1. Infectious Complications of PD: Peritonitis and Exit Site / Tunnel Infections Franz Schaefer Pediatric Nephrology Division Center for Pediatric and Adolescent Medicine University of Heidelberg, Germany Download Presentation at: www.pedpd.org

2. Reasons for Hospitalizations

3. Reasons for Change of Dialysis Modality* Percent NAPRTCS, 2006 * Other than transplantation

4. Causes of Death for Prevalent Pediatric PD Patients (2000-02) USRDS, 2004 Mortality per 1000 patient years at risk

5. www.peritonitis.org

6. Prevention of Peritonitis Catheter-related factors Prevention of exit-site and tunnel infections Direct tunnel downward or use swan-neck catheter Use double-cuff catheters Use exit-site mupirocin Timely replacement of the catheter for catheter-related peritonitis Contamination Experienced nursing personnel Avoidance of spiking technology Long training period Training protocols Antibiotic prophylaxis Preoperative antibiotics at catheter insertion Contamination at time of exchange Dialysate leak at catheter exit site Invasive procedures Exit site mupirocin Warady & Schaefer, In: Chap. 24, Pediatric Dialysis, 2004

7. Peritonitis: Diagnostic Criteria Cloudy effluent Dialysate WBC count >100/uL >50% polymorphonuclear leukocytes Positive culture

8. Peritonitis: Effluent Cloudiness

10. Peritonitis: Source of Infection Unknown: 70 % ! Episodes (%)

11. Spectrum of Causative Organisms Schaefer et al. Kidney Int 2007

12. Regional Distribution of Culture Results Schaefer et al. Kidney Int 2007

13. If the patient presents with: -No fever -Mild or no abdominal pain -No risk factors for severe infection Glycopeptide (e.g. vancomycin, 30 mg/l cont. or 30 mg/kg q.5-7 days) and Ceftazidime (continuous 125 mg/L or 250 mg/L o.d.) If any of the following is present: -Fever, severe abdominal pain, age <2 yrs -History of MRSA infection or carrier -Recent or current exit site/tunnel infection Initiate empiric therapy Peritoneal effluent evaluation Cell count and differential Gram stain, culture Cloudy effluent Cefazolin (250/125 mg/l) and Ceftazidime (continuous 125 mg/L or 250 mg/L o.d.) EMPIRIC THERAPY

14. Cefazolin/ Ceftazidime Glycopeptide/ Ceftazidime Any Treatment Gram positive5/90 (5.6%)4/129 (3.1%)9/219 (4.1%) Gram negative4/56 (7.1%)12/65 (18.5%) 16/121 (13.2%) * Culture negative4/92 (4.4%)2/59 (3.4%)6/151 (4.0%) Any culture result13/238 (5.5%)18/253 (7.1%)31/491 (6.3%) Clinical Response Failure after 72h Empiric Antibiotic Treatment Warady et al. JASN 2007; 18:2172

15. Risk of Day 3 Clinical Response Failure Odds ratio (95% Cl)P Gram-negative causative organism 3.61 (1.73 - 7.54)P <0.001 Intermittent ceftazidime administration (only gram-negative) 6.65 (2.07 – 21.4)P <0.005 APD modality: 'dry day' vs. 'wet day' 2.53 (1.18 - 5.42)P <0.01 Exit site score >2 (only gram-positive) 5.46 (1.02 - 29.7)P <0.05 No effect: choice of empiric therapy, risk assignment

16. In vitro Resistance Predicts Empiric Therapy Failure Odds ratio 95% CI Gram-positive 16.3 1.5 - 180 Gram-negative 9.3 1.6 - 52

17. In vitro Sensitivities by Gram

18. Schaefer et al. Kidney Int 2007 In vitro Resistance Rates

19. Final Outcome Outcome PD Continued PD DiscontinuedTotal TemporaryPermanent Full functional recovery 42090429 (89%) Ultrafiltration problems 81716 (3.3%) Adhesions311115 (3.1%) Uncontrolled infection 011112 (2.5%) Secondary fungal peritonitis 0044(0.8%) General therapy failure 0066 (1.3%) Total431 (89%)12 (3%)39 (8%)482 (100%)

20. Outcome by Causative Organism Rate of successful outcome (%)

21. Risk of Incomplete Functional Recovery OR (95% CI)P Disease Severity Score day 3 3.68 (1.72 – 7.84)< 0.0005 Straight vs. curled catheter 2.70 (1.24 – 5.87)< 0.005 Exit-site score 1.34 (1.05 – 1.71)< 0.005 Pseudomonas on culture 3.57 (1.11 – 11.5)< 0.05 No effect: choice of empiric therapy, risk assignment

22. Monitor local staphylococcal methicillin, gram-negative ceftazidime resistance patterns Cefazolin OR Glycopeptide and Aminoglycoside OR (continuous) Ceftazidime Initiate empiric therapy Peritoneal effluent evaluation Cell count and differential Gram stain, culture Cloudy effluent Revised Guideline: Empiric Antibiotic Therapy

23. Revised Guideline: Modification for Culture Negative Episodes If improved clinically: Continue 1st generation cephalosporin or glycopeptide for 14 days Discontinue aminoglycoside after 3 days Add/continue ceftazidime after 3 days If not improved clinically: Remove catheter

24. Exit Site Infection

25. Diagnosis of Exit-Site Infection The diagnosis of a catheter exit-site infection should be made in the presence of a purulent discharge from the sinus tract or marked pericatheter swelling, redness and/or tenderness with or without a pathogenic organism cultured from the exit-site. Infectious symptoms should be rated according to an objective scoring system. GUIDELINE 14 Warady, Schaefer et al., Peritonitis Guidelines, PDI, 2000

26. Exit-Site Scoring System 0 Points 1 Point 2 Points SwellingnoExit only (<0.5 cm)Including part of or entire tunnel Crustno 0.5 cm Rednessno 0.5 cm Pain on pressurenoSlightSevere SecretionnoSerousPurulent Schaefer F. et al. J Am Soc Nephrol 10:136-145, 1999 a Infection should be assumed with a cumulative exit-site score of 4 or greater.

27. Causative Organisms at Exit Site % of 58 episodes

28. Therapy of Exit Site Infection Usually oral Usually upon culture results Grampositive usually penicillinase- resistant penicillin or cefalexin Length of therapy at least two weeks One-stage catheter replacement for refractory ESI

29. Exit-site infection rate0.340.02 Tunnel infection rate0.090.02 Peritonitis rate0.170 Nasal Carriers Noncarriers S.Aureus Infection Rate Luzar et al, NEJM, 1990

30. Nasal S.Aureus Decontamination Piraino B, J Am Soc Nephrol, 1998 S. aureus Peritonitis, Episodes / y

31. Options for Prevention of Exit-Site Infections

32. Topical S.Aureus Prophylaxis

33. Warady et al., Peritonitis Guidelines, PDI 2000 Prophylaxis for S. Aureus Nasal Carriage Nasal culture every 2-4 wks until positive x 1 or negative x 6 If negative x 6: no prophylaxis needed If positive Mupirocin intra-nasally BID x 5 d every 4 wks Mupirocin at exit site daily

34. Exit Site and Peritonitis Exit site co-colonization is associated with 2-fold likelihood of peritonitis treatment failure 3-fold likelihood of catheter exchange Schaefer et al. Kidney Int 2007 Pseudomonas peritonitis is associated with Use of saline or soap for cleansing (p twice per week (p<0.005) Use of exit site mupirocin (p<0.005) Being United States resident (OR 2.95, p<0.01)

35. Indications for Catheter Removal Failure to respond to appropriate antibiotics within 5 days Fungal peritonitis Peritonitis with exit site/tunnel infection Recurrent peritonitis Chronic exit site infection

36. International Pediatric PD Network www.pedpd.org