Zusammenfassung
EINLEITUNG: In der klinischen Praxis stellt die Eradikation von Helikobacter pylori (HP) noch immer eine problematische Therapie dar. Ziel ist, eine hohe Eradikationsrate zu einem niedrigen Preis zu erzielen; die derzeitigen Behandlungsmöglichkeiten geben uns dazu die Möglichkeit. Kürzlich veröffentlichte Resultate mit einer auf Moxifloxacin basierten Therapie zeigten eine niedrige Resistenzrate und eine gute Kompliance. Die vorliegende Studie untersucht die Wirksamkeit des Einsatzes von Moxifloxacin im Rahmen einer Triple-Therapie zur Eradikation von HP. ZIEL UND METHODEN: Ziel unserer Studie war es, die Wirksamkeit einer einwöchigen Moxifloxacin-basierten HP-Eradikationstherapie mit der Standard-Therapie zur vergleichen. 277 HP-positive Patienten mit einer Dyspepsie ohne Ulcus wurden in 4 Gruppen randomisiert: MML Gruppe: Moxifloxacin 400 mg/Tag, Metronidazol 2 × 400 mg/Tag, Lansoprazol 30 mg 2 × tgl; MAL Gruppe: Moxifloxacin 400 mg/Tag, Amoxicillin 1 g 2 × tgl, Lansoprazol 30 mg 2 × tgl; CML Gruppe: Clarithromycin 500 mg 2 × tgl., Metronidazol 400 mg 2 × tgl, Lansoprazol 30 mg 2 × tgl; und die CAL Gruppe: Clarithromycin 500 mg 2 × tgl, Amoxicillin 1 g 2 × tgl, Lansoprazol 30 mg 2 × tgl. Zur Erfassung der Prävalenz des HP wurden die Patienten mittels dem CLO Test untersucht. Außerdem wurde vor der Randomisierung und 4–6 Wochen nach Ende der Therapie gastroskopisch eine Histologie gewonnen und eine Kultur angelegt. Die bakterielle Empfindlichkeit auf Clarithromycin und Moxifloxacin wurden durch den E-Test bestimmt. ERGEBNISSE: 265 Patienten (95,6%) vollendeten die Studie. Die HP-Eradikationsrate war entsprechend der ITT und der PP Analysen in der MML Gruppe 93,5% (58/62) und 96,7% (58/60); in der MAL Gruppe 86,4% (57/66) und 90,5% (57/63), in der CML Gruppe 70,4% (50/71) und 75,8% (50/66) sowie in der CAL Gruppe 78,2% (61/78) sowie 80,2% (61/76). Die Behandlungsprotokolle mit Moxifloxacin waren waren sowohl in der ITT als auch in der PP Analyse signifikant erfolgreicher als die Clarithromycin-basierten Therapieregimes. Von den 238 Patienten (86% der gesamten Studiengruppe) waren 10,8% primär gegen Clarithromycin und 5,9% primär gegen Moxifloxacin resistent. Die Eradikation der Moxifloxacin-sensitiven/resistenten Keimstämme lag bei 98,1/75% für das MML (p < 0,01) und bei 99,1/66,7% für das MAL Regime (p = n.s.), verglichen mit dem Erfolg bei Moxifloxacin-sensitiven Stämmen von 98,1/91,1% (p < 0,05) bzw. Moxifloxacin-resistenten von 75/66,7% (p = n.s.) für die MML und MAL Gruppen. Die Behandlungsprotokolle mit Clarithromycin unterschieden sich bezüglich ihrer Wirksamkeit, sensitive oder resistente Keimstämme zu eradizieren, nicht signifikant. SCHLUSSFOLGERUNG: Triple-Therapien mit Moxifloxacin zeigten höhere Eradikationsraten mit weniger Nebenwirkungen als die bisherige Standardtherapie, sowie eine gute Kompliance. Außerdem macht die zunehmende Prävalenz der Resistenz gegenüber Clarithromycin Moxifloxacin-basierte Therapieprotokolle wahrscheinlich zu einer wirksamen und sicheren Option zur Behandlung einer Infektion mit HP.
Summary
INTRODUCTION: Eradication of Helicobacter pylori remains a problematic treatment issue in clinical practice. The intention is to find a treatment that achieves a high rate of eradication at a low price and treatment options that are now used give us the opportunity to achieve this goal. Recently published results showing a low rate of resistance and better compliance with moxifloxacin-based treatment regimens indicate the need to investigate its efficacy in H. pylori eradication. This study is based on proving the efficacy of moxifloxacin in H. pylori eradication within the triple therapy. AIMS AND METHODS: The aim of the study was to compare the efficacy of one week of moxifloxacin-based treatment with the standard treatment for H. pylori eradication. Patients with H. pylori infection and non-ulcer dyspepsia (n = 277) were randomly divided into four groups to receive: moxifloxacin 400 mg/d, metronidazole 400 mg twice daily, lansoprazole 30 mg twice daily (MML group); moxifloxacin 400 mg/d, amoxicillin 1 g twice daily, lansoprazole 30 mg twice daily (MAL group); clarithromycin 500 mg twice daily, metronidazole 400 mg twice daily, lansoprazole 30 mg twice daily (CML group); clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, lansoprazole 30 mg twice daily (CAL group). The patients were assessed for prevalence of H. pylori using the CLO test, histology and culture on gastric biopsy samples obtained during upper gastrointestinal endoscopy before randomization and 4–6 weeks after completion of treatment. Bacterial sensitivity to clarithromycin and moxifloxacin was determined with the E-test. RESULTS: 265 (95.6%) patients completed the study forming the basis for PP analysis. Eradication rates of H. pylori in ITT and in PP analyses were: in the MML group 93.5% (58/62) and 96.7% (58/60), respectively; in the MAL group 86.4% (57/66) and 90.5% (57/63); in the CML group 70.4% (50/71) and 75.8% (50/66); and in the CAL group 78.2% (61/78) and 80.2% (61/76). Moxifloxacin treatment protocols were significantly more effective on both ITT and PP analyses than the clarithromycin based protocols with only one exception (MAL vs. CAL on ITT analysis). Among 238 patients (86% of the entire study group), strains showing primary resistance to clarithromycin were found in 10.8% and to moxifloxacin in 5.9%. Eradication of moxifloxacin sensitive/resistant strains was 98.1%/75% for MML (p < 0.01) and 91.1%/66.7% for MAL (p = n.s.); comparison of eradication of sensitive strains in MML and MAL regimens was 98.1%/91.1% (p < 0.05), and for resistant strains 75%/66.7% (p = n.s.). CML and CAL protocols did not differ in efficacy of eradication of clarithromycin sensitive or resistant strains. CONCLUSION: Moxifloxacin-based triple therapies showed higher eradication rates with few side effects and good drug compliance when compared with standard H. pylori treatments. Moreover, the increased prevalence of clarithromycin resistance suggests that moxifloxacin-based regimens could be safe and effective options in treatment of H. pylori infection.
References
Axon AT, O'Morain CA, Bardhan KD, Crowe JP, Beattie AD, Thompson RP, et al (1997) Randomized controlled study of recurrence of gastric ulcer after treatment for eradication of Helicobacter pylori infection. BMJ 314: 565–568
Van der Hulst RW, Rauws EA, Koycu B, Keller JJ, Bruno MJ, Tijssen JG, et al (1997) Prevention of ulcer recurrence after eradication of Helicobacter pylori: a prospective long-term follow up study. Gastroenterology 113: 1082–1086
Malfertheiner P, Megraud F, O'Morain C, et al (2002) Current concepts in the management of Helicobacter pylori infection – The Maastricht 2–2000 Consensus Report. Aliment Pharmacol Ther 16: 167–180
Graham DY (1998) Therapy of Helicobacter pylori: current status and issues. Gastroenterology 118 [Suppl 1]: S2–S8
Graham DY (1998) Antibiotic resistance in Helicobacter pylori: implications for therapy. Gastroenterology 115: 1272–1277
Megraud F, Doermann HP (1998) Clinical relevance of resistant strains of Helicobacter pylori: a review of current data. Gut 43 [Suppl 1]: S61–S65
Ducons JA, Santolaria S, Guirao R, Ferrero M, Montoro M, Gomollon F (1999) Impact of clarithromycin resistance on the effectiveness of a regimen for Helicobacter pylori: a prospective study of one week lansoprazole, amoxicillin and clarithromycin in active peptic ulcer. Aliment pharmacol Ther 13: 775–780
Graham DY, Lew GM, Malaty HM, Evans DG, Evans DJ, Saeed ZA, et al (1992) Factors influencing the eradication of H. pylori with triple therapy. Gastroenterology 102: 493–496
Cammarota G, Cianci R, Cannizzaro O, et al (2000) Efficacy of two one-week rabeprazole/levofloxacin-based triple therapies for Helicopacter pylori infection. Aliment Pharmacol Ther 14: 1339–1343
Di Caro S, Zocco AM, Cremonini F, et al (2002) Levofloxacin based regimens for eradication of Helicobacter pylori. Eur J Gastroenterol Hepatol 14: 1309–1312
Di Caro S, Ojjeti V, Zocco MA, et al (2002) Mono, dual and triple moxifloxacin-based therapies for Helicobacter pylori eradication. Aliment Pharmacol Ther 16: 527–532
Nista EC, Candelli M, Zocco MA, Cazzato IA, Cremonini F, et al (2005) Moxifloxacin-based strategies for first-line treatment of Helicobacter pylori infection. Aliment Pharmacol Ther 21: 1241–1247
Ball P (2000) Moxifloxacin: an 8-methoxyquinolone antibacterial with enhanced potency. Int J Clin Pract 54: 329–332
Edlum C, Beyer G, Hiemer-Bau M, et al (2000) Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora. Scand J Infect Dis 32: 81–85
Moore RA, Beckthold B, Wong S, et al (1995) Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin-resistant mutants of Helicobacter pylori. Antimicrob Agents Chemother 39: 107–111
Kusters JG, Kuipers EJ (2001) Antibiotic resistance of Helicobacter pylori. J Appl Microbiol 90: 134S
Debets-Ossenkopp YJ, Herscheid A, Pot RGJ, et al (1999) Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxicillin, tetracycline and trovafloxacin in The Netherlands. J Antimicrob Chemother 43: 511–560
Teare L, Peters T, Saverymuttu S, et al (1999) Antibiotic resistance in Helicobacter pylori. Lancet 353: 242
Pilloto A, Rassu M, Leandro G, et al (2000) Prevalence of Helicobacter pylori resistance to antibiotics in Northeast Italy: a multicentre study. GISU: Interdisciplinary Group for the Study of Ulcer. Dig Liver Dis 32: 763–768
Cabrita J, Oleastro M, Matos R, et al (2000) Features and trends in Helicobacter pylori antibiotic resistance in Lisbon area, Portugal (1990–1999). J Antimicrob Chemother 46: 1029–1031
Bago J, Halle ZB, Strinic D, et al (2002) The impact of primary resistance on the efficacy of ranitidine bismuth citrate vs. omeprazole-based 1-week triple therapies in H. pylori eradication-a randomized controlled trial. Wien Klin Wochenschr 114: 448–453
Bago J, Galovic A, Halle ZB, et al (2004) Comparison of the efficacy of 250 mg and 500 mg clarithromycin used with lansoprasole and amoxicillin in eradication regimens for Helicobacter pylori infection. Wien Klin Wochenschr 116: 495–499
Megraud F (2003) Surveillance de la resistance de Helicobacter pylori aux antibiotiques. Surveillance nationale des maladies infectieuses 1998–2000. Institute de Veille Sanitaire, St. Maurice, France, pp 327–329
Gupta VK, Dhar A, Srinivasan S, Rattan A, Sharma MP (1997) Eradication of H. pylori in a developing country: comparison of lansoprazole versus omeprazole with nor-floxacin, in a dual therapy study. Am J Gastroenterol 92: 1140–1142
Ahuja V, Dhar A, Bal C, Sharma MP (1998) Lanzoprazole and secnidazole with clarithromycin, amoxicillin or pefloxacin in the eradication of Helicobacter pylori in a developing country. Aliment Pharmacol Ther 12: 551–555
Cheon JH, Kim N, Lee DH, Kim JM, et al (2006) Efficacy of moxifloxacin-based triple therapy as second-line treatment for Helicobacter pylori infection. Helicobacter 11: 46–51
Von Keutz E, Schluter G (1999) Preclinical evaluation of moxifloxacin, a novel fluoroquinolone. J Antimicrob Chemother 43 [Suppl B]: 91–100
Nightingale CH (2000) Moxifloxacin, a new antibiotic designed to treat community-acquired respiratory tract infections: a review of microbiologic and pharmacokinetic-pharmacodynamic characteristics. Pharmacotherapy 20: 245–256
Blondeau JM, Laskowiski R, Bjarnason J, et al (2000) Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms. Int J Antibicrob Agents 14: 45–50
Tankovic J, Lascols C, Sculo Q, et al (2003) Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pylori. Antibicrob Agents Chemother 47: 3942–3944
Boyanova L, Mentis A, Gubina M, et al (2002) The status of antimicrobial resistance of Helicobacter pylori in Eastern Europe. Clin Microbiol Infect 8: 388–396
Cellini L, Grande R, Di Campli E, et al (2006) Analysis of genetic variability, antimicrobial susceptibility and virulence markers in Helicobacter pylori identified in Central Italy. Scand J Gastroenterol 41: 280–287
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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 119, 372–378 (2007). https://doi.org/10.1007/s00508-007-0807-2
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DOI: https://doi.org/10.1007/s00508-007-0807-2