Infections in PD Prevention and Management

Peritonitis a cause of… Peritoneal membrane damage Hospitalization and pain Catheter loss Technique failure Death

Peritonitis: cells in effluent

Peritonitis: Infiltration

Pathogen Pathway

Tunnel Infection

Complications of Peritonitis Temporary loss of UF Increased protein losses Catheter loss Adhesions Sclerosing encapsulating peritonitis Transfer to HD Death

Peritonitis DEFINITION 1. Signs and symptoms 2. Cloudy fluid - >100 wbc/ml; >50%N 3. Identification of organism Two of three required for diagnosis RELAPSING PERITONITIS Another episode of peritonitis caused by the same genus/species within 4 weeks of completing antibiotic course

Cell count, with differential Peritonitis Diagnosis Cloudy fluid +/- abdominal pain +/- fever Dialysate effluent should be obtained for laboratory evaluation (>4 hrs’ dwell time): Culture Cell count, with differential Gram Stain Confirmation WBC count >100/mm3 , of which 50% are polymorphonuclear neutrophils (PMN), is confirmation of microbial-induced peritonitis

Clinical Course in CAPD Peritonitis Introduction of bacteria into peritoneum Bacteria Peritoneal wall Multiply ASYMPTOMATIC FOR 24 - 48 HRS Shed into PD fluid Abdo pain + Cloudy fluid = peritonitis

Micro-Organisms Causing Peritonitis Harwell PDI 1997;17:586-594

Routes of Peritoneal Infection Exchange procedure Haematogenous Titaneum/transfer set Pericatheter Transcolonic

Sources of Peritonitis, % Harwell PDI 1997 Contamination 41 Catheter related 23 Enteric injury 11 Perioperative 6 Diarrhoea/UTI 4 Sepsis 1 Unknown 14

Peritonitis - Yset Systems P risk % (Maiorca Lancet 1983) Y-set first by Buoncristianti 1980 Long Y with disinfectant Flush before fill Proliferation of disconnect systems standard Y set Months

CAPD vs APD

Initial assessment Symptoms: cloudy fluid and abdominal pain Do cell count/differential Gram stain and culture - on initial drainage Initiate empiric therapy Choice of final therapy should always be guided by antibiotic sensitivities

Gram Staining A gram stain is positive in 9-40% of peritonitis episodes When positive it is predictive of eventual culture results in 85% of cases It is particularly useful in early recognition of fungal peritonitis through revealing presence of yeast If on initial evaluation, a gram stain is +ve, a single antibiotic with activity against gram +ve organisms should be started Identification of a single organism on Gram stain does not preclude the presence of other organisms in lesser concentrations Finding gram +ve cocci and gram-negative rods together may indicate perforated abdominal viscous

Possible Causes of Culture Negative Peritonitis Culture methods of low sensitivity used – the culture techniques for PD effluent is specialized Culture volumes are too small Causative organism requires specialised culture media Cultures are taken from patients on antibiotic treatment The symptoms and signs are not due to infectious agents

Cloudy Effluent: Cellular Causes – Increased PMN Infectious causes Intraperitoneal visceral inflammation (eg, cholecystitis, appendicitis, bowel ischemia or obstruction) Juxtaperitoneal visceral inflammation (eg, pancreatitis, splenic infarction, abscess) Endotoxin-contaminated PD fluid Drug associated (eg amphotericin, vancomycin)

Cloudy Effluent: Cellular Causes – Increased Eosinophils Allergic reaction to constituent of dialysis system (e.g., sterilant, plasticizer) Drug associated (eg, vancomycin, streptokinase) Air-induced peritoneal irritation Blood-induced peritoneal irritation (e.g., retrograde menstruation)

Cloudy Effluent: Cellular Causes – Increased RBC Reproductive: Retrograde menstruation, Ovulation, Ectopic pregnancy Cyst rupture (ovarian or hepatic) Peritoneal adhesion formation Strenuous exercise Catheter-associated trauma Post-procedure: laparoscopy, colonoscopy Encapsulating peritoneal sclerosis Anticoagulation therapy Acute or chronic pancreatitis Post radiation

Lessons Organisms suggest causation: Outcomes depend on: S. Epidermis = touch contamination S. Aureus = catheter infection Outcomes depend on: Causative organisms and severity - Gram negative >> S. Aureus >> S. Epidermidis Associated conditions and severity Peritonitis + tunnel >> Peritonitis + ESI Peritonitis + ESI >> Peritonitis

Causative Organisms Bunke et al, KI 52:524-529, 1997

Gram Positive Organisms Bunke et al, KI 52:524-529, 1997

Organisms and Outcomes Bunke et al, KI 52:524-529, 1997

% of all episodes (without ESI/TI) Outcomes of Peritonitis Bunke, et al., KI 1997 % of all episodes (without ESI/TI)

*p<0.05 vs baseline for all times Time Course of UF After Peritonitis Ates, et al., PDI 20;2000:220-226 *p<0.05 vs baseline for all times

Prevention of Peritonitis Due to Contamination Disconnect systems Careful training Patient selection Assessment of home environment

Exit Site Infections - Prevention Staph aureus ESI occurs mainly in nasal carriers Incidence can be reduced by treating with mupirocin (M) (M) can be given intranasally twice daily x 5 days each month, or Applied (M) to exit site intermittently or daily as part of exit site care

S aureus CAPD related infections are associated with nasal carriage S. aureus episodes/year Data from Lye et al, 1994 Nasal carriage defined as min of 2 of 3 NC +ve

Effect of S aureus prophylaxis on prevention of S aureus peritonitis S aureus peritonitis/year Perez-Fontan Mupirocin Study Group Bernardini Thodis

Exit site/Tunnel and Outcomes Bunke et al, KI 52:524-529, 1997

Exit site/Tunnel and Outcomes Bunke et al, KI 52:524-529, 1997

Exit site/Tunnel and Outcomes Bunke et al, KI 52:524-529, 1997

Tunnel Ultrasonography Vychytil et al, AJKD 33:722-27, 1999 Indications Exit site infection (S. Aureus) Follow up of tunnel infection Peritonitis with exit site infection Recurrent/persistent peritonitis No indications Routine screening Search for foci in absence of ESI Peritonitis without ESI Tunnel pain with no other signs or symptoms

Peritonitis Rates Prevention is a realistic goal. Proof: Japan 1:45 to 1:60 patient/months Taiwan 1:35 to 1:45 patient/months Europe 1:26 to 1:38 patient/months Singapore 1:28 patient/months Mexico 1:24 to 1:26 patient/months

Peritonitis Rates 50% of patients account for 90% of infections Crabtree et al, ASAIO 45:574-80, 1999; Golper et al AJKD 28:428-36, 1996 50% of patients account for 90% of infections Patients with one infection episode are more likely to have another than those with none Most “repeat offenders” develop their infection early in the course of therapy: The earlier in dialysis history an infection develops, the more infection prone the patient continues to be. A high risk period for ESI/TI is in the 12 months post implant.

S. Aureus Nasal Carriage JASN 7:2403-8, 1996 Multicenter study in 9 European countries 1144 CAPD patients screened 267 (23%) carriers of S.Aureus (2 +ve swabs) JASN 9:669-76, 1998 Single center prospective 76 patients cultured monthly for 3 years One positive culture in 65.8% of all patients, 73% of diabetics, 72% of immunosuppressive Rx, 59% of others

Carriers State and Infection Vychytil et al, JASN 9:669-676, 1998

Staph Aureus Prophylaxis Bernardini et al, AJKD 27:695-700, 1996

EXIT SITE INFECTION (ESI) DEFINITIONS Acute ESI - purulent exit site drainage Additional features include redness, tenderness, edema and granulation tissue

Chronic Exit Site Infection ESI is chronic if it persists > 4 weeks Often there is crusting or scabbing Exuberant tissue, pus, redness With therapy improvement; epithelium spreads over granulation

Tunnel Infection Redness, edema and/or tenderness over the subcutaneous tunnel Often, there is associated ESI but some cases are occult May need ultrasound to diagnose

Exit Site Management Antibiotics Intensified local care Local debridement

Exit Site Management Local Debridement or Exteriorisation of cuff Can involve shaving external catheter cuff or revising tunnel Results are variable and many prefer catheter removal

Exit Site Infection PREVENTION Staph aureus ESI occurs mainly in nasal carriers Incidence can be reduced by treating with mupirocin (M) M can be given intranasally twice daily x 5 days each month Some apply M to exit site intermittently or daily as part of exit site care

Summary Keys to low infection rates include: Experienced personnel and careful training Minimize use of manual spike systems Continuous monitoring of infection rates and organisms Protocols for prevention, such as exit site mupirocin for S. aureus

Infectious Complications Predictable and Preventable!