1. Fungal Peritonitis (FP) Constantinos J. Stefanidis “P. and A. Kyriakou” Children’s Hospital Athens, Greece

2. Empiric diagnosis of peritonitis EffluentCloudy Cell count>100 /mm³ Differential>50% PMN Pain, fever and a positive dialysate culture are facultative features of peritonitis. Dialysate culture results are typically not available before 24 hours and are not helpful in initial clinical decision making. The criteria represent international consensus among adult and pediatric nephrologists. ISPD GUIDELINES/RECOMMENDATIONS

3. How frequent is FP? 1% of all episodes of peritonitis

4. Period: Sept. 2001 – Dec. 2004 Participating centers Patients Peritonitis Episodes 20 392550 http://www.peritonitis.org International Pediatric Peritonitis Registry

5. International Pediatric Peritonitis Registry (2001-2004) Sterile 30% Gram-positive species 44% Gram-negative species 24% Fungus (8) 1% http://www.peritonitis.org

6. Mid European Pediatric PD Study Group (1993-1998) Sterile 19% Gram-positive species 64% Gram-negative species 16% Fungus 1% Schaefer et al. JASN 1999

7. FP has a different clinical presentation? NO

8. Clinical presentation and causative organism * International Pediatric Peritonitis Registry 2001-2003

9. * Clinical presentation and causative organism

10. What treatment would you recommend? Treatment should be initiated with: Amphotericin B IV Loading dose: 1 mg/kg IV Maintenance: 1 mg/kg/day) IV or a combination of fluconazole: 3-6 mg/kg ip, iv or po q 24-48 hrs) flucytosine Loading dose: 50 mg/kg po Maintenance: 250-350 mg/kg /day ISPD Consensus Guidelines for the Treatment of Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis Perit Dial Intern 2000 http://www.peritonitis.org

11. NO The intraperitoneal administration is irritating the peritoneum and may result in severe abdominal pain. Should we use amphotericin B IP ?

12. ? 6 patients received fluconazole (per os or IV 5-7 mg/kg) followed by IP (75 mg/L) Amphotericin B was added when clinical sepsis was present. Eradication of the fungus was possible in the majority of cases Montane BS et al. Adv Perit Dial. 1998 Should we use amphotericin B IV as an initial treatment ?

13. The peritoneal penetration of amphotericin B with systemic administration is poor. Fluconazole has an excellent bioavailability and peritoneal penetration, and is currently the drug of choice for most Candida species. Ideally fungal susceptibilities should be obtained to help direct therapy. What is the therapy of choice ?

14. The recommended dose of fluconazole is the same for PO, IP or IV administration, since oral absorption of fluconazole is essentially complete, ISPD Consensus Guidelines for the Treatment of Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis Perit Dial Intern 2000 http://www.peritonitis.org Which route of administration of fluconazole would you advocate?

15. Choice of treatment Warady BA et al: a report of the NAPRTCS. Kidney Int 2000 Amphotericin B IV 30/42 Amphotericin B IP 11/42 Fluconazole 11/42 Flucytosine 13/42 >1 24/42 Nr of episodes

16. The duration of antifungal treatment following catheter removal should be 2 weeks or longer following complete resolution of the clinical symptoms of infection (or 4 - 6 weeks without catheter removal) How long we should treat FP?

17. In patients in whom the catheter is not removed initially, immediate catheter removal should take place if improvement does not occur within 3 days of treatment initiation. ISPD Consensus Guidelines for the Treatment of Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis Perit Dial Intern 2000 http://www.peritonitis.org When peritoneal dialysis catheter should be removed ? Early catheter removal is recommended.

18. To prevent: the high possibility of fungi to colonize the PD catheter and the dissemination of the infection despite drug therapy ISPD Consensus Guidelines for the Treatment of Peritonitis in Pediatric Patients Receiving Peritoneal Dialysis Perit Dial Intern 2000 http://www.peritonitis.org Why PD catheter should be removed?

19. Leonard MB al: a report of the NAPRTCS. Kidney Int 2001 Reasons for a change in dialysis modality Transition from PD to HD 20% of 997 pts Transition from HD to PD 21% of 388 pts January 1, 1992 and December 30, 1998

20. Catheter removal (in 90% of FP episodes) and successful therapy in 51 children with FP frequently resulted in preservation of the peritoneal membrane and continuation of PD. Warady BA et al: a report of the NAPRTCS. Kidney Int 2000 Is it possible to restart PD ?

21. Time of catheter removal following FP Warady BA et al: a report of the NAPRTCS. Kidney Int 2000 20818

22. Patient outcome 6 months after FP Warady BA et al: a report of the NAPRTCS. Kidney Int 2000

23. Two months after catheter removal When PD should be restarted?

24. Prior use of antibiotics to treat bacterial peritonitis or a catheter-related infection. Robitaille P et al: Perit Dial Int 1995 Lo WK et al Am J Kidney Dis 1996 Thodis E et al: Perit Dial Int 1998 Nearly 50% of children who developed fungal peritonitis, have no received antibiotics (for peritonitis, ESI, or other reason) prior to the peritoneal infection. Warady BA et al: a report of the NAPRTCS. Kidney Int 2000 What are the predisposing factors for the development of FP?

25. NO Murugasu B et al. Pediatr Nephrol 1991 Warady BA et al: a report of the NAPRTCS. Kidney Int 2000 Gastrostomy feeding is a predisposing factor for the development of FP?

26. Warady BA et al: a report of the NAPRTCS. Kidney Int 2000 Gastrostomy feeding is a predisposing factor for the development of FP?

27. Remains controversial, but is generally advocated In a pediatric study, oral nystatin (10 000 U/kg/day) was associated with a significant decrease in the risk of fungal peritonitis in patients receiving antibiotics Robitaille P et al: Perit Dial Int 1995 What is the role of antifungal prophylaxis in the setting of antibiotic therapy? ISPD GUIDELINES/RECOMMENDATIONS

28. How to prevent peritonitis? With a continuous quality initiative program Borg D et al Adv Perit Dial. 2003

29. How to prevent peritonitis? With the appropriate management of inadequate dialysis and malnutrition Hippocrates (460-377 BC) It is better to prevent than to treat

30. Messages to take home Fungal peritonitis is a rare complication of peritoneal dialysis ( it represents 1% of all episodes of peritonitis ) The optimal management is early catheter removal and the administration of a variety of anti-fungal agents The mortality rate is not high in the paediatric population Preservation of the peritoneal membrane and continuation of PD is feasible with early PD catheter removal and appropriate therapy