Published online May 21, 2014. doi: 10.3748/wjg.v20.i19.5654
Revised: November 29, 2013
Accepted: February 20, 2014
Published online: May 21, 2014
Processing time: 232 Days and 19.3 Hours
Standard triple therapy, consisting of a proton pump inhibitor, plus amoxicillin and clarithromycin, has been the most commonly used first-line treatment regimen for Helicobacter pylori (H. pylori) eradication for many years worldwide. However, as a result of increased resistance to antibiotics, H. pylori eradication rates with use of standard triple therapy have been declining and recently reached < 80% in many countries. Several new strategies to enhance the eradication rate of H. pylori have been studied. Currently, among the alternative first-line eradication regimens, concomitant and hybrid regimens have shown excellent results and could be the optimal treatment option. Although clinical usefulness of rescue therapy for patients in whom eradication of H. pylori with non-bismuth quadruple regimen has failed is unclear, levofloxacin-based quadruple therapy has shown promise as a rescue treatment. The choice of third-line therapy depends on factors such as the local pattern of antibiotic resistance, drug availability, and previous treatment. We hope that a simple method for detection of antibiotic susceptibility using polymerase chain reaction would be a possible alternative to administration of “tailored treatment” in the era of increasing prevalence of antimicrobial resistance.
Core tip: Currently, among the alternative first-line eradication regimens, concomitant and hybrid regimens have shown excellent results and could be the optimal treatment option. Levofloxacin-based quadruple therapy has shown promise as a rescue treatment.
-
Citation: Heo J, Jeon SW. Optimal treatment strategy for
Helicobacter pylori : Era of antibiotic resistance. World J Gastroenterol 2014; 20(19): 5654-5659 - URL: https://www.wjgnet.com/1007-9327/full/v20/i19/5654.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i19.5654
Helicobacter pylori (H. pylori) is an important factor worldwide influencing progression from chronic gastritis to peptic ulcer and gastric cancer[1]. Nowadays, the incidence of H. pylori infection has shown a declining trend. In Korea, in a survey of 5732 asymptomatic patients in 1998, the seropositive rate of H. pylori infection was reported as 66.9% in adults[2]. However, it had declined to 59.6% in 2005[3]. The main cause of this difference is treatment for H. pylori infection.
Triple therapy, consisting of a proton pump inhibitor (PPI), plus amoxicillin and clarithromycin, was accepted by the international guidelines in 1996 and has been the most commonly used first-line treatment regimen for H. pylori eradication in most countries for many years[4,5]. According to Graham et al[6], the treatment regimen that meets the category of Grade A [intention-to-treat (ITT) cure rate is 95%-100%] should be prescribed as a therapeutic regimen for H. pylori infection. Regimens scoring as B (ITT cure rate 90%-95%) can be used if Grade A is not obtainable. Unfortunately, H. pylori eradication rates with standard triple therapy have been declining and recently reached < 80% in many countries[6].
This phenomenon has been largely related to an increase in bacterial resistance to antibiotics, particularly against clarithromycin[7]. In Japan, resistance to clarithromycin increased from 19% to 28% during 2002-2005[8]. In Korea, a study of 652 isolates from 1994 to 1999 found that resistance to metronidazole and clarithromycin increased from 33% to 48% and 4.8% to 7.7%, respectively[9]. Another recent survey reported that resistance to clarithromycin increased from 16.7% to 38.5% during 2003-2005 and 2007-2009 in Korea[10].
Several strategies to enhance the eradication rate of H. pylori have been studied and ongoing results are anticipated. The aim of this review is to suggest timely suitable approaches to management of patients with H. pylori infection.
There was a simple question regarding whether longer duration of standard triple therapy could result in a higher rate of eradication. In a multicenter study conducted in the US, of 284 patients, the H. pylori eradication rate after triple therapy for 14 d was 85% (96/113), which did not differ from 84% (103/123) reported for triple therapy for 10 d[11]. In another study comparing 3-, 7- and 10-d triple therapies with rabeprazole to a 10-d omeprazole control triple therapy, no statistically significant difference was observed between the 7-d rabeprazole-based regimen (77%) and 10-d rabeprazole-based regimen (78%) and omeprazole-based regimen (73%)[12]. In a meta-analysis of the duration of triple therapy, relative risk for eradication was reported as 1.05 (95%CI: 1.01-1.10) for 7-d compared with 10-d triple therapy and 1.07 (95%CI: 1.02-1.12) for 7-d compared with 14-d therapy[13]. Thus, currently, extending the duration of triple therapy beyond 7 d did not show a marked benefit. Other regimens with longer duration have shown promise and are discussed below.
Bismuth-containing quadruple therapy has been proven as a salvage therapy regimen for failure of standard triple therapy in many countries[14,15]. The regimen consists of PPI, bismuth, tetracycline and metronidazole. However, regarding the first-line therapy, recent results have been disappointing. In a large study, bismuth-containing quadruple therapy [ITT, 82%; per-protocol (PP), 88%] did not show superior eradication rate compared with standard triple therapy (ITT, 78%; PP, 82%)[16]. In a meta-analysis of bismuth-containing quadruple therapy with standard triple therapy [nine randomized controlled trials (RCTs), n = 1679], bismuth quadruple therapy achieved an eradication rate similar to that of primary therapy for H. pylori infection compared with standard triple therapy (78.3% vs 77.0%, RR = 1.002, 95%CI: 0.936-1.073)[17].
In a recent RCT, the new combination of bismuth containing 2 wk quadruple therapy, including bismuth, PPI, amoxicillin, and clarithromycin, achieved an eradication rate of 90.7% as a first-line treatment[18]. In another RCT, quadruple therapy with moxifloxacin and bismuth showed an eradication rate of 92%[19]. Although conduct of additional studies is needed to validate these results, these studies imply that another bismuth-containing regimen could be an alternative option as a first-line treatment.
In a meta-analysis of the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapy for H. pylori[20], clarithromycin resistance had a greater effect on treatment efficacy than nitroimidazole resistance. Metronidazole resistance reduced efficacy by 26% in triple therapies containing nitromidazole, tetracycline and bismuth, while efficacy was reduced by only 14% when a gastric acid inhibitor was added to the regimen. Quadruple therapies containing both clarithromycin and metronidazole were the most efficacious; > 80% eradication rate for H. pylori infection. Therefore, non-bismuth, three-antibiotic-containing quadruple therapies, consisting of PPI, amoxicillin, clarithromycin and nitroimidazole, could be the key as a new standard first-line regimen.
Sequential therapy: Sequential therapy was introduced as a novel therapeutic approach for H. pylori eradication by Zullo et al[21,22] in 2000. Ten-day sequential therapy regimen consists of 5 d of dual treatment with a PPI plus amoxicillin, followed by 5 d of triple treatment with a PPI, clarithromycin and nitromidazole. Zullo et al[22] reported eradication rates for sequential therapy of 92% by ITT and 95% by PP analysis. Since then, many studies have reported a superior result of sequential therapy compared with standard triple therapy[23,24]. In two meta-analyses of RCTs, sequential therapy showed an association with a higher eradication rate of H. pylori at 91%-93.4%, compared with standard triple regimen at 75.7%-76.9%[25,26]. However, these RCTs were conducted before 2008. In recent studies, the success rate of the sequential regimen appeared to be lower, compared to previous trials. In 10 recent RCTs on sequential therapy during 2008-2012, the eradication rate was 80.6% (95%CI: 78.5%-82.7%) for sequential therapy compared to 75.8% (95%CI: 73.5%-78.1%) for standard triple therapy[27]. Theoretically, the objective during the first 5 d of taking amoxicillin is to disrupt the cell wall of H. pylori and to prevent activation of efflux channels. Therefore, this damage to the cell wall could help to improve the efficacy of clarithromycin in the sequential phase of treatment[28,29]. However, there is a conflicting opinion against this theory. The main role of sequential therapy may be related to use of large numbers of antibiotics, including nitroimidazole, not the sequential administration itself[30,31]. In addition, there is a problem with sequential therapy, which is that taking the medication is relatively complex for patients. The patient is required to switch from a dual to a triple regimen[32], which may reduce the compliance of patients and result in a decrease in eradication rates in patients with multiple antibiotic resistance in clinical practice.
In this regard, the triple combination of antibiotics such as clarithromycin plus amoxicillin and a nitroimidazole with PPI has been highlighted or has re-emerged as a non-sequential regimen - concomitant therapy.
Concomitant therapy: In a systemic review reported by Essa et al[32], which included nine studies, concomitant therapy achieved an eradication rate of 89.7% in ITT and 92.9% in PP. In a meta-analysis of 15 studies (1723 patients), a significantly higher eradication rate was achieved with concomitant therapy, compared to standard triple therapy (90%, 95%CI: 86%-93%)[33]. A tendency towards better results with longer treatments (7-10 d vs 3-5 d) was observed. In our interim analysis of multicenter RCTs (six institutes, 214 patients in ITT analysis, unpublished), the eradication rate of the 10-d concomitant therapy group was significantly higher than that of the 10-d standard triple therapy group (89.3% vs 79.3%, P = 0.049).
Both sequential therapy and concomitant therapy have shown superiority over legacy triple therapy, especially in cases of clarithromycin resistance. Clarithromycin resistance is the result of different point mutations, which have a different therapeutic impact on current regimens. In a systematic review of sequential therapy, the eradication rate was reported as 75% (41/55, four studies) in clarithromycin-resistant strains[34]. However, the effect of clarithromycin resistance on the efficacy of concomitant regimens was negligible, with 95% efficacy in the clarithromycin-sensitive arm, and 96% in the clarithromycin-resistant arm[20]. In addition, in another study, concomitant therapy was found to be more suitable for patients with dual antibiotic resistances than sequential therapy[35].
Hybrid therapy (sequential-concomitant therapy): Hybrid therapy is a combination of sequential therapy and concomitant therapy. Hybrid therapy regimens consist of PPI and amoxicillin for 10-14 d, with addition of clarithromycin and metronidazole for the final 5-7 d. In a recent study, this regimen showed excellent results, with an eradication rate of 99.1% (95%CI: 97.3%-100%) by PP and 97.4% (95%CI: 94.5%-100%) by ITT analysis[36]. This study is meaningful for achievement of Grade A treatment success for H. pylori infection. In another recent RCT (n = 343) for comparison with concomitant therapy, the rates of eradication for hybrid and concomitant therapies were 92% (95%CI: 87%-95%) and 96.1% (95%CI: 93%-99%), respectively (P = 0.07)[37]. In that study, 23.5% of patients had H. pylori strains that were resistant to clarithromycin, and 8.8% were resistant to clarithromycin and metronidazole. This antimicrobial resistance did not impair the efficacy of either of the non-bismuth quadruple regimens. However, larger sample size and conduct of studies in other countries is needed in order to validate the effectiveness of hybrid therapy.
Data from RCTs for the first-line non-bismuth-containing quadruple therapies are provided in Table 1[35,37-42].
Author | Country | Publication year | Therapy regimen | Patients (n) | Eradication rate (ITT) | |
Wu et al[35] | Taiwan | 2010 | S | E 40 mg bd + AMX 1 g bd for 5 d followed by | 115 | 92.3% |
E 40 mg bd + CLA 500 mg bd + MET 500 mg bd for 5 d | ||||||
C | E 40 mg bd + AMX 1 g bd + CLA 500 mg bd + MET 500 mg bd for 10 d | 117 | 93.0% | |||
Huang et al[38] | Taiwan | 2012 | S | L 30 mg bd + AMX 1 g bd for 5 d followed by | 85 | 80.0% |
L 30 mg bd + CLA 500 mg bd +MET 500 mg bd for 5 d | ||||||
C | L 30 mg bd + AMX 1 g bd + CLA 500 mg bd + MET 500 mg bd for 10 d | 84 | 88.1% | |||
McNicholl et al[39] | Spain | 2013 | S | O 20 mg bd + AMX 1 g bd for first 5 d followed by | 170 | 81% |
O 20 mg bd + CLA 500 mg bd + MET 500 mg bd for 5 d | ||||||
C | O 20 mg bd + AMX 1 g bd + CLA 500 mg bd + MET 500 mg bd for 10 d | 168 | 87% | |||
Lim et al[40] | Korea | 2013 | S | R 20 mg bd + AMX 1 g for 7 d followed by | 86 | 75.6% |
R 20 mg bd + CLA 500 mg bd + MET 500 mg bd for 7 d | ||||||
C | R 20 mg bd + AMX 1 g bd + CLA 500 mg bd + MET 500 mg bd for 14 d | 78 | 80.8% | |||
Zullo et al[41] | Italy | 2013 | S | O 20 mg qd + AMX 1 g qd 5d followed by | 90 | 91.1% |
O 20 mg qd + CLA 500 mg qd + TIN 500 mg qd for 5 d | ||||||
C | O 20 mg qd + AMX 1 g qd + CLA 500 mg qd + TIN 500 mg qd for 5 d | 90 | 85.5% | |||
H | O 20 mg qd + AMX 1 g qd for 14 d plus | 90 | 80.0% | |||
CLA 500 mg qd + TIN 500 mg qd for last 7 d | ||||||
Sardarian et al[42] | Iran | 2013 | S | P 40 mg bd + AMX 1 g bd for 5 d followed by | 210 | 76.7% |
P 40 mg bd + CLA 500 mg bd + TIN 500 mg bd for 5 d | ||||||
H | P 40 mg bd + AMX 1 g bd for 14 d plus | 210 | 89.5% | |||
CLA 500 mg bd + TIN 500 mg bd for last 7 d | ||||||
Molina-Infante et al[37] | Spain, Italy | 2013 | C | O 40 mg bd + AMX 1 g bd + CLA 500 mg bd + NIT 500 mg bd for 14 d | 172 | 91.7% |
H | O 40 mg bd + AMX 1 g bd for 14 d plus | 171 | 90.0% | |||
CLA 500 mg bd + TIN 500 mg bd for last 7 d |
After failure of a PPI-clarithromycin-containing regimen, bismuth-containing quadruple therapy is recommended by the Maastricht IV guidelines[43]. In three studies of bismuth-containing quadruple therapy as second-line therapy, eradication rates of 55%-69.1% have been reported[44-46]. In a recent study conducted in Korea, higher eradication rates were reported for 2-wk bismuth-containing quadruple therapy compared with the same regimen for 1 wk (64.3% vs 82.6%, ITT analysis, P = 0.002)[47]. However, these data were regarding the rescue therapy after failure of standard triple therapy. Data regarding rescue therapy after failure of non-bismuth-containing quadruple therapy as a first-line treatment are insufficient[48].
The Maastricht IV guidelines recommend levofloxacin-based triple therapy containing PPI and amoxicillin as a rescue treatment in areas of high clarithromycin resistance[43]. The eradication rate of levofloxacin 500 mg with PPI and amoxicillin was 60%-85% after two eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline[49,50]. However, the recommended regimen had a somewhat disappointing eradication rate as a rescue treatment after failure of sequential or concomitant treatment, below 80%[51,52]. In addition, the rapid acquisition of resistance to levofloxacin may be a problem in future efficacy. In fact, a recent study reported a high prevalence of levofloxacin resistance (29.5%) in H. pylori strains isolated from Korean patients[10]. Therefore, a new combination regimen is warranted. In a recent study conducted in Taiwan, 10-d quadruple therapy containing PPI, bismuth, tetracycline, and levofloxacin achieved an excellent result, with an eradication rate of 95.8% after failure of first-line treatment with sequential therapy[53]. This new combination of levofloxacin-based quadruple therapy is expected as the second-line therapy and validation of other combinations with levofloxacin is needed. In addition, high dose of levofloxacin (750 mg), which achieved a better effect against infectious disease[54], should be validated for H. pylori eradication. In summary, although further validation is needed, levofloxacin-based quadruple therapy is a promising rescue regimen after failure of first-line non-bismuth-containing quadruple therapy.
After failure of second-line treatment, antimicrobial susceptibility testing is needed by obtaining gastric biopsy specimens for culture. In general, the method of agar dilution is needed for H. pylori susceptibility testing. However, culture and susceptibility testing require specific equipment, which is not available in most medical centers. In a recent study, Helicobacter genotype and the CYP2C19 polymorphism were examined for detection of antimicrobial resistance[55]. In addition, a new method using polymerase chain reaction (PCR) has been validated for detection of resistance of H. pylori to clarithromycin[56]. It is a simple method and requires a shorter time than culture. However, further validation and study for use of a PCR method in real treatment are needed. In the near future, a new tailored regimen for individual patients would be the answer to antibiotic resistance.
As a result of increased resistance to antibiotics, conventional triple therapy is no longer standard therapy for naïve H. pylori infection. Currently, among the alternative first-line eradication regimens, concomitant and hybrid regimens have shown excellent results and could be the optimal treatment option. After failure of new first-line non-bismuth quadruple treatment, levofloxacin- based quadruple regimens could be an option for rescue treatment. In addition, we hope that development of a simple method for detection of antimicrobial resistance before H. pylori eradication and a new tailored treatment for H. pylori will be possible in the near future.
P- Reviewers: Iera E, Shimatani T, Slomiany BL S- Editor: Gou SX L- Editor: Kerr C E- Editor: Liu XM
1. | Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347:1175-1186. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1848] [Cited by in F6Publishing: 1839] [Article Influence: 83.6] [Reference Citation Analysis (3)] |
2. | Kim JH, Kim HY, Kim NY, Kim SW, Kim JG, Kim JJ, Roe IH, Seo JK, Sim JG, Ahn H. Seroepidemiological study of Helicobacter pylori infection in asymptomatic people in South Korea. J Gastroenterol Hepatol. 2001;16:969-975. [PubMed] [Cited in This Article: ] |
3. | Yim JY, Kim N, Choi SH, Kim YS, Cho KR, Kim SS, Seo GS, Kim HU, Baik GH, Sin CS. Seroprevalence of Helicobacter pylori in South Korea. Helicobacter. 2007;12:333-340. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 207] [Cited by in F6Publishing: 200] [Article Influence: 11.8] [Reference Citation Analysis (0)] |
4. | Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56:772-781. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1348] [Cited by in F6Publishing: 1304] [Article Influence: 76.7] [Reference Citation Analysis (1)] |
5. | Fock KM, Katelaris P, Sugano K, Ang TL, Hunt R, Talley NJ, Lam SK, Xiao SD, Tan HJ, Wu CY. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol. 2009;24:1587-1600. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 384] [Cited by in F6Publishing: 405] [Article Influence: 27.0] [Reference Citation Analysis (1)] |
6. | Graham DY, Lu H, Yamaoka Y. A report card to grade Helicobacter pylori therapy. Helicobacter. 2007;12:275-278. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 244] [Cited by in F6Publishing: 296] [Article Influence: 17.4] [Reference Citation Analysis (0)] |
7. | Mégraud F. H pylori antibiotic resistance: prevalence, importance, and advances in testing. Gut. 2004;53:1374-1384. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 607] [Cited by in F6Publishing: 658] [Article Influence: 32.9] [Reference Citation Analysis (1)] |
8. | Kobayashi I, Murakami K, Kato M, Kato S, Azuma T, Takahashi S, Uemura N, Katsuyama T, Fukuda Y, Haruma K. Changing antimicrobial susceptibility epidemiology of Helicobacter pylori strains in Japan between 2002 and 2005. J Clin Microbiol. 2007;45:4006-4010. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 119] [Cited by in F6Publishing: 130] [Article Influence: 7.6] [Reference Citation Analysis (0)] |
9. | Kim JJ, Reddy R, Lee M, Kim JG, El-Zaatari FA, Osato MS, Graham DY, Kwon DH. Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea. J Antimicrob Chemother. 2001;47:459-461. [PubMed] [Cited in This Article: ] |
10. | Hwang TJ, Kim N, Kim HB, Lee BH, Nam RH, Park JH, Lee MK, Park YS, Lee DH, Jung HC. Change in antibiotic resistance of Helicobacter pylori strains and the effect of A2143G point mutation of 23S rRNA on the eradication of H. pylori in a single center of Korea. J Clin Gastroenterol. 2010;44:536-543. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 103] [Cited by in F6Publishing: 110] [Article Influence: 7.9] [Reference Citation Analysis (1)] |
11. | Fennerty MB, Kovacs TO, Krause R, Haber M, Weissfeld A, Siepman N, Rose P. A comparison of 10 and 14 days of lansoprazole triple therapy for eradication of Helicobacter pylori. Arch Intern Med. 1998;158:1651-1656. [PubMed] [Cited in This Article: ] |
12. | Vakil N, Lanza F, Schwartz H, Barth J. Seven-day therapy for Helicobacter pylori in the United States. Aliment Pharmacol Ther. 2004;20:99-107. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 111] [Cited by in F6Publishing: 123] [Article Influence: 6.2] [Reference Citation Analysis (0)] |
13. | Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F. Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication. Ann Intern Med. 2007;147:553-562. [PubMed] [Cited in This Article: ] |
14. | Dore MP, Graham DY, Mele R, Marras L, Nieddu S, Manca A, Realdi G. Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection. Am J Gastroenterol. 2002;97:857-860. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 53] [Cited by in F6Publishing: 53] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
15. | Lin CK, Hsu PI, Lai KH, Lo GH, Tseng HH, Lo CC, Peng NJ, Chen HC, Jou HS, Huang WK. One-week quadruple therapy is an effective salvage regimen for Helicobacter pylori infection in patients after failure of standard triple therapy. J Clin Gastroenterol. 2002;34:547-551. [PubMed] [Cited in This Article: ] |
16. | Katelaris PH, Forbes GM, Talley NJ, Crotty B. A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: The QUADRATE Study. Gastroenterology. 2002;123:1763-1769. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 114] [Cited by in F6Publishing: 116] [Article Influence: 5.3] [Reference Citation Analysis (0)] |
17. | Luther J, Higgins PD, Schoenfeld PS, Moayyedi P, Vakil N, Chey WD. Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: Systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol. 2010;105:65-73. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 153] [Cited by in F6Publishing: 150] [Article Influence: 10.7] [Reference Citation Analysis (0)] |
18. | Ergül B, Doğan Z, Sarikaya M, Filik L. The efficacy of two-week quadruple first-line therapy with bismuth, lansoprazole, amoxicillin, clarithromycin on Helicobacter pylori eradication: a prospective study. Helicobacter. 2013;18:454-458. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 15] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
19. | Ciccaglione AF, Cellini L, Grossi L, Marzio L. Quadruple therapy with moxifloxacin and bismuth for first-line treatment of Helicobacter pylori. World J Gastroenterol. 2012;18:4386-4390. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 14] [Cited by in F6Publishing: 18] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
20. | Fischbach L, Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Aliment Pharmacol Ther. 2007;26:343-357. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 246] [Cited by in F6Publishing: 268] [Article Influence: 15.8] [Reference Citation Analysis (0)] |
21. | Zullo A, Rinaldi V, Winn S, Meddi P, Lionetti R, Hassan C, Ripani C, Tomaselli G, Attili AF. A new highly effective short-term therapy schedule for Helicobacter pylori eradication. Aliment Pharmacol Ther. 2000;14:715-718. [PubMed] [Cited in This Article: ] |
22. | Zullo A, Vaira D, Vakil N, Hassan C, Gatta L, Ricci C, De Francesco V, Menegatti M, Tampieri A, Perna F. High eradication rates of Helicobacter pylori with a new sequential treatment. Aliment Pharmacol Ther. 2003;17:719-726. [PubMed] [Cited in This Article: ] |
23. | Park HG, Jung MK, Jung JT, Kwon JG, Kim EY, Seo HE, Lee JH, Yang CH, Kim ES, Cho KB. Randomised clinical trial: a comparative study of 10-day sequential therapy with 7-day standard triple therapy for Helicobacter pylori infection in naïve patients. Aliment Pharmacol Ther. 2012;35:56-65. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 63] [Cited by in F6Publishing: 69] [Article Influence: 5.8] [Reference Citation Analysis (0)] |
24. | Paoluzi OA, Visconti E, Andrei F, Tosti C, Lionetti R, Grasso E, Ranaldi R, Stroppa I, Pallone F. Ten and eight-day sequential therapy in comparison to standard triple therapy for eradicating Helicobacter pylori infection: a randomized controlled study on efficacy and tolerability. J Clin Gastroenterol. 2010;44:261-266. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 39] [Cited by in F6Publishing: 49] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
25. | Jafri NS, Hornung CA, Howden CW. Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Ann Intern Med. 2008;148:923-931. [PubMed] [Cited in This Article: ] |
26. | Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol. 2009;104:3069-3079; quiz 1080. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 195] [Cited by in F6Publishing: 218] [Article Influence: 14.5] [Reference Citation Analysis (0)] |
27. | Zullo A, Hassan C, Ridola L, De Francesco V, Vaira D. Standard triple and sequential therapies for Helicobacter pylori eradication: an update. Eur J Intern Med. 2013;24:16-19. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 48] [Cited by in F6Publishing: 50] [Article Influence: 4.5] [Reference Citation Analysis (0)] |
28. | Murakami K, Fujioka T, Okimoto T, Sato R, Kodama M, Nasu M. Drug combinations with amoxycillin reduce selection of clarithromycin resistance during Helicobacter pylori eradication therapy. Int J Antimicrob Agents. 2002;19:67-70. [PubMed] [Cited in This Article: ] |
29. | De Francesco V, Margiotta M, Zullo A, Hassan C, Troiani L, Burattini O, Stella F, Di Leo A, Russo F, Marangi S. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med. 2006;144:94-100. [PubMed] [Cited in This Article: ] |
30. | Vaira D, Zullo A, Vakil N, Gatta L, Ricci C, Perna F, Hassan C, Bernabucci V, Tampieri A, Morini S. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med. 2007;146:556-563. [PubMed] [Cited in This Article: ] |
31. | Summaries for patients. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication. Ann Intern Med. 2007;146:I20. [PubMed] [Cited in This Article: ] |
32. | Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing “concomitant therapy” versus triple therapy for Helicobacter pylori eradication. Helicobacter. 2009;14:109-118. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 155] [Cited by in F6Publishing: 170] [Article Influence: 11.3] [Reference Citation Analysis (0)] |
33. | Gisbert JP, Calvet X. Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori. Aliment Pharmacol Ther. 2011;34:604-617. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 126] [Cited by in F6Publishing: 121] [Article Influence: 9.3] [Reference Citation Analysis (0)] |
34. | Gisbert JP, Calvet X, O’Connor A, Mégraud F, O’Morain CA. Sequential therapy for Helicobacter pylori eradication: a critical review. J Clin Gastroenterol. 2010;44:313-325. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 118] [Cited by in F6Publishing: 139] [Article Influence: 9.9] [Reference Citation Analysis (0)] |
35. | Wu DC, Hsu PI, Wu JY, Opekun AR, Kuo CH, Wu IC, Wang SS, Chen A, Hung WC, Graham DY. Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol Hepatol. 2010;8:36-41.e1. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 172] [Cited by in F6Publishing: 189] [Article Influence: 13.5] [Reference Citation Analysis (0)] |
36. | Hsu PI, Wu DC, Wu JY, Graham DY. Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days. Helicobacter. 2011;16:139-145. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 125] [Cited by in F6Publishing: 142] [Article Influence: 10.9] [Reference Citation Analysis (0)] |
37. | Molina-Infante J, Romano M, Fernandez-Bermejo M, Federico A, Gravina AG, Pozzati L, Garcia-Abadia E, Vinagre-Rodriguez G, Martinez-Alcala C, Hernandez-Alonso M. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology. 2013;145:121-128.e1. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 139] [Cited by in F6Publishing: 143] [Article Influence: 13.0] [Reference Citation Analysis (0)] |
38. | Huang YK, Wu MC, Wang SS, Kuo CH, Lee YC, Chang LL, Wang TH, Chen YH, Wang WM, Wu DC. Lansoprazole-based sequential and concomitant therapy for the first-line Helicobacter pylori eradication. J Dig Dis. 2012;13:232-238. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 51] [Cited by in F6Publishing: 56] [Article Influence: 4.7] [Reference Citation Analysis (0)] |
39. | McNicholl AG, Marin AC, Molina-Infante J, Castro M, Barrio J, Ducons J, Calvet X, de la Coba C, Montoro M, Bory F. Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice. Gut. 2014;63:244-249. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 94] [Cited by in F6Publishing: 105] [Article Influence: 10.5] [Reference Citation Analysis (0)] |
40. | Lim JH, Lee DH, Choi C, Lee ST, Kim N, Jeong SH, Kim JW, Hwang JH, Park YS, Lee SH. Clinical outcomes of two-week sequential and concomitant therapies for Helicobacter pylori eradication: a randomized pilot study. Helicobacter. 2013;18:180-186. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 68] [Cited by in F6Publishing: 63] [Article Influence: 5.7] [Reference Citation Analysis (0)] |
41. | Zullo A, Scaccianoce G, De Francesco V, Ruggiero V, D’Ambrosio P, Castorani L, Bonfrate L, Vannella L, Hassan C, Portincasa P. Concomitant, sequential, and hybrid therapy for H. pylori eradication: a pilot study. Clin Res Hepatol Gastroenterol. 2013;37:647-650. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 63] [Cited by in F6Publishing: 71] [Article Influence: 6.5] [Reference Citation Analysis (0)] |
42. | Sardarian H, Fakheri H, Hosseini V, Taghvaei T, Maleki I, Mokhtare M. Comparison of hybrid and sequential therapies for Helicobacter pylori eradication in Iran: a prospective randomized trial. Helicobacter. 2013;18:129-134. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 74] [Cited by in F6Publishing: 82] [Article Influence: 7.5] [Reference Citation Analysis (0)] |
43. | Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut. 2012;61:646-664. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1541] [Cited by in F6Publishing: 1514] [Article Influence: 126.2] [Reference Citation Analysis (4)] |
44. | Rokkas T, Sechopoulos P, Robotis I, Margantinis G, Pistiolas D. Cumulative H. pylori eradication rates in clinical practice by adopting first and second-line regimens proposed by the Maastricht III consensus and a third-line empirical regimen. Am J Gastroenterol. 2009;104:21-25. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 89] [Cited by in F6Publishing: 95] [Article Influence: 6.3] [Reference Citation Analysis (0)] |
45. | Lee JM, Breslin NP, Hyde DK, Buckley MJ, O’Morain CA. Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice. Aliment Pharmacol Ther. 1999;13:489-496. [PubMed] [Cited in This Article: ] |
46. | Gisbert JP, Gisbert JL, Marcos S, Jimenez-Alonso I, Moreno-Otero R, Pajares JM. Empirical rescue therapy after Helicobacter pylori treatment failure: a 10-year single-centre study of 500 patients. Aliment Pharmacol Ther. 2008;27:346-354. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 66] [Cited by in F6Publishing: 60] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
47. | Lee BH, Kim N, Hwang TJ, Lee SH, Park YS, Hwang JH, Kim JW, Jeong SH, Lee DH, Jung HC. Bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate in Korea. Helicobacter. 2010;15:38-45. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 88] [Cited by in F6Publishing: 91] [Article Influence: 6.5] [Reference Citation Analysis (0)] |
48. | Shehada S, Srugo I, Shaoul R. Failure of sequential therapy to eradicate Helicobacter pylori in previously treated subjects. Helicobacter. 2007;12:645-647. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 10] [Cited by in F6Publishing: 9] [Article Influence: 0.5] [Reference Citation Analysis (0)] |
49. | Gisbert JP, Gisbert JL, Marcos S, Moreno-Otero R, Pajares JM. Third-line rescue therapy with levofloxacin is more effective than rifabutin rescue regimen after two Helicobacter pylori treatment failures. Aliment Pharmacol Ther. 2006;24:1469-1474. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 70] [Cited by in F6Publishing: 59] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
50. | Gatta L, Zullo A, Perna F, Ricci C, De Francesco V, Tampieri A, Bernabucci V, Cavina M, Hassan C, Ierardi E. A 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses. Aliment Pharmacol Ther. 2005;22:45-49. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 87] [Cited by in F6Publishing: 69] [Article Influence: 3.6] [Reference Citation Analysis (0)] |
51. | Manfredi M, Bizzarri B, de’Angelis GL. Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate. Helicobacter. 2012;17:246-253. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 28] [Cited by in F6Publishing: 33] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
52. | Gisbert JP, Molina-Infante J, Marin AC, Vinagre G, Barrio J, McNicholl AG. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple “sequential” or “concomitant” treatment to eradicate H. pylori infection. Scand J Gastroenterol. 2013;48:652-656. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 28] [Article Influence: 2.5] [Reference Citation Analysis (0)] |
53. | Hsu PI, Chen WC, Tsay FW, Shih CA, Kao SS, Wang HM, Yu HC, Lai KH, Tseng HH, Peng NJ. Ten-day Quadruple therapy comprising proton-pump inhibitor, bismuth, tetracycline, and levofloxacin achieves a high eradication rate for Helicobacter pylori infection after failure of sequential therapy. Helicobacter. 2014;19:74-79. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 30] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
54. | Noreddin AM, Marras TK, Sanders K, Chan CK, Hoban DJ, Zhanel GG. Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia (CAP). Int J Antimicrob Agents. 2004;24:479-484. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 26] [Cited by in F6Publishing: 27] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
55. | Furuta T, Sagehashi Y, Shirai N, Sugimoto M, Nakamura A, Kodaira M, Kenmotsu K, Nagano M, Egashira T, Ueda K. Influence of CYP2C19 polymorphism and Helicobacter pylori genotype determined from gastric tissue samples on response to triple therapy for H pylori infection. Clin Gastroenterol Hepatol. 2005;3:564-573. [PubMed] [Cited in This Article: ] |
56. | Giorgio F, Principi M, De Francesco V, Zullo A, Losurdo G, Di Leo A, Ierardi E. Primary clarithromycin resistance to Helicobacter pylori: Is this the main reason for triple therapy failure? World J Gastrointest Pathophysiol. 2013;4:43-46. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 26] [Cited by in F6Publishing: 31] [Article Influence: 2.8] [Reference Citation Analysis (0)] |