Le Peritoniti Flavia Caputo Although incidence rates of peritonitis have decreased substantially with the introduction of the flush-before-fill double-bag principle, and the emergence of improved connection systems… Peritonitis is still the achilles'heel of peritoneal dialysis Mactier R.Perit Dial Int. 2009 May-Jun;29 Peritoneal dialysis-associated peritonitis is the most common acute complication of PD and has been the main cause of technique failure. Repetitive or protracted peritonitis episodes can also damage the peritoneal membrane Selgas R, Paiva A, Bajo MA et al. Adv Perit Dial1998; 14: • Drop-out per peritonite: 5-10% dei paz/anno • Peritonite come causa di drop-out: 25- 40% • Degenza ospedaliera: 5 giorni/anno paziente in trattamento • Mortalità per peritonite 2-12% Peritonitis as a Cause of Peritoneal Dialysis Technique Failure Study Study period Study patients Initial Cure Tecniques failure due to peritonitis Kavanagh et al., 2004 1992-2002 All adult patients in Scotland 75% 42.6% Johnson et al., 2007 2004-2006 All centers in Australia 78% (2006 data 29% only) Davenport, 2009 2002-2003 All centers in London, UK >80% in only 2 of 12 units 41.7% Mactier R.Perit Dial Int. 2009 May-Jun;29 Factors affecting the rate of tecnique failure: Kavanagh D, Prescott GJ, Mactier RA, NDT 2004;19 ISPD Standards and Guidelines Committee Minutes from the June 2008 Meeting in Istanbul In attendance: Beth Piraino, Frank Schaefer, Judith Bernardini, Edwina Brown, Flavia Caputo, Ana Figueiredo, Valerie Price Update on Peritoneal Dialysis- Related Infections, 2005 published in 2005 in PDI The committee felt that it was time to renew this guideline. It will be split into two parts. One will deal with Management of PD Related Infections. This guideline will be led by Dr Philip Li who has been invited to join the committee to ensure good communication. He will put together the working group. Projected complete date: 2010. Addendum: The part of the previous guideline on Prevention of PD related infections will be separated and developed as a position paper as there is not enough rigorous data for guidelines. This will be led by Dr Beth Piraino. Dr Philip Li and Dr Beth Piraino will sit on each other’s work groups. Projected time table: completion by mid 2009. The committee will be asked if they agree with this approach. First published in 1983 and revised in 1989, 1993, 1996 and 1995 2010 UPDATE Every program should regularly monitor infection rates, at a minimum, on a yearly basis Opinion ISPD 2010 The center’s peritonitis rate should be no more than 1 episode every 18 months (0,67/year) Reported <0,29-0,23/year GOAL to achieve! Cheng YL, AJKD 2002, 40. 373 Choi KH, Perit Dial Int 2004: 424-432 ISPD 2010 Methods 1. As rates • Interval in months between episodes • Episodes for year 2. As percentage of patients per period of time who are peritonitis free 3. As median peritonitis rate for the program Study (Ref. Study period Study location Patients (n) PD system Months between Comparison of Peritonitis Rates in Peritoneal Dialysis episodes of peritonitis (PD) Patients Using the Double-Bag Disconnect System Monteon et al., 1998 (8) - Multicenter; 147 Mexico CAPD 24,8 Li et al., 1999 (9) - Multicenter; 120 Hong Kong CAPD 33,5 Huang et al., 2001 (10) 1993–2001 Single center; Taipei, Taiwan 117 CAPD 45,4 Katz et al., 2001 (11) 1998-1999 Single center; Soweto, South Africa 84 CAPiva a 45 D 27,9 Kavanagh et al., 2004 (5) 1999–2002 All centers in Scotland 1205 APD/CAPD 19,2 Johnson et al., 2007 (6 2006 All centers in Australia 2021 APD/CAPD 21,0 Davenport, 2009 (7) 2002–2003 All centers in London, 863 at the end of 2002 APD/CAPD 15,9 Esperienza del nostro centro Dati 2008 Dati 2009 o 25 episodi in 66 pazienti 20 episodi in 58 pazienti o 1 episodio ogni 25mesi/pz 1 episodio ogni 29 mesi/pz o 0.48 ep/anno/paz. 0.41 ep/anno/paz. ISPD 2010 PERITONITIS Peritoneal dialysis patients presenting with cloud effluent OR abdominal pain Diagnosis is confirmed with cell count and culture 1. ≥100 WBC per mcL with more than 50% PMN 2. Positive culture EVIDENCE ISPD 2010 Differential Diagnosis of Cloud Effluent • Culture positive infectious peritonitis • Infectious peritonitis with sterile cultures • Chemical peritonitis • Eosinophilia of the effluent • Hemoperitoneum • Malignacy (rare) • Chylous effluent (rare) ISPD 2010 Culture-negative peritonitis should not be greater than 20% episodes Standard culture technique is the use of blood- culture bottles, but culturing the sediment after centrifuting 50 mL of effluent is ideal for low culture-negative results EVIDENCE ISPD Guidelines 2010 In the ideal situation less than 10% rate of culture negative peritonitis ISPD 2010 The correct microbiological culturing of peritoneal effluent is of the most importance to establish the microrganism responsible. Centrifugation 50 mLperitoneal effluent at 3000g for 15 minutes…… Rapidblood-culturetechniques (BACTEC) Other novel diagnostic techniques: •Leukocyte esterase reagent strip •PCR withRNA/DNA assays •MMP 9 Vie di contaminazione e microrganismi Intraluminale Staf.epidermidis e altri SCN Staf.aureo (30/40%) Strept.Viridans Periluminale Staf. Epidermidis e altri SCN Staf.Aureo (20/30%) Pseudomonas Difterici Funghi Colibacilli (25/30%) Transmurale Enterobacteriacee Anaerobi Ematogena Streptococchi (5/10%) M. Tubercolosis Ascendente Lactobacilli (2/5%) Funghi Vie di contaminazione ESOGENA ENDOGENA • Endoluminale 30-40% • Periluminale 20-30% Adeguato training • Transmurale 25-30% • Ascendente 2-5% • Ematogena/Linfatica 5-10% La via endoluminale rappresenta il 40% delle vie di contaminazione Cause: Manovre non corrette nel cambio sacca Tramite rotture della sacca o del set Disconnessioni accidentali Soluzioni non sterili Per tale motivo il TRAININGriveste un ruolo fondamentale nella prevenzione delle peritoniti L’utilizzo di un incrementato metodo di training è positivamente associato con il migliorato esito del paziente (evidence) New directions in dialysis patient training Nephrol. Nurs. 2004 Il metodo di training influenza il rischio di infezioni in dialisi peritoneale (Evidence). EXIT SITE CARE ISPD GUIDELINES/RECOMMENDATIONS 2005 Le PD nurses sono fondamentali per un programma di dialisi peritoneale con un basso indice di infezioni: •- Lavaggio mani •- Exit site care •- Uso della mascherina •- Diagnosi precoce dell’ESI e del TI Vie di contaminazione ESOGENA • Endoluminale Adeguato training 30-40% • Periluminale ESI / TI 20-30% Carriage Staph. Aureus ENDOGENA • Transmurale 25-30% • Ascendente 2-5% • Ematogena/Linfatica 5-10% Peritonitis associated with exit-site infections B. Piraino- AJKD, 1996 Mupirocin Gentamicin Pvalue Episodes per year at risk P. aerginosa 0.04 0 0.14 Other Gram negative 0.11 0.02 0.02 0 0.03 NS Fungal 0.04 0.03 NS Peritonitis overall 0.52 0.34 0.03 S. aureus Bernardini J, Piraino B, JASN 2005 Feb; 16: 539-45 Gentamicin cream applied daily to the exit-site compared to mupirocin significantly reduced EXITE SITE INFECTION (57%) PERITONITIS (35%) Bernardini J, Piraino B JASN 2005 Feb; 16: 539-45 Vie di contaminazione ESOGENA • Endoluminale Adeguato training 30-40% • Periluminale Exit-siteinfection 20-30% CarriageStaph. Aureus ENDOGENA • Transmurale Profilassi antibiotica Evitare la stipsi 25-30% • Ascendente 2-5% • Ematogena/Linfatica 5-10% ISPD 2005 There is an association between both severe constipation and enteritis and peritonitis due to enteric organisms EVIDENCE ISPD Guidelines 2005 Possibly, peritonitis results from trans migration of micro-organisms across the bowel wall. • Hipomotility disorders • Drugs contributing (oral iron, oral calcium, some analgesics) • Hypokaliemia Training: AVOIDANCE OF CONSTIPATION! Vie di contaminazione ESOGENA • Endoluminale Adeguato training 30-40% • Periluminale Exit-siteinfection 20-30% CarriageStaph. Aureus ENDOGENA • Transmurale Profilassi antibiotica Evitare la stipsi 25-30% • Ascendente Fistole vaginali Ascessi 2-5% retroperitoneali • Ematogena/Linfatica 5-10% Vie di contaminazione ESOGENA ENDOGENA • Endoluminale Adeguato training 30-40% • Periluminale Exit-siteinfection 20-30% CarriageStaph. Aureus antibiotica • Transmurale Profilassi Evitare la stipsi 25-30% • Ascendente Fistole vaginali Ascessi 2-5% retroperitoneali • Ematogena/Linfatica Profilassi antibiotica 5-10% in corso di procedure invasive ISPD 2005 Invasive procedure may infrequently cause peritonitis in PD patients EVIDENCE ISPD Guidelines 2005 Antibiotic prophylaxis: • A single oral dose of amoxicillin (2g) 2 hours before extensive dental procedure Opinion • Patients undergoing colonscopy with polypectomy: Ampicillin 1g+ a single dose of an aminoglycoside ± metroinidazole, given i.v. just prior the procedure Opinion N.B. The abdomen must be empty of fluid prior to all procedures involved the abdomen or pelvis (colonsopy, renal transplantation, endometrialbiopsy) Opinion A Bundle of Care of Clinical Practice to Reduce Risk of peritonitis Prevention of touch contamination • Disconnect systems • Prompt antibiotic therapy after accidental contamination • Hand disinfection technique • Patient training and periodic retraining • Patient selection Prevention of catheter-related infection • Prophylactic antibiotics at the time of catheter insertion • Downward facing exit-site • Immobilization of newly inserted catheter • Prophylactic antibiotics to the exit-site Prevention of enteric infection • Avoid constipation • Empty peritoneal cavity and prophylactic antibiotics before endoscopy, colonscopy, or barium enema Prevention of recurrent peritonitis • Adequate antibiotics therapy for 2-3 weeks • Removal of the catheter if Staphylococcus aereus or Pseudomonas exit-site or tunnel infection • Oral nystatin during courses of antibiotics Mactier R.Perit Dial Int. 2009 May-Jun;29 ISPD 2010 Therapy should be initiated as soon is possible, after appropriate microbiological specimen have been obtained PATIENT EDUCATIONAL ISPD 2010 PATIENT EDUCATIONAL • Immediately report cloudy effluent, abdominal pain and/or fever to PD unit • Save drained cloudy dialysate and bring to clinic • Treatment will be adding intraperitoneal antibiotics for up to 3 weeks • Report worsening symptoms or persistent cloudiness to PD unit • Schedule retraining for technique issues 6-8 hours 0-6 hours Start intraperitoneal antibiotics as soon as possible Allow to dwell for at least 6 hours Ensure gram-positive and gram negative coverage* Base selection on historical patient and center sensitivity patterns as available Gram-positive coverage Either Vancomycin** or first generation cephalosporin Gram-negative coverage Either third-generation cephalosporin*** or aminoglycoside Determine and prescribe ongoing antibiotic treatment Ensure follow-up arrangements are clear or patient admitted Await sensitivity results INITIAL MANAGEMENT OF PERITONITIS ISPD 2010 • La dose I.P. è sempre preferibile. IP administration has the advantage of a high concentration of the antibiotic at the site of infection. The major drawback is that injection of the antibiotic into the bag induces a potential extra risk of contamination. In this regard, once-daily IP administration has great advantages. Intravenous administration should be avoided as this can destroy vascular access possibilities that are precious for the future Van Biesen W, Vanholder R, Lameire N. Perit Dial Int 2000; 20 Intraperitoneal Drug Therapy: An Advantage. Chaudhary Curr Clin Pharmacol. 2010 ISPD 2010 THERAPY 1. EMPIRIC THERAPY (therapy is initiated prior to knowledge of causative organism) The Committee reccomends center-specific selection of empiric therapy, dependent on the local history of sensitivies of organismies causing peritonitis The protocol must cover all serious pathogens that are likely to be present Opinion ISPD 2010 EMPIRIC THERAPY Cefazolin Or Vancomicin and Ceftazidime Or Gentamicin N.B. Short-term use of aminoglycoside therapy appears to be safe for the risk of ototoxicity (once day dose) ISPD 2010 Monotherapy: • Imipenem/cilastatin 50mg = cefazolin+ceftazidime Leung CB, Szeto CC, Chow KM, Perit Dial Int, 24: 440, 2004 • Cefepime 2 g = vancomycin+netilmicin Wong KM, Chan CY, Cheung CY, Leung SH, Am J Kidney Dis 38: 127, 2001 • Quinolones (oral levofloxacin 250 mg/day or perfloxacin 400 mg/day) = aminoglycosides for gramnegative Yeung SM, Walker SE, Tailor SA, Perit Dial Int 18: 371, 2004 ISPD 2010 ISPD 2010 Other gram-positive organisms including coagulase negative staphylococcus on culture Continue gram-positive coverage based on sensitivities Stop gram-negative coverage Assess clinical improvement, repeat dialysis effluent cell count and culture at days 3-5 - Symptoms resolved - Bags clear Clinical improvement - Continue antibiotics; - duration of therapy: 14 days No clinical improvement - Re-culture & evaluate* Re-evaluate for exit-site or occult tunnel infection, intraabdominal abscess, catheter colonization etc Peritonitis with exit-site or tunnel infection consider catheter removal** Duration of therapy: 21 days No clinical improvement by 5 days on appropriate antibiotics, remove catheter ISPD 2010 Staphylococcus aureus on culture Continue gram-positive coverage based on sensitivities* Stop gram-negative coverage, assess exit site again If methicillin resistant, adjust coverage to vancomycin or teicoplanin** Add rifampin 600 mg/day orally (in single or split dose) for 5 to 7 days (450 mg/day if BW < 50 kg) Assess clinical improvement , repeat dialysis effluent cell count and culture at days 3-5 - Symptoms resolved - Bags clear Clinical improvement - Continue antibiotics - Duration of therapy 21 days No clinical improvement - Re-culture & evaluate Re-evaluate for exit-site or occult tunnel infection, intraabdominal abscess, catheter colonization etc Peritonitis with exit-site or tunnel infection may prove to be refractory**** and the catheter must be removed. Allow a minimum rest period of 3 weeks before re-initiating PD***** No clinical improvement by 5 days on appropriate antibiotics, remove catheter ISPD 2010 ISPD 2010 Enterococcus/Streptococcus on culture Discontinue starting antibiotics* Start continuous ampicillin 125 mg/L each bag; consider adding aminoglycoside for enterococcus** If ampicillin resistant, start vancomycin; If vancomycin resistant enterococcus, consider quinupristin/dalfopristin, daptomycin, or linezolid Assess clinical improvement, repeat dialysis effluent cell count and culture at days 3-5 - Symptoms resolved - Bags clear Clinical improvement - Continue antibiotics; duration of therapy: 14 days (streptococcus) 21 days (enterococcus) No clinical improvement - Re-culture & evaluate Re-evaluate for exit-site or occult tunnel infection, intraabdominal abscess, catheter colonization etc Peritonitis with exit-site or tunnel infection consider catheter removal*** Duration of therapy: 21 days No clinical improvement by 5 days on appropriate antibiotics, remove catheter ISPD 2010 Culture negative on day 1 & 2 Continue initial therapy Day 3: Culture still negative Clinical assessment Repeat PD Fluid white cell count and differential Infection resolving Patient improvement clinically Continue initial therapy for 14 days Infection not resolving Special culture technique for unusual causes (e.g. viral, mycoplasma, mycobacteria, legionella). Consider fungi Now culture positive Adjust therapy according to sensitivity patterns Duration of therapy based on organism identified Still culture negative Clinical improvement Continue antibiotic Duration of therapy: 14 days No clinical improvement after 5 days Remove catheter* Continue antibiotics for at least 14 days ISPD 2010 Pseudomonas species on culture Without catheter infection (exit-site/tunnel) Give 2 different antibiotics acting in different ways that organism is sensitive to eg oral quinolone, ceftazidime, cefapime, tobramycin, piperacillin Assess clinical improvement, repeat dialysis effluent cell count and culture at days 3-5: Symptoms resolved - Bags clear Clinical improvement - Continue antibiotics; - duration of therapy: 21 days No clinical improvement - Re-culture & evaluate - Consider changing antibiotics No clinical improvement by 5 days on appropriate antibiotics, remove catheter With catheter infection(exitsite/tunnel) current or prior to peritonitis Catheter removal* Continue oral and/or systemic antibiotics for at least two weeks ISPD 2010 Single gram-negative organism on cultureon culture* Other E. coli proteus, klebsiellaetc Stenotrophomonas Adjust antibiotics to sensitivity pattern Cephalosporin (ceftazidime or cefepime) may be indicated Treat with 2 drugs with differing mechanisms based on sensitivity pattern (trimethoprim / sulphamethoxazole is preferred) Assess clinical improvement , repeat dialysis effluent cell count and culture at days 3-5: Symptoms resolved - Bags clear Clinical improvement - Continue antibiotics; - Minimum 21 day treatment Assess clinical improvement at days 3-5: - Symptoms resolved - Bags clear No clinical improvement by 5 days on appropriate antibiotics - remove catheter Clinical improvement - Continue antibiotics: 21- 28 days treatment ISPD 2010 Polymicrobial peritonitis: days 1-3 Multiple gram-negative organisms or mixed gram negative/gram positive - consider GI problem Change therapy to metronidazole in conjunction with ampicillin, ceftazidime or aminoglycoside Obtain urgent surgical assessment In case of laparotomy indicating intraabdominal pathology/abscess, remove catheter* Continue antibiotics – 14 days Multiple gram-positive organisms - Touch contamination - Consider catheter infection Continue therapy based on sensitivities Without exit site or tunnel infection – continue antibiotics Duration of therapy minimum 21 days based on clinical response With exit site or tunnel infection, remove catheter* The Commette feels that the minimum of therapy for peritonitis is 2 weeks, athough for more severe infections, 3 weeks is reccomended Opinion After initiation of antibiotic treatment clinical improvement shoud be present in the first 72 hours ISPD 2010 Fungal peritonitis Fungal peritonitis is a serious complication leading to death in 25% or more episodes ,should be strongly suspected after recent antibiotic treatment for bacterial peritonitis. Catheter removal is indicated immediately after fungi are identified by microscopy or culture EVIDENCE ISPD 2010 PERITONITIS DUE TO MYCOBACTERIA Mycobacteria are an infrequent cause of peritonitis but can be difficult to diagnose. When under clinical consideration, special attention must be paid to culture techniques. Treatment requires multiple drugs EVIDENCE They can be caused by Mycobacterium tuberculosis or nontuberculosis mycobacteria, such as M. fortuitum, M. avium, M. abscessus and M. chelonei ISPD 2010 Terminology of peritonitis Terminology for peritonitis • Recurrent: An episode that occurs within 4 weeks of completation of therapy for a prior episode but with a different organism • Relapsing: An episode that occurs within 4 weeks of completation of therapy for a prior episode with the same organism or one sterile episode • Repeat: An episode that occurs after 4 weeks of completation of therapy for a prior episode with the same organism • Refractory: Failure of the effluent to clear after 5 days of appropriate antibiotics • Catheter-related peritonitis: Peritonitis in conjunction with exit-site or tunnel infection with the same organism or one site sterile When calculating peritonitis rates, Relapsing episodes should not be counted as another peritonitis; while recurrent and repeat should be counted ISPD 2010 \ Indications for catheter removal: • Relapsing peritonitis • Refractory peritonitis • Fungal peritonitis • Refractory catheter infections The focus shoul be on preservation of the peritoneum rather than saving peritoneal catheter Opinion ISPD 2010 Catheter reinsertion A minimum period of 2-3 weeks between catheter removal and reinsertion of a new catheter is raccomanded, although some would reccomend later reinsertion in case of fungin peritonitis ISPD 2010 REFRACTORY PERITONITIS Refractory peritonitis, defined as failure to respond to appropriate antibiotics within 5 days, should be managed by removal of the catheter to protect the peritoneal membrane for future use ISPD 2010 OUTCOMES EVALUATION • • • • • • • • Collect data to include Date of culture, organism identified, drug therapy used Date infection resolved Recurrent organisms, date of drug therapy Method of interim renal replacement therapy Date of catheter removal Date of new catheter reinsertion Documentation of contributing factors – Break in technique, patient factors, exit-site infections, tunnel infections • Date of re-education/training • Enter data into catheter management database