Spontan-bakterielle und sekundäre Peritonitis bei Patienten mit Leberzirrhose und Aszites

Zusammenfassung

Die Peritonitis stellt eine der häufigsten infektiösen Komplikationen beim Patienten mit Leberzirrhose und Aszites dar. In mehr als 95 % der Fälle tritt sie als spontan-bakterielle Peritonitis (SBP) als Folge der Translokation von Bakterien aus dem Darmlumen in die mesenterialen Lymphknoten mit nachfolgender systemischer Zirkulation auf. Identifizierte Risikofaktoren, die eine antibiotische Prophylaxe der SBP rechtfertigen, stellen eine vorausgegangene Episode einer SBP, das Auftreten einer gastrointestinalen Blutung und ein erniedrigtes Aszitesprotein in Verbindung mit Nieren- oder fortgeschrittener Leberinsuffizienz dar. Die Therapie der SBP ist ausschließlich konservativ und sollte unter Berücksichtigung individueller und nosokomialer Risikofaktoren für antimikrobielle Resistenzen empirisch mit Cephalosporinen der 3. Generation unter zusätz-licher Gabe von Albumin durchgeführt werden. Im Gegensatz zur SBP ist die sekundäre bakterielle Peritonitis ein deutlich selteneres ( < 5 % aller Fälle) und prognostisch ungünstigeres Krankheitsbild, das als Folge einer Hohlorganperforation oder eines entzündlichen oder ischämischen intraabdominellen Prozesses entsteht. Die Höhe der Neutrophilenkonzentration im Aszites sowie klinisch-chemische und mikrobiologische Untersuchungen im Aszites sind geeignet, den Verdacht auf eine sekundäre Peritonitis zu erhärten und sollten eine sofortige sorgfältige Abklärung inklusive abdomineller Computertomografie nach sich ziehen. Aufgrund der hohen Mortalität von 60 – 80 % sind bei der sekundär-bakteriellen Peritonitis ein Anaerobier-wirksames antibiotisches Therapieregime, eine zeitnahe chirurgische Versorgung und eine interdisziplinäre postoperative Betreuung der Patienten indiziert.

Abstract

Peritonitis is one of the most frequent infectious complications in patients with liver cirrhosis and ascites. In more than 95 % it occurs as spontaneous bacterial peritonitis (SBP) as a result of bacterial translocation from intestinal bacteria and bacterial products into mesenteric lymph nodes and subsequent systemic circulation. Identified risk factors that justify antibiotic prophylaxis for SBP include a prior episode of SBP, gastrointestinal haemorrhage and low ascitic fluid protein in combination with renal or advanced liver failure. SBP requires conservative therapy, which should be empirically performed using third-generation cephalosporins and adjunctive albumin therapy under consideration of individual and nosocomial risk factors for antimicrobial resistance. In contrast to SBP, secondary bacterial peritonitis is a rare ( < 5 % of all cases of peritonitis) and more unfavourable disease. It occurs as a result of hollow organ perforation or intra-abdominal inflammatory or ischaemic processes. Analysis of ascitic fluid may help substantiating the suspicion of secondary peritonitis and should entail a meticulous diagnostic work-up including abdominal computed tomography. Because of the high mortality rate (60 – 80 %) of secondary peritonitis antibiotic regimens with anti-anaerobic activity, prompt surgical treatment and interdisciplinary postoperative care are necessary to improve patient outcomes.

Schlüsselwörter

Peritonitis - Infektion - Leberversagen

Key words

peritonitis - infection - liver failure

• Literatur

• 1 Cazzaniga M, Dionigi E, Gobbo G et al. The systemic inflammatory response syndrome in cirrhotic patients: relationship with their in-hospital outcome. J Hepatol 2009; 51: 475-482
• 2 Wong F, Bernardi M, Balk R et al. Sepsis in cirrhosis: report on the 7^th meeting of the International Ascites Club. Gut 2005; 54: 718-725
• 3 Gomez F, Ruiz P, Schreiber AD. Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis. N Engl J Med 1994; 331: 1122-1128
• 4 Fiuza C, Salcedo M, Clemente G et al. In vivo neutrophil dysfunction in cirrhotic patients with advanced liver disease. J Infect Dis 2000; 182: 526-533
• 5 Lin C-Y, Tsai I-F, Ho Y-P et al. Endotoxemia contributes to the immune paralysis in patients with cirrhosis. J Hepatol 2007; 46: 816-826
• 6 Bruns T, Peter J, Hagel S et al. The augmented neutrophil respiratory burst in response to Escherichia coli is reduced in liver cirrhosis during infection. Clin Exp Immunol 2011; 164: 346-356
• 7 Borzio M, Salerno F, Piantoni L et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis 2001; 33: 41-48
• 8 Arvaniti V, D’Amico G, Fede G et al. Infections in Patients With Cirrhosis Increase Mortality Four-Fold and Should Be Used in Determining Prognosis. Gastroenterology 2010; 139: 1246.e5-1256.e5
• 9 Fleming KM, Aithal GP, Card TR et al. All-cause mortality in people with cirrhosis compared with the general population: a population-based cohort study. Liver Int 2011; [in press]
• 10 D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44: 217-231
• 11 Sersté T, Melot C, Francoz C et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology 2010; 52: 1017-1022
• 12 Bruns T, Sachse S, Straube E et al. Identification of bacterial DNA in neutrocytic and non-neutrocytic cirrhotic ascites by means of a multiplex polymerase chain reaction. Liver Int 2009; 29: 1206-1214
• 13 Bruns T, Peter J, Reuken PA et al. NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis. Liver Int 2011; [in press]
• 14 Chang CS, Yang SS, Kao CH et al. Small intestinal bacterial overgrowth versus antimicrobial capacity in patients with spontaneous bacterial peritonitis. Scand J Gastroenterol 2001; 36: 92-96
• 15 Chang CS, Chen GH, Lien HC et al. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology 1998; 28: 1187-1190
• 16 Scarpellini E, Valenza V, Gabrielli M et al. Intestinal permeability in cirrhotic patients with and without spontaneous bacterial peritonitis: is the ring closed?. Am J Gastroenterol 2010; 105: 323-327
• 17 Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F et al. Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding – an updated Cochrane review. Aliment Pharmacol Ther 2011; 34: 509-518
• 18 Runyon BA. Low-protein-concentration ascitic fluid is predisposed to spontaneous bacterial peritonitis. Gastroenterology 1986; 91: 1343-1346
• 19 García-Díaz M, Alcalde M, de Sande F et al. Low protein concentration in cirrhotic ascites is related to low ascitic concentrations of immunoglobulins G and A. Eur J Gastroenterol Hepatol 1995; 7: 963-969
• 20 Runyon BA, Morrissey RL, Hoefs JC et al. Opsonic activity of human ascitic fluid: a potentially important protective mechanism against spontaneous bacterial peritonitis. Hepatology 1985; 5: 634-637
• 21 Trikudanathan G, Israel J, Cappa J et al. Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients – a systematic review and meta-analysis. Int J Clin Pract 2011; 65: 674-678
• 22 Senzolo M, Cholongitas E, Burra P et al. beta-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. Liver Int 2009; 29: 1189-1193
• 23 Nischalke HD, Berger C, Aldenhoff K et al. Toll-like receptor (TLR) 2 promotor and intron 2 polymorphisms are associated with increased risk for spontaneous bacterial peritonitis in liver cirrhosis. J Hepatol 2011; 55 (05) 1010-1016
• 24 Appenrodt B, Grünhage F, Gentemann MG et al. Nucleotide-binding oligomerization domain containing 2 (NOD2) variants are genetic risk factors for death and spontaneous bacterial peritonitis in liver cirrhosis. Hepatology 2010; 51: 1327-1333
• 25 Bruns T, Reuken PA, Fischer J et al. Further evidence for the relevance of TLR2 gene variants in spontaneous bacterial peritonitis. J Hepatol 2011; [in press]
• 26 Guarner-Argente C, Sánchez E, Vidal S et al. Toll-like receptor 4 D299G polymorphism and the incidence of infections in cirrhotic patients. Aliment Pharmacol Ther 2010; 31: 1192-1199
• 27 Ginès P, Angeli P, Lenz K et al. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010; 53: 397-417
• 28 Gerbes AL, Gülberg V, Sauerbruch T et al. [German S 3-guideline “ascites, spontaneous bacterial peritonitis, hepatorenal syndrome”]. Z Gastroenterol 2011; 49: 749-779
• 29 Titó L, Rimola A, Ginès P et al. Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. Hepatology 1988; 8: 27-31
• 30 Ginés P, Rimola A, Planas R et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology 1990; 12: 716-724
• 31 Soriano G, Guarner C, Teixidó M et al. Selective intestinal decontamination prevents spontaneous bacterial peritonitis. Gastroenterology 1991; 100: 477-481
• 32 Singh N, Gayowski T, Yu VL et al. Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial. Ann Intern Med 1995; 122: 595-598
• 33 Rolachon A, Cordier L, Bacq Y et al. Ciprofloxacin and long-term prevention of spontaneous bacterial peritonitis: results of a prospective controlled trial. Hepatology 1995; 22: 1171-1174
• 34 Fernández J, Ruiz delArbol L, Gómez C et al. Norfloxacin vs. ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology 2006; 131: 1049-1056
• 35 Llach J, Rimola A, Navasa M et al. Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration. Hepatology 1992; 16: 724-727
• 36 Guarner C, Solà R, Soriano G et al. Risk of a first community-acquired spontaneous bacterial peritonitis in cirrhotics with low ascitic fluid protein levels. Gastroenterology 1999; 117: 414-419
• 37 Fernández J, Navasa M, Planas R et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology 2007; 133: 818-824
• 38 Terg R, Fassio E, Guevara M et al. Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study. J Hepatol 2008; 48: 774-779
• 39 Angeli P, Guarda S, Fasolato S et al. Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Aliment Pharmacol Ther 2006; 23: 75-84
• 40 Terg R, Cobas S, Fassio E et al. Oral ciprofloxacin after a short course of intravenous ciprofloxacin in the treatment of spontaneous bacterial peritonitis: results of a multicenter, randomized study. J Hepatol 2000; 33: 564-569
• 41 Navasa M, Follo A, Llovet JM et al. Randomized, comparative study of oral ofloxacin versus intravenous cefotaxime in spontaneous bacterial peritonitis. Gastroenterology 1996; 111: 1011-1017
• 42 Aparicio JR, Such J, Pascual S et al. Development of quinolone-resistant strains of Escherichia coli in stools of patients with cirrhosis undergoing norfloxacin prophylaxis: clinical consequences. J Hepatol 1999; 31: 277-283
• 43 Ortiz J, Vila MC, Soriano G et al. Infections caused by Escherichia coli resistant to norfloxacin in hospitalized cirrhotic patients. Hepatology 1999; 29: 1064-1069
• 44 Fernández J, Navasa M, Gómez J et al. Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatology 2002; 35: 140-148
• 45 Concepción M, Poca M, Gordillo J et al. Evolution Of Antibiotic Susceptibility Of Bacteria Causing Spontaneous Bacterial Peritonitis: A 9-Year Study (Abstract). J Hepatol 2011; 54 (Suppl. 01) 380-380
• 46 Cheong HS, Kang C-I, Lee JA et al. Clinical significance and outcome of nosocomial acquisition of spontaneous bacterial peritonitis in patients with liver cirrhosis. Clin Infect Dis 2009; 48: 1230-1236
• 47 Follo A, Llovet JM, Navasa M et al. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. Hepatology 1994; 20: 1495-1501
• 48 Sort P, Navasa M, Arroyo V et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999; 341: 403-409
• 49 Soriano G, Castellote J, Alvarez C et al. Secondary bacterial peritonitis in cirrhosis: a retrospective study of clinical and analytical characteristics, diagnosis and management. J Hepatol 2010; 52: 39-44
• 50 Akriviadis EA, Runyon BA. Utility of an algorithm in differentiating spontaneous from secondary bacterial peritonitis. Gastroenterology 1990; 98: 127-133
• 51 Runyon BA, Hoefs JC. Ascitic fluid analysis in the differentiation of spontaneous bacterial peritonitis from gastrointestinal tract perforation into ascitic fluid. Hepatology 1984; 4: 447-450
• 52 Wu SS, Lin OS, Chen YY et al. Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the differentiation of primary from secondary bacterial peritonitis with intestinal perforation. J Hepatol 2001; 34: 215-221
• 53 Hartl W, Kuppinger D, Vilsmaier M. Sekundäre Peritonitis. Zentralbl Chir 2011; 136: 11-17
• 54 Pacelli F, Doglietto GB, Alfieri S et al. Prognosis in intra-abdominal infections. Multivariate analysis on 60 patients. Arch Surg 1996; 131: 641-645
• 55 Wacha H, Hau T, Dittmer R. Peritonitis Study Group et al. Risk factors associated with intraabdominal infections: a prospective multicenter study. Langenbecks Arch Surg 1999; 384: 24-32
• 56 Ziser A, Plevak DJ, Wiesner RH et al. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Anesthesiology 1999; 90: 42-53
• 57 Teh SH, Nagorney DM, Stevens SR et al. Risk factors for mortality after surgery in patients with cirrhosis. Gastroenterology 2007; 132: 1261-1269
• 58 van Till JWO, van Veen SQ, van Ruler O et al. The innate immune response to secondary peritonitis. Shock 2007; 28: 504-517
• 59 Dunn DL, Barke RA, Ahrenholz DH et al. The adjuvant effect of peritoneal fluid in experimental peritonitis. Mechanism and clinical implications. Ann Surg 1984; 199: 37-43
• 60 Caralis PV, Sprung CL, Schiff ER. Secondary bacterial peritonitis in cirrhotic patients with ascites. South Med J 1984; 77: 579-583
• 61 Wong PF, Gilliam AD, Kumar S et al. Antibiotic regimens for secondary peritonitis of gastrointestinal origin in adults. Cochrane Database Syst Rev; 2005 CD004539
• 62 van Ruler O, Kiewiet JJS, van Ketel RJ et al. Initial microbial spectrum in severe secondary peritonitis and relevance for treatment. Eur J Clin Microbiol Infect Dis 2011; [in press]
• 63 Seguin P, Fédun Y, Laviolle B et al. Risk factors for multidrug-resistant bacteria in patients with post-operative peritonitis requiring intensive care. J Antimicrob Chemother 2010; 65: 342-346
• 64 de Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53: 762-768