1. Current Issues in PD Peritonitis

2. Baxter Healthcare Objectives Participants Will Review  Current Issues Related to Peritonitis  Current Treatment Recommendations  Prophylactic Antibiotic Recommendations

3. Baxter Healthcare Incidence and Impact Incidence Incidence 1 Approximately 1:24 patient months (US) 1:48 (Japan) Results center - dependent Peritonitis Causes 2,3... Hospitalization Catheter Loss Technique Failure Increased Albumin Losses Ultrafiltration Failure Increased Risk of Death 1. 1. Keane, 2000 2. 2. Burrows and Prowant, 1998 3. 3. Piraino, 1998

4. Baxter Healthcare Psychosocial 16% Peritonitis 25% Other Medical 9% Inadequate Dialysis 20% Catheter Related 30% Baxter 1999 Internal Data Causes of Dropout from PD

5. Baxter Healthcare Causes Of Peritonitis  55-80% - Gram Positives Skin Organisms/Touch Contamination Staph Epi, Staph Aureus, Streptococcus  17 - 30% - Gram Negatives Bowel Leak, Water Contamination Proteus, E-Coli, Klebsiella, Enterobacter, Acinetobacter, Pseudomonas  2-10% - Fungal Infections Candida Albicans primarily Brunier, 1995

6. Baxter Healthcare Organisms and Outcomes Bunke et al, KI 52:524-529, 1997

7. Baxter Healthcare Identifying Peritonitis  Key Findings - cloudy effluent, abdominal pain and/or fever  Diagnosis - 2 of the following 3   Symptoms of peritoneal inflammation; (fever, pain, chills, nausea, tenderness)   Cloudy fluid with WBC > 100/mm 3 ; 50% polymorphonuclear neutrophils (PMN)   Identification of organism on gram stain or culture Burrows L, Prowant 1998

8. Baxter Healthcare

9. Relapsing Peritonitis  Definition Peritonitis caused by the same genus/species responsible for the immediately preceding episode, within 4 weeks of completion of the antibiotic course Burrows and Prowant, 1998

10. Baxter Healthcare Causes of a Cloudy Bag  Infectious peritonitis  Peritoneal fluid eosinophilia  Blood tinged dialysate (ovulation, menstruation, etc...)  Fibrin filaments  Chylous peritoneum  Intra-abdominal pathologies (Cholecystitis, appendicitis, pancreatitis, salpingitis, malignancy etc…)  Diarrhea

11. Baxter Healthcare Portals of Entry of Organisms  Exogenous - Transluminal  Exogenous - Periluminal  Endogenous  Procedure related

12. Baxter Healthcare Changes in Transport with Peritonitis  Decreased net ultrafiltration  Increased peritoneal fluid absorption  Increased small solute transport  Increased protein clearances

13. Baxter Healthcare Portals of Entry of Organisms  Exogenous - Transluminal Bag exchange Bag exchange Transfer set exchange Transfer set exchange Injection of drugs Injection of drugs Accidental disconnection Accidental disconnection Defective PD System Defective PD System Contaminated PD fluid Contaminated PD fluid

14. Baxter Healthcare Portals of Entry of Organisms  Exogenous - Periluminal Exit site infection Exit site infection Cuff and tunnel infection Cuff and tunnel infection  Endogenous Enteric/abdominal source Enteric/abdominal source Bacteremia Bacteremia Gynecologic in origin Gynecologic in origin  Procedure related

15. Baxter Healthcare Portals of Entry of Organisms  Exogenous - Transluminal  Exogenous - Periluminal  Endogenous  Procedure related Colonoscopy Colonoscopy Endoscopy Endoscopy Dental procedures Dental procedures

16. Baxter Healthcare Portals of Entry of Organisms  Exogenous - Transluminal S. Epidermidis, Acinetobacter S. Epidermidis, Acinetobacter  Exogenous - Periluminal S. Epidermidis, S. Aureus, Pseudomonas, Yeast S. Epidermidis, S. Aureus, Pseudomonas, Yeast  Endogenous Enteric: gram negative, anaerobes Enteric: gram negative, anaerobes Bacteremia: Strep, anaerobes Bacteremia: Strep, anaerobes Gynecologic: Lactobacillus, yeast Gynecologic: Lactobacillus, yeast

17. Calculating Peritonitis Rates One (1) episode per Patient Months at Risk  Determine months at risk number of patient days /30.42 (avg.days per mo) number of patient days /30.42 (avg.days per mo) ex: 92 days X 30 pts = 2760/ 30.42 = 90.73 months ex: 92 days X 30 pts = 2760/ 30.42 = 90.73 months  Divide months at risk by episodes within time period ex: 90.73/ 3 = 1: 30.24 mos. Episodes per Patient Year  Determine years at risk number of patient days / 365 ex: 92 days X 30 patients = 2760/ 365 = 7.56 years  Divide number of reported episodes by years at risk ex: 3/ 7.56 = 0.40 episodes per year Burrows and Prowant, 1998

18. Baxter Healthcare Culture Considerations “Appropriate” Effluent for Culture   First Cloudy effluent best odds of positive culture   Collect large volume (  50 mL)   If turbid, length of dwell irrelevant   Collect 2 nd sample if clear or unsure CAPD – > 4 hour dwell APD –  2* hour dwell Keane, 2000 * changed from ‘96

19. Baxter Healthcare Laboratory Procedure  To improve recovery of organisms Wash specimen with sterile saline Treat with antibiotic removing resin  Concentrate sample (> 50 mL) Centrifuge (3000g x 15 min) Re-suspend sediment in 3-5 mL of NSS Inoculate into blood culture medium Culture Considerations Keane, 2000

20. Baxter Healthcare  Limited Vancomycin Use  Limited Aminoglycoside Use if RRF*  Empiric Therapy  Culture-Sensitive Therapy Current Treatment Recommendations Keane, 2000 * changed from ‘96

21. Baxter Healthcare  Vanco empiric Rx of choice  Vanco WAS empiric Rx of choice  ~ 14% of enterococci in larger university hospitals now Vanco resistant !  Vanco resistance often associated with resistance to other agents, such as penicillin or aminoglycosides  Resistance WAS confined to enterococci, spreading to other organisms  If Vanco resistance reaches MRSA..... No Rx available Vancomycin Resistance Keane, 2000

22. Baxter Healthcare  Vanco should ONLY be used to Rx Methicillin Resistant Staph Aureus (MRSA) Beta-lactam resistant organisms SERIOUS SERIOUS Gm+ infection if allergic to other Rx C. difficile enterocolitis unresponsive to metronidazole Limited Use of Vancomycin Keane, 2000

23. Baxter Healthcare  Broad spectrum (gram pos & gram neg)  Was  Was Empiric Rx of choice in combination with 1 st generation cephalosporins regardless of residual urine output  was  Regardless of residual urine output, was part of recommended Rx regime for enterococci (+) staph aureus (+) pseudomonas/xanthomonas (-)   Generics Amikacin Gentamicin Netilmicin Tobramycin Aminoglycosides Keane, 1996

24. Baxter Healthcare Aminoglycosides and Residual Renal Function (RRF) Shemin et al, 1999

25. Baxter Healthcare  Ceftazadime with RRF (> 100 mL/day) 3 rd generation cephalosporin Broad Spectrum  Replace Aminoglycosides with RRF In Empiric recommendations In Gram Negative Recommendations Aminoglycoside Alternative* Keane, 2000 * Change from 1996

26. Baxter Healthcare  Gram + associated with peritonitis Coagulase negative staphylococcus Coagulase negative staphylococcus Corynebacterium Corynebacterium Micrococcus Micrococcus Staph aureus Staph aureus Staph epidermidis Staph epidermidis Streptococci (includes entercocci) Streptococci (includes entercocci)  Gram - associated with peritonitis Escherichia coli Escherichia coli Klebseilla Klebseilla Pseudomonas/ Xanthomonas Pseudomonas/ Xanthomonas Serratia Serratia Actinobacter Actinobacter Neisseria Neisseria Proteus Mirabilis Proteus Mirabilis Some of the Common Bacterial Causes of Peritonitis Troidle, 1998

27. Baxter Healthcare 1996  Cephalosporin (1 st gen) and  Aminoglycoside Treating Empirically (before culture results) 2000  If No RRF (< 100 mL) Cephalosporin (1 st gen) Cephalosporin (1 st gen)and Ceftazidime Ceftazidimeor Aminoglycoside Aminoglycoside  If RRF (> 100 mL) Cephalosporin (1 st gen) Cephalosporin (1 st gen)and Ceftazidime Ceftazidime Keane et al, 1996 Keane et al, 2000

28. Baxter Healthcare 1996  DC Cephalosporin and continue and continue   AminoglycosideADD   Ampicillin Treating Gram Positive Enterococci 2000  DC Cephalosporin and  DC Ceftazidime ADD  Ampicillin If Ampicillin- resistant Vanco or Clindamycin Vanco or Clindamycin If Vanco – resistant Quinupristin or Dalfopristin Quinupristin or Dalfopristin Consider Adding Aminoglycosides Aminoglycosides Keane et al, 1996 Keane et al, 2000

29. Baxter Healthcare 1996  DC Aminoglycosides and continue  Cephalosporin ADD ADD  Rifampin Treating Gram Positive Staph Aureus 2000 DC Ceftazidime DC Ceftazidimeor DC Aminoglycosides DC Aminoglycosides and continue Cephalosporin (1 st gen) Cephalosporin (1 st gen)ADD Rifampin Rifampin If MRSA, ADD Vanco or Clindamycin Vanco or Clindamycin Keane et al, 1996 Keane et al, 2000

30. Baxter Healthcare 1996  DC Aminoglycosides and continue  Cephalosporin Treating Other Gram Positives 2000 DC Ceftazidime DC Ceftazidimeor DC Aminoglycosides DC Aminoglycosides and continue Cephalosporin (1 st gen) Cephalosporin (1 st gen) If MRSE, ADD Vanco or Clindamycin Vanco or Clindamycin Keane et al, 1996 Keane et al, 2000

31. Baxter Healthcare 1996  Adjust Antibiotics to Sensitivity Patterns Treating Single Gram Negatives 2000  Adjust Antibiotics to Sensitivity Patterns Keane et al, 1996 Keane et al, 2000

32. Baxter Healthcare 1996  DC Cephalosporin and continue  Aminoglycosides ADD another  Pseudomonas Agent Ceftazadime Ceftazadime Piperacillin Piperacillin Ciprofloxacin Ciprofloxacin Aztreonam Aztreonam Imipenemem Imipenemem Sulfamethoxazole Sulfamethoxazole Treating Pseudomonas/ Xanthomonas 2000  Con’t Ceftazidime and  If RRF > 100 mL, ADD Ciprofloxacin po --or- Ciprofloxacin po --or- Piperacillin IV –or— Piperacillin IV –or— Sulfamethoxazole –or— Sulfamethoxazole –or— Aztreonam IP Aztreonam IP  If RRF < 100 mL, Con’t Aminoglycosides Con’t Aminoglycosides Keane et al, 1996 Keane et al, 2000

33. Baxter Healthcare 1996  Con’t Cephalosporin and  Con’t Aminoglycoside and  Add Metronidazole and  Consider Surgical Intervention Treating Multiple Gram Negatives and/or Anaerobes 2000  Con’t Cephalosporin and  Con’t Ceftazadime and  Add Metronidazole and  Consider Surgical Intervention Keane et al, 1996 Keane et al, 2000

34. Baxter Healthcare 1996  DC Cephalosporins and  DC Aminoglycoside and Start  Flucytosine and  Fluconazole Treating Yeast 2000  DC Cephalosporins and  DC Aminoglycoside and Start  Flucytosine and  Fluconazole if resistant organism Consider Itraconozole Consider Itraconozole Keane et al, 1996 Keane et al, 2000

35. Baxter Healthcare  Exit Site Mupirocin (may use intranasally)  Before procedures that may seed, such as dental work dental work colonoscopy colonoscopy  Pre-catheter or post technique failure Cephalosporin –1 st generation Cephalosporin –1 st generation Avoid Vancomycin Avoid Vancomycin Prophylactic Antibiotic Use Keane et al, 2000

36. Baxter Healthcare  Adults Only Pediatric Recommendations Forthcoming  Avoid Aminoglycosides If residual urine output > 100 mL/ day Ceftazidime instead (3 rd generation cephalosporin)   min dwell for APD culture to 2 hr (was 1 hr) CAPD remains  4 hr  May consider oral treatment in APD ONLY in UNCOMPLICATED coag neg staph Peritonitis Update 2000 --- Summary of Changes (from ’96) Keane et al, 2000

37. Baxter Healthcare  Treat uncomplicated gram Neg for 21-day min Previously 14-day minimum  Multiple Gram Negative Infections Remove catheter even if improvement noted  TB Peritonitis Add Pyridoxine 100mg/ day Remove catheter in ALL cases Peritonitis Update 2000 --- Summary of Changes (con’t) Keane et al, 2000

38. Baxter Healthcare  Preventative Treatments Amoxicillin 2gm – “Reasonable” pre-dental 1-2 day course of cephalosporins after technique break (altho no data available) Exit Site Mupirocin for ALL PD patients except those with Cruz catheters   Eliminates need for nasal swabs   Mupirocin preferred over Rifampin  Catheter Reinsertion may be done immediately ONLY if peritonitis 2  Biofilm formation (typically due to coag neg staph) Tunnel involvement (typically due to SA relapse) WBC’s in effluent < 100  L w/ antibiotics Peritonitis Update 2000 --- Summary of Changes (con’t) Keane et al, 2000

39. Baxter Healthcare References 1. 1.Keane W, Baile G, Boeschoten E, Gokal R, Golper T, Holmes C, Kawaguchi Y, Piraino B, Riella M, and Vas S. Adult Peritoneal Dialysis Related Treatment Recommendations: 2000 Update, Perit Dial Int, 20:396-411, 2000 2. 2.Piraino B, Prevention of peritonitis, Perit Dial Int, 18: 244-246, 2000 3. 3.Burrows L, Prowant : Peritoneal Dialysis, in Contemporary Nephrology Nursing, edited by Janel Parker, Pitman NJ, ANNA, 603-659, 1998 4. 4.Brunier, G. Peritonitis in Patients on Peritoneal Dialysis. A Review of Pathophysiology and Treatment. ANNA Journal, 22:575-585, 1995 5. 5.Keane W., Alexander S, Baile G, Boeschoten E, Gokal R, Golper T, Holmes C, Huang CC, Kawaguchi Y, Piraino B, Riella M, Schaefer F, and Vas S. Peritoneal dialysis related treatment recommendations: 1996 Update, Perit Dial Int, 16: 557-573, 1996 6. 6.Bunke CM, Brier M, Golper T, Outcomes of single organism peritonitis in peritoneal dialysis: Gram negatives versus gram positives in the network 9 peritonitis study, Kidney Int, 52: 524-529, 1997 7. 7.Shemin D, Maax D, Pierre DS, Kahn SI, Cgazan JA. Effects of aminoglycoside use on residual renal function in peritoneal dialysis, Am J Kidney Dis; 34:14-20, 1999 8. 8.Troidle L, Gorban-Brennan, N, Kliger A, Finkelstein F. Differing Outcomes of Gram– Positive and Gram-Negative Peritonitis. Am J. Kidney Dis, 32: 623-628, 1998