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11.01.

2012

Guidelines for Treatment of Helicobacter P lori (printer-friendl )

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G ideline fo T ea men of Helicobacter p lori in he Ea and We
Michael Selgrad; Jan Bornschein; Peter Malfertheiner Posted: 01/01/2012; Expert Rev Anti Infect Ther. 2011;9(8):581-588. © 2011 Expert Reviews Ltd.

Abstract and Introduction
Abstract

Infection with Helicobacter p lori remains a major healthcare burden, with persistently high prevalence rates, especially in less-developed countries. H. p lori infection is causally related to non-malignant and malignant gastroduodenal diseases, such as peptic ulcer diseases, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. Current international guidelines recommend a standard triple therapy as first-line therapy, including a proton pump inhibitor and a combination of amoxicillin and clarithromycin. Standard triple therapy has shown a decreasing efficacy over the years. The main reason is the increasing antibiotic resistance, particular to clarithromycin of H. p lori strains. Several new treatment options or modifications of already established regimens have been introduced to overcome treatment failure. In this article, we intend to report the reasons for treatment failure, and furthermore we give an overview of new treatment options as alternatives to the current treatment regimens. Finally, the strategy for the future is considered.
Introduction

Treatment of Helicobacter p lori infection has become a challenge in recent years. The reasons for this are numerous, but the increasing antibiotic resistance to H. p lori is the single most important factor. Various mechanisms and causes besides H. p lori resistance can explain the loss of efficacy of the proton pump inhibitor (PPI) triple regimen. These include the duration of therapy, rapid metabolization of PPI because of (CYP)2C19 polymorphisms with insufficient control of gastric pH and a consequent reduction in the antibiotic efficacy. This is of high importance in clinical practice, because, for example Asian individuals have a higher proportion of poor metabolizers as compared with the rest of the population(20 vs 5%).[1] Further aspects that negatively affect treatment success are an increase in BMI and smoking.[2,3] However, the most important reason for treatment failure remains the dramatic increase of antibiotic resistance. The primary concern is clarithromycin resistance, which shows a good correlation between bacterial resistance to clarithromycin and eradication failure. The critical bar for clarithromycin resistance is 15 20%, at which clarithromycin loses its efficacy as the most potent individual antibiotic in first-line treatment regimen. The prevalence of H. p lori resistance to clarithromycin in different countries ranges from 2 up to more than 20%.[4] The variations in clarithromycin resistance in various regions of the world are summarized in Table 1. Thus, triple therapy containing clarithromycin without prior susceptibility testing should be abandoned when the clarithromycin resistance rate is over 15 20% in the specific region (Table 1).[5]
Table 1. Overview of primar clarithrom cin resistances around the world.

Countr Germany Sweden Italy Bulgaria
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Patients (n) Year of stud 271 333 255 828 1996 1997 1998 2001 2004 2006 1996 2004

Resistance rates (%) Ref. 3.3 1.5 16.9 18.4 [54] [55] [56] [57]
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2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) Poland UK USA Chile USA China Japan India Malaysia 130 1310 106 50 348 157 1257 67 120 2001 2004 2000 2005 2000 2001 2007† 1993 1996 2006† 2002 2005 2000 2001 2005 2007 2003 2005 2009† 2004† 2000 2009 15 8.3 12.7 12. Countr Germany Sweden Italy Bulgaria Poland UK USA Chile USA China Japan India Malaysia Patients (n) Year of stud 271 333 255 828 130 1310 106 50 348 157 1257 67 120 1996 1997 1998 2001 2004 2006 1996 2004 2001 2004 2000 2005 2000 2001 2007† 1993 1996 2006† 2002 2005 2000 2001 2005 2007 2003 2005 2009† 2004† 2000 2009 Resistance rates (%) Ref. Overview of primar clarithrom cin resistances around the world.7 12.2 20 12.8 10.7 0 3.6 0 37.9 18. 3.3 13.medscape.8 10.11.3 13.3 1.7 0 3.2 20 12.4 15 8.01. 180 50 374 Table 1.2 [58] [59] [35] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] South Korea 65 Taiwan Ethiopia China †Year of publication.5 16.5 27.6 18.5 27.6 18.com/viewarticle/754321_print 180 50 374 .2 [54] [55] [56] [57] [58] [59] [35] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] 2/13 South Korea 65 Taiwan Ethiopia China www.3 12.6 0 37.

This meta-analysis yielded relative risks (RRs) for eradication of 1. to overcome clarithromycin resistance.96. there have been reports showing a considerable increase in tetracycline resistance.73 0. Interestingly. However. Sequential treatment is a new quadruple therapy. with a RR of 0.9] However. the increased length of therapy only results in a modest or insignificant rate of treatment success. and in the remaining 5 days the remnant strains are eliminated by the triple therapy.84.10) for 7-day compared with 10-day triple therapy and 1. Comparing 7-day and 10-day therapy. and levofloxacin as a substitute to clarithromycin in PPI triple therapies.[12] The extension of length of therapy may not be cost effective and concerns need to be raised about decreased compliance and the possibility of more side effects. the 14-day regimen only confers a limited advantage.05 (95% CI: 1. Various methods have been proposed to solve this challenge: extension of the duration of PPI clarithromycin-based triple therapies. The sequential therapy has now been evaluated in various randomized trials and therapeutic success was confirmed overall with respect to the standard triple therapy.79 (95% CI: 0. This may be related to higher www.com/viewarticle/754321_print 3/13 .01).[11] Finally.[6.[11. clarithromycin-resistant strains get eradicated by PPI amoxicillin therapy.11.89. A recent meta-analysis including 21 studies from all over the world compared 7. 95% CI: 0.[8. The current challenge in H.7] Amoxicillin. Sequential & Concomitant Therap The sequential therapy originally introduced and extensively studied in Italy has constantly demonstrated higher eradication rates than the conventional triple therapy. not fully published trial from Korea found no superiority of the sequential therapy compared with standard triple therapies. adopted treatment regimens should have been proven to have an efficacy of more than 90% eradication success in the specific region. as mentioned previously.[15] This regimen provides high eradication rates (>90%) in various countries and continents around the world. the extension of the PPI-clarithromycin based triple therapy to 14 days slightly improves the eradication success and can be considered in specific clinical situations. The eradication rates were 73 and 78%.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) †Year of publication.12) for 7-day compared with 14-day therapy. it must be noted that it may not work in all geographic areas as a recent.medscape. the eradication rates were 77 and 81%. rifampicin and tetracycline remain virtually unaffected by resistance problems.14] However. p < 0.07 (95% CI: 1. consisting of 10-day treatment in which a PPI plus amoxicillin is given for 5 days followed by a PPI plus clarithromycin and a nitroimidazole (metronidazole or tinidazole) for another 5 days. In general.and 14-day treatments. but also shows regional differences. this approach of the sequential therapy may even work in areas of high clarithromycin resistance. none of the meta-analyses found significant differences regarding the rate of side effects with the different durations. It has been reported that metronidazole resistance shows a wide range from 8 up to 80%. p = 0. a recent meta-analysis including 26 studies was presented at the Digestive Disease Week 2010. with a much higher prevalence in developing countries. This study has yielded very similar results.01. but this does not seem to impact on treatment results. Within the first 5 days of therapy. respectively. p lori treatment is therefore. although not always in controlled trials. sequential therapy. Taken together.0001) for 14-day therapy with an improvement of eradication rates of approximately 6%.13.71 0.[10] These findings underline the importance of local measurements and monitoring of antibiotic resistance rates to adapt treatment regimens on local requirements and resistance rates. Standard PPI Triple Therapies & E tension of the Length of PPI-based Triple Therapies Extended 14-day triple therapy has been proposed to overcome the decreasing eradication rates that are achieved with 7-day triple therapy. Metronidazole resistance has remained constant over the years. quadruple therapies.[16] However.02 1. respectively. The improvement of cure rates for 10 days of triple therapy was 4%. A similar benefit was seen with 10 days of treatment compared with 7 days (RR: 0.01 1. With the exception of some studies from the USA.

The quadruple therapy yielded higher eradication rates compared with standard triple therapy.22] With application of this regimen the treatment could even be shortened to 5 days. has been introduced by a Chinese study. Australia and some European countries. Concomitant therapy is a quadruple regimen that contains all four compounds of the sequential regimen and all medications are given together. the sequential therapy is a promising therapeutic approach.[21] Several studies in various countries have proven its efficacy with eradication rates above 90%. Several studies have proven the efficacy of quadruple therapy as second-line and/or salvage therapy.[5] The efficacy of the quadruple therapy as first-line therapy has been proven very recently in a randomized. 10 days of treatment with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium.[23] Quadruple Therap The original quadruple therapy based on omeprazole. Furthermore.[5] Quinolones (Levoflo acin/Mo iflo acin) as a Substitute for Clarithrom cin in PPI Triple Therapies www. Furthermore. the 10-day sequential therapy has shown eradication rates of approximately 80% in areas with a high prevalence of clarithromycin resistant strains. A simplification of the sequential therapy represents the so-called concomitant therapy. previous studies demonstrated significantly lower eradication rates with the metronidazole-based regimen compared with the tinidazole-based regimen. the safety and tolerability of the quadruple therapy was similar to standard therapy.[17] Recently. But these adverse events do not occur commonly and it can be stated that bismuth for the treatment of H. amoxicillin and clarithromycin (standard therapy).medscape. Importantly.[29. In this study.[20] To date.[19] Interestingly.25] Bismuth-containing quadruple therapy should be considered as the best first-line empirical treatment in areas of high clarithromycin resistance. This therapy seemed to be more efficient than PPI triple therapy. Thus. the study further demonstrated that the efficacy of the quadruple therapy does not seem to be affected by either metronidazole or clarithromycin resistance.01.11. but for a general recommendation of sequential therapy or its quadruple variation as a first-line treatment. open-label.[27] A new quadruple regimen adding bismuth potassium citrate to the standard triple therapy. it has to be concluded that quadruple therapy should be considered as the first-line therapy in areas with a high prevalence of clarithromycinresistant H. metronidazole and tetracycline (quadruple therapy) has been compared with 7 days of omeprazole. metronidazole and tetracycline has been proven to be superior to standard triple therapy. Interestingly. studies from multicenter.30] The main problem of the quadruple regimen is the administration of four drugs in a complex scheme and possibly decreased compliance. noninferiority. bismuth subcitrate. such as Japan. with eradication rates constantly higher than 80%.[20. bismuth salts are not available in some countries.[24. clarithromycin and amoxicillin. Interestingly. Phase III trial.com/viewarticle/754321_print 4/13 . The reason for this is the claim of side effects associated with the medication. p lori is safe and well tolerated.[26] Eradication rates were 80% in the quadruple therapy group versus 55% in the standard therapy group.[18] A recent study from Thailand showed similar results. It should be noted that the galenic formulation of three drugs with antibacterial activity provides more consistent results [24 26] than the loose combination of these drugs used in several other studies. this therapy regimen was equal to sequential therapy in one study. the increase of therapy duration from 10 to 14 days does not seem to improve the eradication rates.[28] An important indication for the bismuth-containing quadruple therapy is its use as an empirical second-line therapy after failure of PPI. multiregion randomized trials are needed. p lori strains.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) rates of dual resistance in this area. clarithromycin-based triple therapy. including PPI. and combined with the addition of bismuth and prolongation of the treatment from 7 to 14 days allowed it to overcome clarithromycin resistance in 84% of the patients.

p lori eradication therapy do not vary a lot in different www. Nista and colleagues demonstrated eradication rates of up to 92% in the moxifloxacinbased triple regimens compared with a maximum effect of 79% in the clarithromycin-based regimens.[5. the eradication rates observed in the study by Romano et al.39] After the failure of second-line therapies.4% PPI-AC vs 80.11. as recommended in the current European guidelines.1%) with levofloxacin 500 mg twice-daily sequential therapy.46).8% (95% CI: 92. and there is evidence that a dose of 800 mg per day is superior to the 400 mg standard dose. with the need to optimize dosage and duration of treatment.80. Another opportunity for the application of levofloxacin in the eradication therapy has been demonstrated by a recent study from Romano and colleagues. PPI-AL was superior as the second-line therapy when compared with PPI-AC as second-line therapy.[32. when resistance rates were reported to be approximately 6% in the general population.7% was observed and many countries all over the world have levofloxacin resistance rates of approximately 15% or higher. as well as between different geographic locations.[35] Treatment for 10 days should be preferred over a 7-day course. However. 95% CI: 0.8% (95% CI: 72.0 99. This metaanalysis also revealed fewer side effects and adverse events using levofloxacin-based triple therapy. data is accumulating on the efficacy and tolerability of moxifloxacin-based regimens in the use of H.6% in 2004 up to 28.and second-line treatments for H.33] More recently. After the failure of recommended firstline therapies. the first clinical trials evaluating the efficacy of moxifloacin were performed approximately 10 years ago.01. The prevalence of the infection varies greatly between developing and industrialized countries. moxifloxacin-based triple therapy takes its role as an efficient and well-tolerable second-line treatment.43 48] The indications for the initiation of H. Thus.1% PPI-AL).94 3. levofloxacin was applied as a substitute for clarithromycin in the known sequential therapy regimen.9 98.e..0% (95% CI: 90.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) The increasing prevalence of clarithromycin resistance as mentioned previously has prompted authors to incorporate levofloxacin in triple therapy. especially when compared with bismuth-containing quadruple therapy. But it must be noted that in this study. levofloxacin) cannot randomly be replaced and selected as first-line treatment. seem to be difficult to replicate in areas with a high levofloxacin resistance rate. A total of 375 therapy-naive patients were included in the study and randomized to either 'classical' sequential therapy or sequential regimen containing levofloxacin instead of clarithromycin. rising rates of levofloxacin resistance should be taken into account and it has to be noted that quinolone resistance is often associated with resistances to metronidazole and clarithromycin. However.8 87. p lori infection. levofloxacin-based and clarithromycin-based triple therapies were compared as first. The efficacy of levofloxacin-based triple therapy has been proven in a meta-analysis comparing this regimen with quadruple therapy as salvage therapy.37] Today. rescue therapy should be guided by antimicrobial resistance testing whenever possible.7%) with levofloxacin 250 mg twice-daily sequential therapy. compared with 80.com/viewarticle/754321_print 5/13 .2% in 2008. Clarithromycin-based triple therapy (PPI-AC) achieved a higher eradication rate than levofloxacin-based triple therapy (PPI-AL) as the first-line treatment (87. p lori.[5] E pert Commentar H.[40 42] Over the past years several guidelines have formulated recommendations for treatment indications and different treatment regimens for various clinical scenarios caused by H.[34] However. The authors suggested that levofloxacin-containing sequential therapy is a therapy option as a first-line regimen in areas with clarithromycin resistance rates of more than 15%. p lori infection remains one of the most challenging infectious diseases of the world causing high morbidity and mortality. The eradication rates were 96. a low levofloxacin resistance rate of 3.[38.medscape. A recent study from Korea has reported a steady increase from 5. in patients who experienced failure with the standard triple as first-line therapy.3%) with clarithromycin sequential therapy in the intention-to-treat analysis. p lori eradication therapy. PPI-AL can be recommended.[36.[18] In their trial. The overall eradication rate with the levofloxacin regimen was 81 versus 70% with the quadruple combination (odds ratio: 1. In a recent crossover study. 96.[31] This study underlined the importance that the antibiotics that are currently used as rescue medications (i.

Grade of recommendation A A B B B A A A n. p lori resistance is considered to be the most important factor for treatment failure. Level of evidence 1a 1c 2a 3b 3b 1a 1a 1b n. p lori resistance.com/viewarticle/754321_print . n. p lori eradication rates have declined consistently and even with the recommended regimens. which shows great variety even within individual societies. p lori test and treat in case of unexplained iron deficiency anemia H. H.i. Table 2.d. including complicated peptic ulcer disease) MALToma Atrophic gastritis After gastric cancer resection First-degree relatives of patients with gastric cancer Appropriate in case of investigated nonulcer dyspepsia Helicobacter p lori test and treat in case of uninvestigated dyspepsia (except for regions with low H.) Clarithromycin Duration of Special aspects treatment (da s) Alternative first-line regimen Ref.[5. which is not an acceptable rate. Over the last decade. p lori prevalence) Valuable option in chronic NSAID users but insufficient to prevent NSAIDrelated ulcer disease completely H. The problem that we are currently facing is that successful eradication using a standard triple regimen recommended as the first-line regimen is often not achieved.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) guidelines and are summarized according to the Maastricht III consensus report in Table 2.m.m. Recommendations for Helicobacter p lori eradication according to the results of the Maastricht III consensus conference. but faces increasing rates of failure.: Not mentioned. n. The reason for the different eradication success rates in different areas of the world can be attributed mainly to H.43 48] Table 3. p lori eradication by different clinical societies and their guidelines based on a PPI combined with clarithromycin and amoxicillin and/or metronidazole continues to be the first-line option around the globe (Table 3). In populations with less than 15 20% 6/13 www.medscape.m. n.m. Recommendations taken from [10].01. H. p lori test and treat in case of idiopathic thrombocytopenic purpura MALToma: Mucosa-associated lymphoid tissue lymphoma.m.49] The current standard triple therapy as recommended for H.[4.11. p lori treatment failure is often seen in approximately 20% or more of patients. Stud ( ear) Region First-line regimen PPI (standard dose b. H. Recommendation for Helicobacter p lori eradication Duodenal/gastric ulcer (active or not. Standard Helicobacter p lori eradication therapies and alternative treatment regimens as recommended b different clinical societies and their guidelines.

d. bismuth. metronidazole) [48] Chey e al.) Clarithromycin (200 400 mg 7 b. bismuth. 10 14 days) [44] Asaka e al.) Pacific Amoxicillin 7 region (1000 mg b.i.d. tetracycline.11.i.d. tetracycline. (2007) USA Replacement of amoxicillin by metronidazole with respect to local resistance rates and individual allergic predisposition Bismuth-containing quadruple therapy (PPI.i. 10 14 days) [5] Depending on regional resistance levels.i.) or metronidazole (500 mg b.) PPI (standard dose b. metronidazole.i.i.com/viewarticle/754321_print 7/13 .d. tetracycline.medscape. (2009) (500 mg Europe b.) or metronidazole (400 mg b.) clarithromycin resistance. (2005) PPI Clarithromycin 14 Amoxicillin In populations with less than 15 20% clarithromycin resistance. (2010) Japan PPI (standard dose b.i.d. Amoxicillin can be replaced by metronidazole if less than 40% resistance Bismuth-containing quadruple therapy (PPI. bismuth.d. either clarithromycin or amoxicillin can be replaced by metronidazole Bismuth-containing quadruple therapy (PPI.) Clarithromycin (500 mg Asiab.) Amoxicillin 10 14 (1000 mg b. metronidazole.i.) PPI (standard dose b.) or metronidazole (400 mg b.i. Amoxicillin can be replaced by metronidazole if less than 40% resistance Bismuth-containing quadruple therapy (PPI.d.01.) Metronidazolecontaining triple therapy is not recommended as first-line treatment Sequential therapy is discussed as option of choice (days 1 5: PPI + amoxicillin. (2007) Fock e al.i. 10 14 days) [46] Bourke/Jones Canada e al. bismuth. metronidazole.) Clarithromycin (500 mg b.i.i.i.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) Malfertheiner e al.d.) Amoxicillin (750 mg b.i.d. tetracycline.d.) PPI (standard dose b. [43] day 6 10: PPI + clarithromycin + 5nitroimidazole) www.d.d.) (Maastricht 7 14 Amoxicillin III) (1000 mg b.d.i.d.d.

Southern America. In the case of H.9 18.d.3 13.4 15 8.11. The best strategy to face antimicrobial resistance is to use a proven antibiotic regimen with the right dosage and treatment duration.) Metronidazole should be preferred over amoxicillin if resistance rates are less than 40% for the reason of better tolerability and efficacy Bismuth-containing quadruple therapy (PPI. bismuth. Clarithromycin-resistance varies throughout the world. tetracycline.: Twice daily. Although standard triple therapy does not significantly benefit from the prolongation of treatment duration. Overview of primar clarithrom cin resistances around the world.) (at least) Amoxicillin 7 (1000 mg b.01.[50] Table 1.i.2 20 12.d. overcoming clarithromycin-resistance is the main challenge. 3. metronidazole) or sequential therapy (days 1 5: PPI + amoxicillin.i. some parts of the USA.com/viewarticle/754321_print . days 6 10: PPI + clarithromycin + imidazole-derivative) [47] b. Therefore. The frequent use of antibiotics and their frequent overuse has lead to a steadily increasing rate of antimicrobial resistance.medscape.8 [54] [55] [56] [57] [58] [59] [35] [60] [61] [62] [63] [64] [65] [66] 8/13 South Korea 65 www. p lori.3 1. Five.5 27. (2009) Germany Clarithromycin (500 mg b.i.5 16.6 18.7 12.) or metronidazole (400 mg b. Japan and China (Table 1). Countr Germany Sweden Italy Bulgaria Poland UK USA Chile USA China Japan India Malaysia Patients (n) Year of stud 271 333 255 828 130 1310 106 50 348 157 1257 67 120 1996 1997 1998 2001 2004 2006 1996 2004 2001 2004 2000 2005 2000 2001 2007† 1993 1996 2006† 2002 2005 2000 2001 2005 2007 2003 2005 Resistance rates (%) Ref. the development of new molecular tests that allow the easy detection and monitoring of the antibiotic resistance in various geographical areas will become essential for a timely change in the first-line treatment choices and local adaptation of treatment regimens in the various regions.7 0 3.d. PPI: Proton pump inhibitor.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) Fischbach et al.3 12.d. and the highest rates are found in Southern Europe.ear View The challenge for future therapeutic options remains to facilitate the compliance of drug intake and to overcome antibiotic resistance. prolonged therapy beyond 7 days is crucial for the efficacy of quadruple therapy and of all rescue therapies. Antibiotic resistance-based selection of therapy should be used in areas known to already have a prevalence of strains resistant to currently used antibiotics.i.

Gastroenterol. A vaccine for primary prevention would solve most of the current problems. p lori vaccination is feasible and Phase II and III trials with candidate vaccines are eagerly awaited. Obes. Drugs 64. Basis for the management of drug-resistant Helicobacter p lori infection. Zagari RM. 25. Giorgio F. Worldwide H. 19. Despite the large body of evidence in the animal setting that vaccination against H. The main reason for failure of eradication is H. Surg.01. Saniee P. Abdullahi M.com/viewarticle/754321_print 9/13 . 113 130 (2006). Malfertheiner P. Matsuo K. quadruple therapy. The challenge and goal for the future is the development of a safe and effective vaccine. Malfertheiner P. 177 187 (2010). 8. The infection with H. 553 562 (2007). Suzuki T. Arch. Meta-analysis: duration of first-line protonpump inhibitor based triple therapy for Helicobacter p lori eradication. 180 50 374 2009† 2004† 2000 2009 10. sequential therapy. Magrini N. Cheng FC. Hassan C et al. Capoccia D et al. levofloxacin-based triple or quadruple therapy. Intern. Med. so far very few clinical studies have been carried out. Sidebar Ke Issues Helicobacter p loriprevalence shows a wide range. with rates of 80% in developing countries. p lori is achievable. Kandulski A. 24. Gastrointestin. De Francesco V. Med. Massarrat S. 6. Current treatment regimens show decreasing eradication rates. 2. Gut 56. 7. Megraud F. Increase in resistance rates of H. 409 414 (2010). Malfertheiner P.medscape. O'Morain C et al. 10. Gastroenterol. 9.11. Sheykholeslami A. Siavoshi F. References 1. Dig. Cavallaro LG. Fuccio L. Latifi-Navid S. 26. Most of the protective H. The eradication of Helicobacter p lori is affected by body mass index (BMI). 13. J. 18. 4. Selgrad M. Selgrad M. p lori for a prophylactic or even therapeutic use is badly needed. Grilli D. www. 217 224 (2006). p lori-derived antigens have already been administered to humans and have proven their safety and immunogenicity. Curr. Bazzoli F. Am. Ann. p loricauses high morbidity and mortality worldwide. 618 623 (2010). Di MF. Ong GB. 11.[51 53] This suggests that H.6 0 37. Iran. Liver Dis. Helicobacter p lori: diagnosis and treatment. p loriresistant strains. Scarpignato C. Dis. Ito H et al. 5. 119. Clinical studies have failed to succeed for different reasons. Megraud F. 'Rescue' therapies for the management of Helicobacter p lori infection. 827 832 (1997). 1893 1904 (2004). Med. 1450 1454 (2008). 772 781 (2007). Maximum acid output to graded doses of pentagastrin and its relation to parietal cell mass in Chinese patients with duodenal ulcer. Gut 18.2 [67] [68] [69] A safe and effective vaccine against H.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) Taiwan Ethiopia China †Year of publication. p lori antibiotic resistance: a systematic review. 549 556 (2009). Lam SK. New treatment options include: extension of the length of proton pump inhibitor-based triple therapies. Opin. Helicobacter p lori infection and current clinical areas of contention. p lori isolates to metronidazole and tetracycline comparison of three 3-year studies. 147. 3. Minardi ME. Opin. Annibale B. Smoking increases the treatment failure for Helicobacter p lori eradication. Curr. Current concepts in the management of Helicobacter p lori infection: the Maastricht III Consensus Report. J.

randomized. 99 107 (2004). 562 567 (2003). Sun Q. three-antibiotic. Aliment. •• This study was designed to evaluate the sequential therapy as first-line therapy in Thailand. non-bismuthcontaining "concomitant therapy" versus triple therapy for Helicobacter p lori eradication. 24. Gene E. 16. and tetracycline given with omeprazole versus omeprazole. Luther J. Sequential therapy or triple therapy for Helicobacter p lori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Fiorini G. Sirimontaporn N. 98. J. Presented at: Digestive Disease Week 2010. Vaira D. 2. 25. Osato M. non-inferiority. Am. Calvet X. Sequential therapy in clarithromycin-sensitive and -resistant Helicobacter p lori based on polymerase chain reaction molecular test. Lancet 377. 14. Kramer JR. Duration of proton-pump inhibitor-based triple therapy for Helicobacter p lori eradication: a meta-analysis. 18. New Orleans. Tumwasorn S. Gastroenterol. Gravina AG et al. Schwartz H. In an area with >15% prevalence of clarithromycin-resistant H.11. Sirimontaporn N. Seven-day therapy for Helicobacter p lori in the United States. Vakil N. Hepatol. Lanza F. Aliment. Chey WD. Mahachai V. a levofloxacin-containing sequential therapy is more effective. Adv. Tumwasorn S. Essa AS. 8. Gastroenterol. Sequential therapy for Helicobacter p lori eradication: the time is now! Therap. Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter p lori eradication: a randomised trial. amoxicillin. Gut 59. Gut 59. • This randomized trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H. Hepatol. Gastroenterol. Hunt R.medscape. 17. Wu DC. Liang X. Pract. p lori strains. Pharmacol. 1465 1470 (2010). Kawashima M et al. Leandro G. Romano M. Am. metronidazole. p lori-infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Treiber G. Vilaichone RK. Sequential and concomitant therapy with four drugs is equally effective for eradication of H p lori infection. and clarithromycin for eradication of Helicobacter p lori in duodenal ulcer patients: a prospective. 3069 3079 (2009). Mahachai V. 4. Bazzoli F. 21. Flores A. Gastroenterol. 825 828 (2011). Schoenfeld PS. •• This article is of considerable interest. High efficacy of 14-day triple therapy-based. 20. Thong-Ngam D. Zheng Q et al. Helicobacter 15. 23. and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised. Moayyedi P.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) 12. J. J. 27. A new quadruple therapy for Helicobacter p lori: influence of resistant strains on treatment outcome. 20. Clin. J. Ther. Fischbach L. Ten-day sequential therapy of Helicobacter p lori infection in Thailand. Should triple therapy for Helicobacter p lori eradication be prescribed for 1 week or 2 weeks? Nat. Hepatol. 15. Vakil N. 233 238 (2010). 769 774 (1999). Triple vs quadruple therapy for treating Helicobacter p lori infection: an updated meta-analysis. Am. 19. 1143 1153 (2010). 105. 18. Pharmacol. Graham DY. Haydee B. Malfertheiner P. Wu JY et al. 543 544 (2003). 104. The levofloxacin-based regimen achieved high eradication rates. North American trial.01. Laine L. Higgins PD. The 10-day sequential treatment for Helicobacter p lori was well tolerated and provided a high eradication rate. Hsu PI. Am. triple therapy for primary treatment of Helicobacter p lori infection: systematic review and meta-analysis of efficacy and tolerability. Aliment. USA. Phase 3 trial. Clin. Ther. metronidazole. Pharmacol. bismuth-containing quadruple therapy for initial Helicobacter p lori eradication. 26. Helicobacter 14. El-Zimaity H. 22. Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate. Gastroenterol. 36 41 (2010). 28. Gastroenterol. 596 597 (2007). equally safe and cost-saving compared to a clarithromycin-containing sequential therapy. 13. Thong-Ngam D. Vakil N. 26. LA. J. Empiric quadruple vs. Ther. Helicobacter p lori eradication with a capsule containing bismuth subcitrate potassium. Spenard J. Di MF. Graham DY. Meta-analysis: four-drug. multicenter. 1071 1075 (2010). Okada M. 13. Delchier JC et al. Vaira D. Helicobacter p lori treatment in the era of increasing antibiotic resistance. 105. Gatta L. open-label. 109 118 (2009). Cuomo A. Barth J. Gastroenterol. Nishimura H. Gastroenterol. Azagra R. www.com/viewarticle/754321_print 10/13 . Hassan C. 65 73 (2010). Moayyedi P. 905 913 (2011). Nguyen B. Zullo A. Vakil N. 317 322 (2009). Gisbert JP. 1 5 May 2010.

36. moxifloxacin. 110 114 (2010). Gastroenterol. Chey WD. Grossi L.1136/gut. Gastroenterol.com/viewarticle/754321_print 11/13 . 21. American College of Gastroenterology guideline on the management of Helicobacter p lori infection. 572 578 (2010). Graham DY. 1084 1088 (1991). Zocco MA et al. 39. Dig. 35. Bourke B.231233 (2010) (Epub ahead of print). 021/001. Zullo A. Belosic-Halle Z et al. Seroepidemiology of Helicobacter p lori infection in India. Schneider-Brachert W. 44.11. Pharmacol. Fock KM. 7-days moxifloxacin based therapy for the eradication: a randomized controlled trial. Am. 547 551 (2002). Moxifloxacin-based strategies for first-line treatment of Helicobacter p lori infection. One-week once-daily triple therapy with esomeprazole. Helicobacter 15. 42. Hsu PI.233015 (2010) (Epub ahead of print). 36. Ther. 102. Takahashi S et al. Gastroenterol. J. De Francesco V. Am. Comparison of developing and developed countries. Clin.medscape. Fischbach W. p lori infection. AWMF-registration-no. Caselli M. Wong BC. Vaira D. 13 (2010). Kato M. 32. Z. 399 408 (2005). Epidemiol. Kim N. Aliment. Majstorovic K.01. Dore MP. 69 74 (2008). J. Second-line treatment for Helicobacter p lori infection: 10-day moxifloxacinbased triple therapy versus 2-week quadruple therapy. Taylor DN. J. Marzio L Efficacy of four different moxifloxacinbased triple therapies for first-line H. J. 47. 9. Yoon H. society for pediatric gastroenterology and nutrition e. Liver Dis. Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter p lori infection. www. 782 789 (2007). 47. Kirsch C et al. Sequential therapy for Helicobacter p lori eradication: is levofloxacin better? Gut DOI:10. Clin. Lin JT. Miehlke S. Sacco F. Gastroenterol. Dis.2010. Chiba N et al. 46. 31. Lai KH et al. Kang JM. Gisbert JP. 37. Microbiol. Helicobacter 13. Asaka M. 479 486 (2010). 77 85 (2009). 45. Liver Dis. 34. 33. 1230 1263 (2009). Levofloxacin-based and clarithromycin-based triple therapies as first-line and second-line treatments for Helicobacter p lori infection: a randomised comparative trial with crossover design. 43. Spezzaferro M. 1808 1825 (2007). 857 860 (2002). Maconi G et al. Molina-Infante J. Nista EC. Ceponis P. Graham DY. Levofloxacin in first-line eradication regimens for Helicobacter p lori: better test antibiotic susceptibility before treating. Antimicrob. 25. 1 20 (2010). Mele R et al. Manzoli L. 34. Canadian Helicobacter Study Group Consensus Conference: update on the approach to Helicobacter p lori infection in children and adolescents an evidence-based evaluation. Lee BH et al. Sci. V. Guidelines for the management of Helicobacter p lori infection in Japan: 2009 revised edition. Gut DOI:10. p lori to the outcome of 10-days vs. 38. Lee DH et al. 39. S3-guideline "Helicobacter p lori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology. Candelli M. 97. 41.1136/gut. Reddy GT et al. Gastroenterol. Gut 59. German society for rheumatology. J. 623 628 (2007). • This article is of interest. Malfertheiner P. Moxifloxacin-containing triple therapy as second-line treatment for Helicobacter p lori infection: effect of treatment duration and antibiotic resistance on the eradication rate. Amitrano M. The strategy of using clarithromycin as the initial treatment and levofloxacin as the rescue regimen achieved higher eradication rates than the reverse sequence. • This study aimed to asses the efficacy of a levofloxacin-based regimen as the first-line treatment and a clarithromycin-based regimen as the second-line treatment for H. 19. and rifabutin for eradication of persistent Helicobacter p lori resistant to both metronidazole and clarithromycin. Adam E. Blaser MJ The epidemiology of Helicobacter p lori infection. but not as the second-line treatment. Lin CK.. Hoffmann JC et al. 40. Rev. The clarithromycin-based regimen achieved a higher eradication rate than the levofloxacin-based regimen as the first-line treatment.2010. Can. Gastroenterol. p lori treatment. Chang CY et al. 42 59 (1991). Helicobacter 12. Ang TL Epidemiology of Helicobacter p lori infection and gastric cancer in Asia. Helicobacter 14. "Cervia II Working Group Report 2006": guidelines on diagnosis and treatment of Helicobacter p lori infection in Italy. Dig. Bago J. 42. One-week quadruple therapy is an effective salvage regimen for Helicobacter p lori infection in patients after failure of standard triple therapy. 13. Liou JM. Antimicrobial resistance of H. Hepatol. 30. Ann. Zullo A.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) 29. Kim N. Dig. 1241 1247 (2005).

Helicobacter 15. Am. Teare EL. 57. Antimicrobial susceptibility of Helicobacter p lori strains in a random adult Swedish population. for molecular detection of antibiotic resistance in Helicobacter p lori. 47. Cheng H. Ronkainen J et al. Eur. 63. Perna F. 15. Kim CH et al. Prevalence of Helicobacter p lori resistance to several antimicrobial agents in a region of Germany. Ethiopia. Prevalence of metronidazole. Rosenkranz B et al. 17. 66. Yang HB. Chattopadhyay S. Hepatol. Datta S. Hepatol. Institutional difference of antibiotic resistance of Helicobacter p lori strains in Korea. p lori vaccine demonstrated satisfactory safety and immunogenicity. Pharmacol. Sugano K et al. Clin. Gastroenterol. Malfertheiner P. Vakil N. 65. Antimicrobial susceptibility pattern of Helicobacter p lori strains isolated from adult dyspeptic patients in Tikur Anbassa University Hospital. 52. E pert. 1037 1049 (2009). Ahmad N. 1587 1600 (2009). 22. genotype HelicoDR. Asrat D. Coulon C et al. 24. 787 795 (2008). World J. Euro Surveill. Wadstrom T. Med. Helicobacter 11. Addis Ababa. Zullo A. Ther. China. J.medscape. Development of vaccines against Helicobacter p lori. 56. Fock KM. produced antigen-specific T-cell memory and therefore. Primary antibiotic resistance in Helicobacter p lori strains isolated in northern and central Italy. clarithromycin and tetracycline resistance in Helicobacter p lori isolated from Chilean patients. 93. Celinska-Cedro D et al. 1230 1235 (2009). 51 57 (2005). Aliment. 54. Kobayashi I. Patra R et al. The evolution of Helicobacter p lori antibiotics resistance over 10 years in Beijing. J. Garrido L. 50. Boyanova L. Wu JJ. 65 68 (2006). Gastroenterolog 135. Nikolov R. 61.01. Lazarova E et al. Cheng HC. Gastroenterol. Nilius M. Kim JM. 1432 1435 (1998). Microbiol. Gastroenterol. J. Clin. Vallejos C. Infect. Gastroenterol. Rev. Microbiol. Chil. Storskrubb T. Cambau E. Malfertheiner P. Sheu BS. J. Ther. Surveillance of primary antibiotic resistance of Helicobacter p lori at centres in England and Wales over a six-year period (2000 2005). Allerheiligen V. Li J. Antibacterial resistance in Helicobacter p lori strains isolated from Bulgarian children and adult patients over 9 years. Med. 683 687 (2006). 287 293 (2007). 40. 62. Dis. •• This study evaluated the safety and immunogenicity of an H. Davies K. www. Leodolter A. Chisholm SA. Aro P. 69. Hu FL. Muller WA. 60. Aliment. 135. Chang WL. 79 85 (2004). 51. Dzierzanowska-Fangrat K. J.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) 48. Caceres D et al. Characterization of clarithromycin resistance in Malaysian isolates of Helicobacter p lori. Nat. Del GG. Zakaria WR. Mengistu Y. Yang YJ.com/viewarticle/754321_print 12/13 . 4006 4010 (2007). 25. Helicobacter p lori and antibiotic resistance. Rev. J. Cheng H. 12. 2679 2682 (2006). Owen RJ. Gut 56. Hu F et al. Abdullah SA. warrants further clinical study. Gastroenterol. 67. Vaccinating against Helicobacter p lori infection. 224 230 (2006). Rozynek E. 133 140 (2011). 58. Hahn B. Blanchard T. 55.11. Murakami K. Hassan C et al. Second Asia-Pacific Consensus Guidelines for Helicobacter p lori infection. Antimicrobial resistance of Helicobacter p lori in Poland: a multicentre study. J. Clin. Safety and immunogenicity of an intramuscular Helicobacter p lori vaccine in noninfected volunteers: a Phase I study. Evaluation of a new test. 59. 68. Malfertheiner P. Vaccines 8. Schultze V. Megraud F. J. Mohamed R. Ethiop. clarithromycin and levofloxacin of Helicobacter p lori before and after clarithromycin-based therapy in Taiwan. 45. Pharmacol. 3161 3165 (2009). Konig W. 460 466 (2010). Microbiol. 55. Influence of resistance of Helicobacter p lori to antibiotics on the Helicobacter p lori eradication regimens. Kassa E. Most Helicobacter p lori strains of Kolkata in India are resistant to metronidazole but susceptible to other drugs commonly used for eradication and ulcer therapy. 24. 3600 3607 (2009). Agents 26. 49. Wolle K. 8. The intramuscular H. E3 E4 (2007). Kim N. Nilsson I. Gao W. Gastroenterol. Rappuoli R. Resistance to metronidazole. Changing antimicrobial susceptibility epidemiology of Helicobacter p lori strains in Japan between 2002 and 2005. 519 521 (1998). Zhonghua Yi Xue Za Zhi 86. Med. 53. 230 234 (2005). 64. Microbiol. J. Rev. p lori vaccine. Clin. 42. Int. Czinn SJ. Antimicrob. J. 1502 (2007). Hepatol. 1429 1434 (2007). Clarithromycin-resistant Helicobacter p lori in patients with duodenal ulcer in the United States. Kato M et al. Katelaris P. McSorley D.

The authors have no other relevant affiliations or financial involvement w ith any organization or entity w ith a financial interest in or financial conflict w ith the subject matter or materials discussed in the manuscript apart from those disclosed.9(8):581-588. Novartis Vaccine and Nycomed.01.2012 Guidelines for Treatment of Helicobacter P lori (printer-friendl ) Papers of special note have been highlighted as: • of interest •• of considerable interest Financial & com pe ing in e e di clo e Peter Malfertheiner has affiliations w ith Aptalis. 2011.11. www. No w riting assistance w as utilized in the production of this manuscript.medscape.com/viewarticle/754321_print 13/13 . Expert Rev Anti Infect Ther. 2011 Expert Review s Ltd.