Z Gastroenterol 2011; 49(8): 989-996
DOI: 10.1055/s-0031-1273390
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Aktueller Stellenwert von Fluorchinolonen in der Helicobacter-pylori-Therapie

Current Value of Quinolones in Helicobacter pylori TherapyS. Krasz1 , S. Miehlke2 , M. Berning1 , A. Morgner3 , J. Labenz4
  • 1Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden
  • 2Magen-Darm-Zentrum, Internistische Kooperation Eppendorf, Hamburg
  • 3Organisations- und Unternehmensentwicklung, Universitätsklinikum Dresden
  • 4Innere Medizin, Diakonie Klinikum Jung-Stilling, Siegen
Further Information

Publication History

Manuskript eingetroffen: 7.1.2011

Manuskript akzeptiert: 26.4.2011

Publication Date:
02 August 2011 (online)

Zusammenfassung

Zunehmende Resistenzen gegen die regelmäßig verwendeten Antibiotika Clarithromycin und Metronidazol haben zu sinkenden Eradikationsraten in der Standard-Erstlinientherapie der Helicobacter-pylori-Infektion geführt. Dies erfordert die Evaluation neuer Substanzen und Therapieschemata, um alternative Therapiestrategien anbieten zu können. Fluorchinonolone haben ein breites Wirkspektrum gegen Gram-positive und Gram-negative Erreger und sind dabei gut verträglich. In der Zweitlinientherapie der Eradikation von Helicobacter pylori sind Fluorchinolone aufgrund von vielen Studienergebnissen mittlerweile anerkannt und werden in aktuellen Leitlinien empfohlen. In den letzten Jahren wurden auch Fluorchinolon-haltige Schemata mit Levofloxacin und Moxifloxacin in der Erstlinientherapie der H.-pylori-Infektion intensiv untersucht. Allerdings müssen vor dem Hintergrund bereits steigender Resistenzraten von Helicobacter pylori gegen Fluorchinolone Vor- und Nachteile dieser Substanzen kritisch abgewogen werden. Erste präklinische und klinische Erfahrungen liegen bereits zu dem neuen Fluorchinolon Sitafloxacin vor, das möglicherweise eine Resistenz gegen herkömmliche Fluorchinolone überwinden kann. Diese Arbeit gibt einen aktuellen Überblick über den gesicherten Stellenwert der Fluorchinolone sowie über mögliche zukünftige Indikationen in der H.-pylori-Therapie.

Abstract

Eradication rates in first-line Helicobacter pylori therapy have been declining over the last decades, mainly due to increasing resistance against the recommended antibiotics clarithromycin and metronidazole. Thus, there is a need to evaluate novel regimens and substances to offer effective alternative treatment strategies. New generation quinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against various Gram-positive and Gram-negative strains and are mostly well tolerated. Based on a large number of studies, quinolones have been introduced in second-line and rescue treatment and are recommended for these indications in current guidelines. Various studies have investigated alternative strategies for first-line treatment including quinolone-based regimens. In the context of increasing resistance rates of Helicobacter pylori against quinolones some risks and benefits have to be considered when using quinolones as a first-line strategy. Besides numerous studies investigating levofloxacin and moxifloxacin there are some promising results for the new substance sitafloxacin, which might overcome primary resistance of Helicobacter pylori against conventional quinolones.

Literatur

  • 1 Fischbach W, Malfertheiner P, Hoffmann J C et al. S3-guideline „Helicobacter pylori and gastroduodenal ulcer disease”.  Z Gastroenterol. 2009;  47 68-102
  • 2 Malfertheiner P, Megraud F, O’Morain C et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report.  Gut,. 2007;  56 772-781
  • 3 Chey W D, Wong B C. American College of Gastroenterology guideline on the management of Helicobacter pylori infection.  Am J Gastroenterol. 2007;  102 1808-25
  • 4 Perri F, Villani M R, Festa V et al. Predictors of failure of Helicobacter pylori eradication with the standard ‘Maastricht triple therapy’.  Aliment Pharmacol Ther. 2001;  15 1023-1029
  • 5 Fennerty M B, Lieberman D A, Vakil N et al. Effectiveness of Helicobacter pylori therapies in a clinical practice setting.  Arch Intern Med. 1999;  159 1562-1566
  • 6 Zullo A, Hassan C, Andriani A et al. Eradication therapy for Helicobacter pylori in patients with gastric MALT lymphoma: a pooled data analysis.  Am J Gastroenterol. 2009;  104 1932-1937 ; quiz 1938
  • 7 Megraud F. H pylori antibiotic resistance: prevalence, importance, and advances in testing.  Gut. 2004;  53 1374-1384
  • 8 Heep M, Kist M, Strobel S et al. Secondary resistance among 554 isolates of Helicobacter pylori after failure of therapy.  Eur J Clin Microbiol Infect Dis. 2000;  19 538-541
  • 9 De Sarro A, De Sarro G. Adverse reactions to fluoroquinolones. An overview on mechanistic aspects.  Curr Med Chem,. 2001;  8 371-84
  • 10 Moore R A, Beckthold B, Wong S et al. Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin-resistant mutants of Helicobacter pylori.  Antimicrob Agents Chemother. 1995;  39 107-111
  • 11 Debets-Ossenkopp Y J, Herscheid A J, Pot R G et al. Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxycillin, tetracycline and trovafloxacin in The Netherlands.  J Antimicrob Chemother. 1999;  43 511-515
  • 12 Tankovic J, Lascols C, Sculo Q et al. Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pylori.  Antimicrob Agents Chemother. 2003;  47 3942-3944
  • 13 Glocker E, Stueger H P, Kist M. Quinolone resistance in Helicobacter pylori isolates in Germany.  Antimicrob Agents Chemother. 2007;  51 346-349
  • 14 Boyanova L, Gergova G, Nikolov R et al. Prevalence and evolution of Helicobacter pylori resistance to 6 antibacterial agents over 12 years and correlation between susceptibility testing methods.  Diagn Microbiol Infect Dis. 2008;  60 409-415
  • 15 Hung K H, Sheu B S, Chang W L et al. Prevalence of primary fluoroquinolone resistance among clinical isolates of Helicobacter pylori at a University Hospital in Southern Taiwan.  Helicobacter. 2009;  14 61-65
  • 16 Chisholm S A, Owen R J. Frequency and molecular characteristics of ciprofloxacin- and rifampicin-resistant Helicobacter pylori from gastric infections in the UK.  J Med Microbiol. 2009;  58 1322-1328
  • 17 Miyachi H, Miki I, Aoyama N et al. Primary levofloxacin resistance and gyrA/B mutations among Helicobacter pylori in Japan.  Helicobacter. 2006;  11 243-249
  • 18 Gisbert J P, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure.  Aliment Pharmacol Ther. 2006;  23 35-44
  • 19 Saad R J, Schoenfeld P, Kim H M et al. Levofloxacin-based triple therapy vs. bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis.  Am J Gastroenterol. 2006;  101 488-496
  • 20 Cheon J H, Kim N, Lee D H et al. Trial of moxifloxacin-containing triple therapy after initial and second-line treatment failures for Helicobacter pylori infection.  Korean J Gastroenterol. 2005;  45 111-117
  • 21 Cheon J H, Kim N, Lee D H et al. Efficacy of Moxifloxacin-Based Triple Therapy as Second-Line Treatment for Helicobacter pylori Infection.  Helicobacter. 2006;  11 46-51
  • 22 Kang J M, Kim N, Lee D H et al. Second-line treatment for Helicobacter pylori infection: 10-day moxifloxacin-based triple therapy vs. 2-week quadruple therapy.  Helicobacter. 2007;  12 623-628
  • 23 Yoon H, Kim N, Lee B H et al. Moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate.  Helicobacter. 2009;  14 77-85
  • 24 Zheng X L, Xu L. Efficacy of second-line treatment based on moxifloxacin triple therapy for Helicobacter pylori infection.  Zhonghua Yi Xue Za Zhi. 2010;  90 83-86
  • 25 Miehlke S, Schneider-Brachert W, Kirsch C et al. One-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for eradication of persistent Helicobacter pylori resistant to both metronidazole and clarithromycin.  Helicobacter. 2008;  13 69-74
  • 26 Bago J, Pevec B, Tomic M et al. Second-line treatment for Helicobacter pylori infection based on moxifloxacin triple therapy: a randomized controlled trial.  Wien Klin Wochenschr. 2009;  121 47-52
  • 27 Miehlke S, Krasz S, Schneider-Brachert W et al. Randomized Multicenter Study of Esomeprazole, Moxifloxacin and Amoxicillin for Second-Line or Rescue Treatment of Helicobacter pylori Infection.  Helicobacter. 2011;  in press
  • 28 Li Y, Huang X, Yao L et al. Advantages of Moxifloxacin and Levofloxacin-based triple therapy for second-line treatments of persistent Helicobacter pylori infection: a meta analysis.  Wien Klin Wochenschr. 2010;  122 413-422
  • 29 Cammarota G, Cianci R, Cannizzaro O et al. Efficacy of two one-week rabeprazole/levofloxacin-based triple therapies for Helicobacter pylori infection.  Aliment Pharmacol Ther. 2000;  14 1339-1343
  • 30 Di Caro S, Zocco M A, Cremonini F et al. Levofloxacin based regimens for the eradication of Helicobacter pylori.  Eur J Gastroenterol Hepatol. 2002;  14 1309-1312
  • 31 Nista E C, Candelli M, Zocco M A et al. Levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori eradication.  Am J Gastroenterol. 2006;  101 1985-1990
  • 32 Iacopini F, Crispino P, Paoluzi O A et al. One-week once-daily triple therapy with esomeprazole, levofloxacin and azithromycin compared to a standard therapy for Helicobacter pylori eradication.  Dig Liver Dis. 2005;  37 571-576
  • 33 Rispo A, Di Girolamo E, Cozzolino A et al. Levofloxacin in first-line treatment of Helicobacter pylori infection.  Helicobacter. 2007;  12 364-365
  • 34 Marzio L, Coraggio D, Capodicasa S et al. Role of the preliminary susceptibility testing for initial and after failed therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and esomeprazole.  Helicobacter. 2006;  11 237-242
  • 35 Antos D, Schneider-Brachert W, Bastlein E et al. 7-day triple therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and high-dose esomeprazole in patients with known antimicrobial sensitivity.  Helicobacter. 2006;  11 39-45
  • 36 Gisbert J P, Fernandez-Bermejo M, Molina-Infante J et al. First-line triple therapy with levofloxacin for Helicobacter pylori eradication.  Aliment Pharmacol Ther. 2007;  26 495-500
  • 37 Gisbert J P, Bermejo M F, Infante J M et al. Levofloxacin, Amoxicillin, and Omeprazole as first-line triple therapy for Helicobacter pylori eradication.  J Clin Gastroenterol. 2009;  43 384-385
  • 38 Molina-Infante J, Perez-Gallardo B, Fernandez-Bermejo M et al. Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication.  Aliment Pharmacol Ther. 2010;  31 1077-1084
  • 39 Castro-Fernandez M, Lamas E, Perez-Pastor A et al. Efficacy of triple therapy with a proton pump inhibitor, levofloxacin, and amoxicillin as first-line treatment to eradicate Helicobacter pylori.  Rev Esp Enferm Dig. 2009;  101 395-398, 399 – 402
  • 40 Schrauwen R W, Janssen M J, Boer W A. Seven-day PPI-triple therapy with levofloxacin is very effective for Helicobacter pylori eradication.  Neth J Med. 2009;  67 96-101
  • 41 Liou J M, Lin J T, Chang C Y et al. Levofloxacin-based and clarithromycin-based triple therapies as first-line and second-line treatments for Helicobacter pylori infection: a randomised comparative trial with crossover design.  Gut. 2010;  59 572-578
  • 42 Di Caro de S, Ojetti V, Zocco M A et al. Mono, dual and triple moxifloxacin-based therapies for Helicobacter pylori eradication.  Aliment Pharmacol Ther. 2002;  16 527-532
  • 43 Nista E C, Candelli M, Zocco M A et al. Moxifloxacin-based strategies for first-line treatment of Helicobacter pylori infection.  Aliment Pharmacol Ther. 2005;  21 1241-1247
  • 44 Sacco F, Spezzaferro M, Amitrano M et al. Efficacy of four different moxifloxacin-based triple therapies for first-line H. pylori treatment.  Dig Liver Dis. 2010;  42 110-114
  • 45 Bago P, Vcev A, Tomic M et al. High eradication rate of H. pylori with moxifloxacin-based treatment: a randomized controlled trial.  Wien Klin Wochenschr. 2007;  119 372-378
  • 46 Bago J, Majstorovic K, Belosic-Halle Z et al. Antimicrobial resistance of H. pylori to the outcome of 10-days vs. 7-days Moxifloxacin based therapy for the eradication: a randomized controlled trial.  Ann Clin Microbiol Antimicrob. 2010;  9 13
  • 47 Sezgin O, Altintas E, Ucbilek E et al. Low efficacy rate of moxifloxacin-containing Helicobacter pylori eradication treatment: in an observational study in a Turkish population.  Helicobacter. 2007;  12 518-522
  • 48 Kilic Z M, Koksal A S, Cakal B et al. Moxifloxacine plus amoxicillin and ranitidine bismuth citrate or esomeprazole triple therapies for Helicobacter pylori infection.  Dig Dis Sci. 2008;  53 3133-3137
  • 49 Sanchez J E, Saenz N G, Rincon M R et al. Susceptibility of Helicobacter pylori to mupirocin, oxazolidinones, quinupristin/dalfopristin and new quinolones.  J Antimicrob Chemother. 2000;  46 283-285
  • 50 Murakami K, Okimoto T, Kodama M et al. Sitafloxacin activity against Helicobacter pylori isolates, including those with gyrA mutations.  Antimicrob Agents Chemother. 2009;  53 3097-3099
  • 51 Suzuki H, Nishizawa T, Muraoka H et al. Sitafloxacin and garenoxacin may overcome the antibiotic resistance of Helicobacter pylori with gyrA mutation.  Antimicrob Agents Chemother. 2009;  53 1720-1721
  • 52 Suzuki H, Nishizawa T, Saito Y et al. Sitafloxacin-based third-line eradication of H. pylori.  Gastroenterol. 2010;  (DDW abstract)
  • 53 Furuta T SM, Kodaira C, Nishino M et al. Comparison of triple rabeprazole/metronidazole/sitafloxacin therapy with triple rabeprazole/amoxicillin/sitafloxacin therapy as the third rescue regimen for eradication of H. pylori.  Gastroenterol. 2010;  (DDW abstract)
  • 54 Berning M, Krasz S, Miehlke S. Should quinolones come first in Helicobacter pylori therapy?.  Ther Adv Gastroenterol. 2011;  4 103-114
  • 55 Zullo A, Perna F, Hassan C et al. Primary antibiotic resistance in Helicobacter pylori strains isolated in northern and central Italy.  Aliment Pharmacol Ther. 2007;  25 1429-1434
  • 56 Cabrita J, Oleastro M, Matos R et al. Features and trends in Helicobacter pylori antibiotic resistance in Lisbon area, Portugal (1990 – 1999).  J Antimicrob Chemother. 2000;  46 1029-1031
  • 57 Nishizawa T, Suzuki H, Kurabayashi K et al. Gatifloxacin resistance and mutations in gyra after unsuccessful Helicobacter pylori eradication in Japan.  Antimicrob Agents Chemother. 2006;  50 1538-1540
  • 58 Branca G, Spanu T, Cammarota G et al. High levels of dual resistance to clarithromycin and metronidazole and in vitro activity of levofloxacin against Helicobacter pylori isolates from patients after failure of therapy.  Int J Antimicrob Agents. 2004;  24 433-438
  • 59 Perna F, Zullo A, Ricci C et al. Levofloxacin-based triple therapy for Helicobacter pylori re-treatment: role of bacterial resistance.  Dig Liver Dis. 2007;  39 1001-1005
  • 60 Graham D Y, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance.  Gut. 2010;  59 1143-1153
  • 61 Wang L H, Cheng H, Hu F L et al. Distribution of gyrA mutations in fluoroquinolone-resistant Helicobacter pylori strains.  World J Gastroenterol. 2010;  16 2272-7227
  • 62 Bogaerts P, Berhin C, Nizet H et al. Prevalence and mechanisms of resistance to fluoroquinolones in Helicobacter pylori strains from patients living in Belgium.  Helicobacter. 2006;  11 441-445
  • 63 Cattoir V, Nectoux J, Lascols C et al. Update on fluoroquinolone resistance in Helicobacter pylori: new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility.  Int J Antimicrob Agents. 2007;  29 389-396
  • 64 Di Caro S, Franceschi F, Mariani A et al. Second-line levofloxacin-based triple schemes for Helicobacter pylori eradication.  Dig Liver Dis. 2009;  41 480-485

Prof. Dr. Stephan Miehlke

Magen-Darm-Zentrum, Internistische Kooperation Eppendorf

Eppendorfer Landstr. 42

20249 Hamburg

Phone:  ++ 49/4 04 60 20 01

Fax:  ++ 49/40 47 35 47

Email: prof.miehlke@mdz-hamburg.de

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