconnect and collect‡ ≥54 mL
No
(repeat only once)
Yes
Resistance
with draw?
Unsuccessful
Successful
(or if 2nd attempt)
Collect‡ ≥54 mL
Troubleshoot catheter occlusion/ malposition

*2 hour dwell is ideal (↑ likelihood of positive culture), but ≥1 hour acceptable - helps to simplify collection procedure for patients and in emergency settings.

†If dialysate is unavailable (e.g., in ED), may dwell 0.9% normal saline (NS). For NS, infuse a fill
volume of 80 mL or ≥80% of the fill volume, whichever is less. NS is readily available in 10 mL flushes in bedside cart.

‡Collect sample directly from the PD catheter using a Luer lock syringe; if on a cycler, collecting
the sample from the drain bag can dilute the sample because of the presence of priming
fluid. Collect the sample as soon as cloudy fluid is noted to ↑ likelihood of positive culture.

Additional labs

  • Consider triglyceride level (in the dialysate effluent ± blood) if suspicious for chylous ascites (chyloperitoneum)
  • Peripheral blood culture(s) if septic or on immunosuppression
  • Consider dialysate effluent amylase level if concerned for bowel perforation

Imaging

  • Abdominal X-ray is not usually indicated
    • Free air (pneumoperitoneum) is common in PD patients: air can move into the abdomen via the catheter during exchanges
  • CT may identify abdominal pathology if hemodynamic instability, requiring ICU admission

Assess for exit site/tunnel infection

  • Evaluate exit site for swelling/induration, crusting, redness/erythema, tenderness/pain with palpation

Exit site scoring system

0
Score
1 		2
Swelling None Exit only
(<0.5 cm) 		Including part of/entire tunnel
Crust/eschar None <0.5 cm >0.5 cm
Redness/erythema None <0.5 cm >0.5 cm
Tenderness/pain with palpation* None Slight/mild Severe
Drainage/eschar None Serous Purulent
  • *Tenderness tends to be generalized, less often associated with rebound.
  • Exit site infection:
    • Score of 2+ with a known organism
    • Score of 4+ regardless of whether
  • Tunnel site infection:
    • Score of 6+
  • Unfortunately, interobserver agreement for non-negative findings is poor (~60%), even with experienced staff
    • Consider using the adult definition:
      • Exit site infection: purulent drainage with/without erythema
      • Tunnel infection: erythema, tenderness, and fluid collections (can be confirmed on ultrasound) along the tunnel

Microbiology

  • ~40% gram-positive
    • Most commonly Staph epidermidis
  • ~20-25% gram-negative
    • Most commonly Pseudomonas
  • ~2% fungal
  • 25-30% culture-negative

Peritonitis treatment

Principles

  • Initiate antifungal prophylaxis (PO or IV) while on antibiotics to minimize risk of fungal peritonitis
  • Intraperitoneal (IP) antibiotics are typically dosed continuously in pediatrics
    • Loading dose is allowed to dwell for 3-6 hours, followed by continuous cycles of dialysis at a lower maintenance

Indications for hospitalization

  • Fever, sepsis, hypotension
  • Significant abdominal pain
  • If unable to perform PD at home

Empiric therapy

  • Start broad-spectrum empiric intraperitoneal (IP) antibiotics as soon as possible
    • Cefepime monotherapy is usually 1st line for empiric treatment
      • If unavailable, combination of:
        • Gram-positive coverage with 1st generation cephalosporin (e.g., cefazolin) or vancomycin, AND
        • Gran-negative coverage with 3rd generation cephalosporin (e.g., ceftazidime) or aminoglycoside (typically gentamicin)
        • Examples:
      • If high rates of MRSA, may also use vancomycin empirically
      • Regimen should be specific to institutions and tailored to the regional prevalence of organisms
Gram-positive culture
MSSA
MRSA
Enterococcus
Other
• Cefazolin

• May add PO rifampin if poor response

Duration: 2-3 weeks
• Vancomycin (clindamycin if allergic)

• May add PO rifampin if poor response

Duration: 2-3 weeks
• PO amoxicillin if susceptible to ampicillin (vancomycin if resistant)

• VRE: daptomycin

or PO linezolid

Duration: 2-3 weeks
• Treat based on susceptibilities

• Narrow as able

Duration: 2 weeks
Streptococcus
Cefazolin (vancomycin if resistant)

Duration: 2 weeks
Stop empiric antibiotics

Gram-negative culture
Pseudomonas
Acinetobacter
Carbapenem-resistant Enterobacterales (CRE)
Other*
Ceftazidime, cefepime, meropenem, or PO ciprofloxacin

Duration: 3 weeks
No
Yes
• ID consult

• Treat based on susceptibilities

Duration: 2 weeks
Cefazolin or ceftazidime

Duration: 2 weeks
Stenotrophomonas maltophilia
PO/IV TMP-SMX

Duration: 3 weeks
Cefepime, ceftazidime,

or meropenem

Duration: 3 weeks
• Amikacin or colistin

AND

• Ampicillin-sulbactam (high dose)

Duration: 3 weeks
Carbapenem-resistant Acinetobacter baumanni (CRAB)?
AmpC ß-lactamase producing organisms

(Enterobacter cloacae, Klebsiella aerogenes, Citrobacter freundii)
Cefepime

(meropenem or PO ciprofloxacin if resistant)

Duration: 2 weeks
Extended-spectrum ß-lactamase producing Enterobacteriales (ESBL-E)**
Meropenem or PO ciprofloxacin (if susceptible)

Duration: 2 weeks
Note: all antibiotics listed in order of preference (if organism is susceptible)

*Organisms not otherwise specified in this algorithm, with no specified marker of resistance identified; this includes Serrata marcesens, in which produces a clinically significant amount of AmpC in <5% of strains.

**Any Enterobacterales not susceptible to a 3rd-generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime) should be presumed to be ESBL-E.
Stop empiric antibiotics

warning

AMP-C producing organisms can lead to clinical failure with early-generation cephalosporins, so resistance should be presumed even with in vitro susceptibility. Instead, recommend 4th generation cephalosporin (e.g., cefepime), quinolone or carbapenem. Organisms include the SPICE organisms: Serratia, Providencia, indole-positive Proteus, Citrobacter freundii and Enterobacter

Continuous intraperitoneal (IP) antibiotic dosing
Antibiotic Loading dose
(in 3-6 hour dwell) 		Maintenance dose
Cephalosporins
Cefepime, cefazolin, ceftazidime 500 mg/L 125 mg/L
Cefotaxime 500 mg/L 250 mg/L
Aminoglycosides*
Gentamicin, tobramycin 8 mg/L 4 mg/L
Amikacin 25 mg/L 12 mg/L
Glycopeptides
Vancomycin 1000 mg/L 25 mg/L
Penicillins*
Ampicillin
(IP form not recommended for Enterococcus) 		N/A 125 mg/L
Quinolones
Ciprofloxacin 50 mg/L 25 mg/L
Others
Aztreonam 1000 mg/L 250 mg/L
Clindamycin 300 mg/L 150 mg/L
Imipenem-cilastin 250 mg/L 50 mg/L
Antifungals
Fluconazole N/A 6-12 mg/kg q24-48h
(max 400 mg/day)
  • *Do not mix aminoglycosides and penicillins (e.g., ampicillin) together in the dialysate as they are not compatible; aminoglycosides can be mixed with cephalosporins.

Intermittent intraperitoneal (IP) antibiotic dosing
Antibiotic Dose*
Cephalosporins
Cefepime 15 mg/kg
Cefazolin 20 mg/kg
Cefotaxime 30 mg/kg
Ceftazidime 20 mg/kg
Aminoglycosides
Gentamicin, tobramycin, netilmycin, amikacin Anuric: 0.6 mg/kg
Non-anuric: 0.75 mg/kg
Glycopeptides
Vancomycin 30 mg/kg x1, then
15 mg/kg every 3-5† days (when level <15 g/L)
  • *Given daily in the long dwell, unless specified.
  • †Every 2-4 days in patients with residual kidney function.

Intravenous (IV) and enteral antimicrobial dosing
Antibiotic Dose
Enteral antibiotics
Metronidazole (enteral) 10 mg/kg 3 times daily
(max 1200 mg/day)
Rifampin (enteral) 5-10 mg/kg 2 times daily
(max 600 mg/day
Linezolid (enteral)* <5 years: 10 mg/kg 3 times daily
5-100 years: 10 mg/kg 2 times daily
≥12 years: 600 mg 2 times daily
Antifungals
Fluconazole (IV or enteral) 6-12 mg/kg 2 times daily
(max 400 mg/day
Caspofungin (IV) 70 mg/m²/day (max 70 mg) x1 day, then
50 mg/m²/day (max 50 mg/day)
  • *Linezolid can cause marrow suppression if used >14 days; monitor CBC

Pseudomonas peritonitis

  • If accompanied by exit site infection, catheter removal is recommended
  • If a fluoroquinolone is used, ciprofloxacin is preferred given the limited antipseudomonal activity of moxifloxacin

Culture-negative peritonitis

  • Presents multiple challenges
    • Difficult to target therapy
      • Can have a non-infectious etiology
    • Unable to use pathogen, which may provide clues as to the underlying etiology, to guide reeducation of patient and care providers
  • After 3 days:
    • If using aminoglycoside as empiric therapy it is recommended that after 72 hours of treatment the aminoglycoside be discontinued and ceftazidime be initiated (favorable side effect profile)
    • If culture still negative, repeat cell count
    • If no clinical improvement, request special culture to test for unusual organisms (mycobacteria, nocardia, filamentous fungus, and other fastidious bacteria)

Fungal peritonitis

  • High rates of treatment failure and mortality
  • Fungal elements on Gram stain should prompt treatment and catheter removal
  • Early catheter removal is recommended even based on the gram stain alone

Treatment duration

  • Gram-positive
    • Staph
      • MSSA/MRSA: 3 weeks
      • Coagulase negative Staph (CONS): 2 weeks
    • Enterococcus (including VRE): 2-3 weeks
      • Adult guidelines recommend 3 weeks
    • Streptococcus: 2 weeks
    • Corynebacterium: 2 weeks
  • Gram-negative
    • E. coli, Klebsiella: 2 weeks
      • Resistant to third generation cephalosporins: 3 weeks
    • Enterobacter, Citrobacter, Serratia, Proteus, Acinetobacter: 2-3 weeks
    • Pseudomonas, Stenotrophomonas maltophilia: 3 weeks
  • Culture-negative: 2 weeks

Relapsing peritonitis

  • Recurrence of peritonitis (with same organism) within 4 weeks of completion of antibiotics for the previous episode of peritonitis
    • Occurs in 10-20% of cases
  • Start with empiric therapy
    • Ensure that previous organism is covered
      • Avoid using cefazolin monotherapy even if prior organism was susceptible
        • Also need to cover for the possibility of a new organism
  • Consider catheter removal
    • First relapse if coagulase-negative Staph (CoNS)
    • Second relapse

Adjunctive therapies

  • If significant abdominal discomfort, consider lower fill volumes for 24-48 hours
  • Heparin often required for fibrinolysis (250-1000 U/L)
  • Evaluate IgG levels and consider IVIG
    • Particularly in patients with recurrent/refractory peritonitis or severe infections (sepsis)

Peritonitis outcomes

  • ~75% will resolve with antimicrobial therapy
  • ~60% require hospitalization
    • More frequent in gram-negative > fungal > gram-positive > polymicrobial > culture-negative
  • ~18% require catheter removal
    • 6% temporarily
    • 12% permanently (transitioned to
      )
      • More frequent in fungal >>> polymicrobial > gram-negative

Exit site / tunnel infection treatment

Enteral antibiotics used in exit site and tunnel infections

Antibiotic Dose Frequency
Amoxicillin 10-20 mg/kg/day
(max 1000 mg/dose) 		daily
Cephalexin 10-20 mg/kg/day
(max 1000 mg/dose) 		daily or divided 2 times daily
Ciprofloxacin 10-15 mg/kg/day
(max 500 mg/dose) 		daily
Clarithromycin 7.5 mg/kg/day
(max 500 mg/dose) 		daily or divided 2 times daily
Clindamycin 10 mg/kg
(max 600 mg/dose) 		3 times daily
Dicloxacillin <40 kg: 25-50 mg/kg
≥40 kg: 125-500 mg
(max 500 mg/dose) 		4 times daily
Erythromycin
(as base) 		30-50 mg/kg/day
(max 500 mg/dose) 		divided 3 or 4 times daily
Fluconazole 6 mg/kg
(max 400 mg/dose) 		q24-48h
Levofloxacin 10 mg/kg
(max 500 mg/dose on day 1,
then max 250 mg/dose) 		q48h
Linezolid <12 years: 10 mg/kg
(max 600 mg/dose)
≥12 years: 600 mg/dose 		<5 years: 3 times daily
≥5 years: 2 times daily
Metronidazole 10 mg/kg
(max 500 mg/dose) 		3 times daily
*Rifampin† 10-20 mg/kg/day
(max 600 mg/dose) 		divided 2 times daily
Trimethoprim-sulfamethoxazole
(TMP-SMX) 		‡5-10 mg/kg
(max 80 mg/dose) 		daily
  • *Should not be used routinely in areas where TB is endemic.
  • †Rifampin should not be used as monotherapy.
  • ‡TMP-SMX dosing based on TMP component

Catheter removal

  • Priority is saving the peritoneal membrane
  • Indications for catheter removal
    • After 5 days, if no clinical improvement the catheter should be removed
      • Removal is not mandatory if the white cell count is decreasing toward normal by this time
      • Includes culture-negative peritonitis
    • If fungal peritonitis, remove catheter immediately
    • Refractory peritonitis and/or exit site/tunnel infection
    • Peritonitis with concurrent exit site/tunnel infection with same organisms
      • Particularly if Staph aureus or Pseudomonas, but not for coagulase-negative Staph
    • Relapsing peritonitis
      • First relapse if coagulase-negative Staph (CoNS)
      • Second relapse
  • Continue antibiotics for at least 2 weeks after catheter is removed
  • PD catheter can generally be replaced after 2 or more weeks if infection has resolved
    • Simultaneous removal and replacement can be acceptable in relapsing bacterial peritonitis or for repeatedly relapsing/refractory exit site/tunnel infections (including Pseudomonas)
      • Only after the effluent has cleared (WBC <100/mm³)
    • In the case of mycobacterial peritonitis, wait at least 6 weeks to replace the catheter
    • In the meantime, will require placement of a HD catheter for