Rifaximin – ein nicht resorbierbares Antibiotikum mit vielfältigen Anwendungsmöglichkeiten in der Gastroenterologie

Zusammenfassung

Seit 2 Jahren ist in Deutschland Rifaximin als darmselektives Breitbandantibiotikum zur Behandlung der durch nicht invasive enteropathogene Bakterien verursachten Reisediarrhö verfügbar. Aufgrund der guten Verträglichkeit und der hohen Wirksamkeit gegen darmpathogene Erreger wird ein hohes Zukunftspotenzial dieses seit mehr als 25 Jahren bekannten Arzneistoffs v. a. in weiteren Indikationsgebieten gesehen, die Gegenstand aktueller klinischer Untersuchungen sind. Dazu zählt die Behandlung der Divertikelerkrankung, der Clostridium-difficile-assoziierten Diarrhö und der pseudomembranösen Kolitis, der bakteriellen Fehlbesiedlung des Dünndarms, des Reizdarmsyndroms sowie der hepatischen Enzephalopathie. Diese Übersicht zeigt mögliche Einsatzgebiete in der Gastroenterologie auf und beurteilt kritisch den Stellenwert von Rifaximin in der Behandlung dieser Erkrankungen anhand neuester Daten.

Abstract

Rifaximin, a non-resorbable broadband antibiotic, was approved in Germany 2 years ago for the treatment of traveller’s diarrhoea caused by non-invasive enteropathogens. On account of the very good tolerance and the high efficacy against almost all enteropathogens this pharmaceutical, which has been available for 25 years, bears a high potential in many other indications which are currently under clinical investigations, including: symptomatic uncomplicated diverticular disease, Clostridium difficile-associated diarrhoea and pseudomembranous colitis, small bowel intestinal bacterial overgrowth, irritable bowel syndrome and hepathic encephalopathy. The present overview demonstrates potential indications in the field of gastroenterology and critically reviews the significance of rifiximin in the treatment of these diseases based on the latest clinica data.

Schlüsselwörter

bakterielle Fehlbesiedlung - Divertikulose - infektiöse Kolitis - Laktoseintoleranz - pseudomembranöse Kolitis - Colon irritabile

Key words

small bowel intestinal bacterial overgrowth - diverticular disease - infectious colitis - lactose intolerance - pseudomembranous colitis - irritable bowel syndrome

Literatur

• 1 Jiang Z D, Ke S, Palazzini E et al. In vitro activity and fecal concentration of rifaximin after oral administration.  Antimicrob Agents Chemother. 2000;  44 2205-2206
• 2 Descombe J J, Dubourg D, Picard M et al. Pharmacokinetic study of rifaximin after oral administration in healthy volunteers.  Int J Clin Pharmacol Res. 1994;  14 51-56
• 3 Gionchetti P, Rizzello F, Ferrieri A et al. Rifaximin in patients with moderate or severe ulcerative colitis refractory to steroid-treatment: a double-blind, placebo-controlled trial.  Dig Dis Sci. 1999;  44 1220-1221
• 4 Rizzello F, Gionchetti P, Venturi A et al. Rifaximin systemic absorption in patients with ulcerative colitis.  Eur J Clin Pharmacol. 1998;  54 91-93
• 5 Gomi H, Jiang Z D, Adachi J A et al. In vitro antimicrobial susceptibility testing of bacterial enteropathogens causing traveler’s diarrhea in four geographic regions.  Antimicrob Agents Chemother. 2001;  45 212-216
• 6 Ruiz J, Mensa L, O’Callaghan C et al. In vitro antimicrobial activity of rifaximin against enteropathogens causing traveler’s diarrhea.  Diagn Microbiol Infect Dis. 2007;  59 473-475
• 7 Steffen R, Sack D A, Riopel L et al. Therapy of travelers’ diarrhea with rifaximin on various continents.  Am J Gastroenterol. 2003;  98 1073-1078
• 8 Taylor D N, Bourgeois A L, Ericsson C D et al. A randomized, double-blind, multicenter study of rifaximin compared with placebo and with ciprofloxacin in the treatment of travelers’ diarrhea.  Am J Trop Med Hyg. 2006;  74 1060-1066
• 9 O’Connor J R, Galang M A, Sambol S P et al. Rifampin and rifaximin resistance in clinical isolates of Clostridium difficile.  Antimicrob Agents Chemother. 2008;  52 2813-2817
• 10 De-Leo C, Eftimiadi C, Schito G C. Rapid disappearance from the intestinal tract of bacteria resistant to rifaximin.  Drugs Exp Clin Res. 1986;  12 979-981
• 11 Brigidi P, Swennen E, Rizzello F et al. Effects of rifaximin administration on the intestinal microbiota in patients with ulcerative colitis.  J Chemother. 2002;  14 290-295
• 12 Dupont H L, Jiang Z D. Influence of rifaximin treatment on the susceptibility of intestinal Gram-negative flora and enterococci.  Clin Microbiol Infect. 2004;  10 1009-1011
• 13 Fumi A L, Trexler K. Rifaximin treatment for symptoms of irritable bowel syndrome.  Ann Pharmacother. 2008;  42 408-412
• 14 Bertoli D, Borelli G. Teratogenic action of Rifaximin in the rat and rabbit and its effect on perinatal development in the rat.  Boll Soc Ital Biol Sper. 1984;  60 1079-1085
• 15 Borelli G, Bertoli D. Acute, subacute, chronic toxicity and mutagenicity studies of rifaximin (L/ 105) in rats.  Chemioterapia. 1986;  5 263-267
• 16 Ma X, Shah Y M, Guo G L et al. Rifaximin is a gut-specific human pregnane X receptor activator.  J Pharmacol Exp Ther. 2007;  322 391-398
• 17 Trapnell C B, Connolly M, Pentikis H et al. Absence of effect of oral rifaximin on the pharmacokinetics of ethinyl estradiol/norgestimate in healthy females.  Ann Pharmacother. 2007;  41 222-228
• 18 Pentikis H S, Connolly M, Trapnell C B et al. The effect of multiple-dose, oral rifaximin on the pharmacokinetics of intravenous and oral midazolam in healthy volunteers.  Pharmacotherapy. 2007;  27 1361-1369
• 19 Dupont H L, Jiang Z D, Belkind-Gerson J et al. Treatment of travelers’ diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone.  Clin Gastroenterol Hepatol. 2007;  5 451-456
• 20 Dupont H L, Ericsson C D. Prevention and treatment of traveler’s diarrhea.  N Engl J Med. 1993;  328 1821-1827
• 21 Ericsson C D, Dupont H L. Rifaximin in the treatment of infectious diarrhea.  Chemotherapy. 2005;  51 /Suppl 1) 73-80
• 22 Gillis J C, Brogden R N. Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria.  Drugs. 1995;  49 467-484
• 23 Ruiz J, Mensa L, Pons M J et al. Development of Escherichia coli rifaximin-resistant mutants: frequency of selection and stability.  J Antimicrob Chemother. 2008;  61 1016-1019
• 24 Vitali B, Turroni S, Serina S et al. Molecular and phenotypic traits of in-vitro-selected mutants of Bifidobacterium resistant to rifaximin.  Int J Antimicrob Agents. 2008;  31 555-560
• 25 Dupont H L, Ericsson C D, Mathewson J J et al. Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers’ diarrhea.  Digestion. 1998;  59 708-714
• 26 Dupont H L, Jiang Z D, Ericsson C D et al. Rifaximin versus ciprofloxacin for the treatment of traveler’s diarrhea: a randomized, double-blind clinical trial.  Clin Infect Dis. 2001;  33 1807-1815
• 27 Dupont H L, Haake R, Taylor D N et al. Rifaximin treatment of pathogen-negative travelers’ diarrhea.  J Travel Med. 2007;  14 16-19
• 28 Dupont H L, Jiang Z D, Okhuysen P C et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers’ diarrhea.  Ann Intern Med. 2005;  142 805-812
• 29 Taylor D N, McKenzie R, Durbin A et al. Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge.  Clin Infect Dis. 2006;  42 1283-1288
• 30 Taylor D N, McKenzie R, Durbin A et al. Systemic pharmacokinetics of rifaximin in volunteers with shigellosis.  Antimicrob Agents Chemother. 2008;  52 1179-1181
• 31 Jiang Z D, Dupont H L, La R M et al. In vitro susceptibility of Clostridium difficile to rifaximin and rifampin in 359 consecutive isolates at a university hospital in Houston, Texas.  J Clin Pathol. 2010;  63 355-358
• 32 Dupont H L. Clinical practice. Bacterial diarrhea.  N Engl J Med. 2009;  361 1560-1569
• 33 Dupont H L. Systematic review: the epidemiology and clinical features of travellers’ diarrhoea.  Aliment Pharmacol Ther. 2009;  30 187-196
• 34 Amenta M, le Nogare E R, Colomba C et al. Intestinal protozoa in HIV-infected patients: effect of rifaximin in Cryptosporidium parvum and Blastocystis hominis infections.  J Chemother. 1999;  11 391-395
• 35 Schneider T, Eckmanns T, Ignatius R et al. Clostridium-difficile-assoziierte Diarrhö: Ein zunehmendes klinisches Problem durch neue hochvirulente Erreger.  Dtsch Arztebl. 2007;  104 1588-1594
• 36 Eichel-Streiber C, Braun V. Das difficile Clostridium.  J Lab Med. 2008;  32 219-234
• 37 Gerding D N, Muto C A, Owens R C et al. Treatment of Clostridium difficile infection.  Clin Infect Dis. 2008;  46 (Suppl 1) S32-S42
• 38 Kokkotou E, Moss A C, Michos A et al. Comparative efficacies of rifaximin and vancomycin for treatment of Clostridium difficile-associated diarrhea and prevention of disease recurrence in hamsters.  Antimicrob Agents Chemother. 2008;  52 1121-1126
• 39 Surawicz C M. Antibiotic-associated diarrhea and pseudomembranous colitis: are they less common with poorly absorbed antimicrobials?.  Chemotherapy. 2005;  51 (Suppl 1) 81-89
• 40 Garey K W, Salazar M, Shah D et al. Rifamycin antibiotics for treatment of Clostridium difficile-associated diarrhea.  Ann Pharmacother. 2008;  42 827-835
• 41 Boero M, Berti E, Morgando A et al. Treatment for colitis caused by Clostridium difficile: results of a randomized, open-label study of rifaximin vs. vancomycin.  Microbiologia Medica. 1990;  5 74-77
• 42 Johnson S, Schriever C, Galang M et al. Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin.  Clin Infect Dis. 2007;  44 846-848
• 43 Garey K W, Jiang Z D, Bellard A et al. Rifaximin in Treatment of Recurrent Clostridium difficile-associated Diarrhea: An Uncontrolled Pilot Study.  J Clin Gastroenterol. 2009;  43 91-93
• 44 Bascu P P, Diani A, Rayapudi K et al. Rifaximin salvage therapy for metranizole-resistant clostridium difficile infection – a prospective trial [Abstract].  Gastroenterology. 2009;  104 A1099
• 45 Curry S R, Marsh J W, Shutt K A et al. High frequency of rifampin resistance identified in an epidemic Clostridium difficile clone from a large teaching hospital.  Clin Infect Dis. 2009;  48 425-429
• 46 Wettstein M, Kircheis G, Häussinger D. Hepatische Enzephalopathie – Diagnostik.  Dtsch Med Wochenschr. 2003;  128 2654-2657
• 47 Als-Nielsen B, Gluud L L, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials.  BMJ. 2004;  328 1046
• 48 Bucci L, Palmieri G C. Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy.  Curr Med Res Opin. 1993;  13 109-118
• 49 De Marco F, Santamaria Amato P, D’Arienzo A. Rifaximin in collateral treatment of portal-systemic encephalopathy: A preliminary report.  Curr Ther Res. 1984;  36 668-674
• 50 DiPiazza S, Gabriella F M, Valenza L M et al. Rifaximine versus neomycin in the treatment of portosystemic encephalopathy.  Ital J Gastroenterol. 1991;  23 403-407
• 51 Fera G, Agostinacchio F, Nigro M et al. Rifaximin in the treatment of hepatic encophalopathy.  Eur J Res. 1993;  4 109-118
• 52 Festi D, Mazzella G, Parini P et al. Treatment of hepatic encephalopathy with non-absorbable antibiotics.  Ital J Gastroenterol. 1992;  24 14-16
• 53 Loguercio C, Federico A, De G et al. Cyclic treatment of chronic hepatic encephalopathy with rifaximin. Results of a double-blind clinical study.  Minerva Gastroenterol Dietol. 2003;  49 53-62
• 54 Mas A, Rodes J, Sunyer L et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial.  J Hepatol. 2003;  38 51-58
• 55 Massa M D, Vallerino M D, Dodero M D. Treatment of hepatic encephalopathy with rifaximin: Double-blind, double-dummy study versus lactulose.  Eur J Clin Res. 1993;  4 7-18
• 56 Miglio F, Valpiani D, Rossellini S R et al. Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial.  Curr Med Res Opin. 1997;  13 593-601
• 57 Parini P, Cipolla A, Ronchi M et al. Effect of rifaximin in the treatment of portal-systemic encephalopathy.  Curr Ther Res. 1992;  52 34-39
• 58 Pedretti G, Calzetti C, Missale G et al. Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial.  Ital J Gastroenterol. 1991;  23 175-178
• 59 Testa R, Eftimiadi C, Sukkar G S et al. A non-absorbable rifamycin for treatment of hepatic encephalopathy.  Drugs Exp Clin Res. 1985;  11 387-392
• 60 Williams R, James O F, Warnes T W et al. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study.  Eur J Gastroenterol Hepatol. 2000;  12 203-208
• 61 Zeneroli M L, Avallone R, Corsi L et al. Management of hepatic encephalopathy: role of rifaximin.  Chemotherapy. 2005;  51 (Suppl 1) 90-95
• 62 Paik Y H, Lee K S, Han K H et al. Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study.  Yonsei Med J. 2005;  46 399-407
• 63 Bass N M, Mullen K D, Sanyal A et al. Rifaximin treatment in hepatic encephalopathy.  N Engl J Med. 2010;  362 1071-1081
• 64 Neff G W, Kemmer N, Zacharias V C et al. Analysis of hospitalizations comparing rifaximin versus lactulose in the management of hepatic encephalopathy.  Transplant Proc. 2006;  38 3552-3555
• 65 Vlachogiannakos J, Saveriadis A S, Viazis N et al. Intestinal decontamination improves liver haemodynamics in patients with alcohol-related decompensated cirrhosis.  Aliment Pharmacol Ther. 2009;  29 992-999
• 66 Attar A, Flourie B, Rambaud J C et al. Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: a crossover, randomized trial.  Gastroenterology. 1999;  117 794-797
• 67 Peralta S, Cottone C, Doveri T et al. Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms: experience with Rifaximin.  World J Gastroenterol. 2009;  15 2628-2631
• 68 Husebye E. The pathogenesis of gastrointestinal bacterial overgrowth.  Chemotherapy. 2005;  51 (Suppl 1) 1-22
• 69 Gasbarrini A, Lauritano E C, Gabrielli M et al. Small intestinal bacterial overgrowth: diagnosis and treatment.  Dig Dis. 2007;  25 237-240
• 70 Lauritano E C, Gabrielli M, Lupascu A et al. Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth.  Aliment Pharmacol Ther. 2005;  22 31-35
• 71 Esposito I, De L A, Di G G et al. Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease: an observation on non-absorbable antibiotics.  World J Gastroenterol. 2007;  13 6016-6021
• 72 Cuoco L, Salvagnini M. Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin.  Minerva Gastroenterol Dietol. 2006;  52 89-95
• 73 Majewski M, Sostarich S, Foran P et al. Is rifaximin effective treatment for small intestinal bacterial overgrowth? [ACG abstract 293].  Am J Gastroenterol. 2006;  101 (Suppl) S141
• 74 Scarpellini E, Gabrielli M, Lauritano C E et al. High dosage rifaximin for the treatment of small intestinal bacterial overgrowth.  Aliment Pharmacol Ther. 2007;  25 781-786
• 75 Lauritano E C, Gabrielli M, Scarpellini E et al. Antibiotic therapy in small intestinal bacterial overgrowth: rifaximin versus metronidazole.  Eur Rev Med Pharmacol Sci. 2009;  13 111-116
• 76 Di Stefano M, Malservisi S, Veneto G et al. Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth.  Aliment Pharmacol Ther. 2000;  14 551-556
• 77 Pimentel M, Park S, Mirocha J et al. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial.  Ann Intern Med. 2006;  145 557-563
• 78 Pimentel M. Review of rifaximin as treatment for SIBO and IBS.  Expert Opin Investig Drugs. 2009;  18 349-358
• 79 Colecchia A, Sandri L, Capodicasa S et al. Diverticular disease of the colon: new perspectives in symptom development and treatment.  World J Gastroenterol. 2003;  9 1385-1389
• 80 Papi C, Koch M, Capurso L. Management of diverticular disease: is there room for rifaximin?.  Chemotherapy. 2005;  51 (Suppl 1) 110-114
• 81 Papi C, Ciaco A, Koch M et al. Efficacy of rifaximin on symptoms of uncomplicated diverticular disease of the colon. A pilot multicentre open trial. Diverticular Disease Study Group.  Ital J Gastroenterol. 1992;  24 452-456
• 82 Latella G, Pimpo M T, Sottili S et al. Rifaximin improves symptoms of acquired uncomplicated diverticular disease of the colon.  Int J Colorectal Dis. 2003;  18 55-62
• 83 Papi C, Ciaco A, Koch M et al. Efficacy of rifaximin in the treatment of symptomatic diverticular disease of the colon. A multicentre double-blind placebo-controlled trial.  Aliment Pharmacol Ther. 1995;  9 33-39
• 84 Colecchia A, Vestito A, Pasqui F et al. Efficacy of long term cyclic administration of the poorly absorbed antibiotic Rifaximin in symptomatic, uncomplicated colonic diverticular disease.  World J Gastroenterol. 2007;  13 264-269
• 85 Di Mario F, Aragona G, Leandro G et al. Efficacy of mesalazine in the treatment of symptomatic diverticular disease.  Dig Dis Sci. 2005;  50 581-586
• 86 Comparato G, Fanigliulo L, Aragona G et al. Quality of life in uncomplicated symptomatic diverticular disease: is it another good reason for treatment?.  Dig Dis. 2007;  25 252-259
• 87 Comparato G, Fanigliulo L, Cavallaro L G et al. Prevention of complications and symptomatic recurrences in diverticular disease with mesalazine: a 12-month follow-up.  Dig Dis Sci. 2007;  52 2934-2941
• 88 Tursi A, Brandimarte G, Daffina R. Long-term treatment with mesalazine and rifaximin versus rifaximin alone for patients with recurrent attacks of acute diverticulitis of colon.  Dig Liver Dis. 2002;  34 510-515
• 89 D’Inca R, Pomerri F, Vettorato M G et al. Interaction between rifaximin and dietary fibre in patients with diverticular disease.  Aliment Pharmacol Ther. 2007;  25 771-779
• 90 Tursi A, Brandimarte G, Giorgetti G M et al. Assessment of small intestinal bacterial overgrowth in uncomplicated acute diverticulitis of the colon.  World J Gastroenterol. 2005;  11 2773-2776
• 91 Gionchetti P, Rizzello F, Morselli C et al. Management of inflammatory bowel disease: does rifaximin offer any promise?.  Chemotherapy. 2005;  51 (Suppl 1) 96-102
• 92 Lukas M, Konecny M, Zboril V. Rifaximin in patients with mild to moderate activity of ulcerative colitis: An open label study.  Gastroenterology. 2002;  122 (Suppl 1) A434
• 93 Guslandi M, Giollo M, Testoni P A. Corticosteroid-sparing effect of rifaximin, a nonabsorbable oral antibiotic, in active ulcerative colitis: Preliminary clinical experience.  Curr Ther Res. 2004;  65 292-296
• 94 Gionchetti P, Rizzello F, Venturi A et al. Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis.  Aliment Pharmacol Ther. 1999;  13 713-718
• 95 Isaacs K L, Sandler R S, Abreu M et al. Rifaximin for the treatment of active pouchitis: a randomized, double-blind, placebo-controlled pilot study.  Inflamm Bowel Dis. 2007;  13 1250-1255
• 96 Shen B, Remzi F H, Lopez A R et al. Rifaximin for maintenance therapy in antibiotic-dependent pouchitis.  BMC Gastroenterol. 2008;  8 26
• 97 Campieri M, Rizzello F, Venturi A et al. Combination of antibiotic and probiotic treatment is efficacious in prophylaxis of post-operative recurrence of Crohn’s disease: a randomised controlled study vs mesalazine [Abstract].  Gastroenterology. 2000;  118 A781
• 98 Shafran I, Burgunder P. Rifaximin for the treatment of newly diagnosed Crohn’s disease: a case series.  Am J Gastroenterol. 2008;  103 2158-2160