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DOI: 10.1055/s-0031-1273390
© Georg Thieme Verlag KG Stuttgart · New York
Aktueller Stellenwert von Fluorchinolonen in der Helicobacter-pylori-Therapie
Current Value of Quinolones in Helicobacter pylori TherapyPublication 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.
Schlüsselwörter
Erstlinientherapie - Helicobacter pylori - Levofloxacin - Moxifloxacin - Sitafloxacin - Fluorchinolon-Resistenz
Key words
first-line therapy - Helicobacter pylori - levofloxacin - moxifloxacin - sitafloxacin - quinolone-resistance
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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 7
Megraud F.
H pylori antibiotic resistance: prevalence, importance, and advances in testing.
Gut.
2004;
53
1374-1384
MissingFormLabel
- 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
MissingFormLabel
- 9
De Sarro A, De Sarro G.
Adverse reactions to fluoroquinolones. An overview on mechanistic aspects.
Curr Med Chem,.
2001;
8
371-84
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 13
Glocker E, Stueger H P, Kist M.
Quinolone resistance in Helicobacter pylori isolates in Germany.
Antimicrob Agents Chemother.
2007;
51
346-349
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 33
Rispo A, Di Girolamo E, Cozzolino A et al.
Levofloxacin in first-line treatment of Helicobacter pylori infection.
Helicobacter.
2007;
12
364-365
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 52
Suzuki H, Nishizawa T, Saito Y et al.
Sitafloxacin-based third-line eradication of H. pylori.
Gastroenterol.
2010;
(DDW abstract)
MissingFormLabel
- 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)
MissingFormLabel
- 54
Berning M, Krasz S, Miehlke S.
Should quinolones come first in Helicobacter pylori therapy?.
Ther Adv Gastroenterol.
2011;
4
103-114
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 60
Graham D Y, Fischbach L.
Helicobacter pylori treatment in the era of increasing antibiotic resistance.
Gut.
2010;
59
1143-1153
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
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