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Shih CA, Shie CB, Tai WC, Chuah SK, Lee HC, Hsu PI. Update on the second-line treatment of Helicobacter pylori infection: a narrative review. Therap Adv Gastroenterol 2023; 16:17562848231192750. [PMID: 37675247 PMCID: PMC10478561 DOI: 10.1177/17562848231192750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 07/20/2023] [Indexed: 09/08/2023] Open
Abstract
A standard bismuth quadruple therapy, a fluoroquinolone-containing triple (or quadruple) therapy or a proton pump inhibitor (PPI)-amoxicillin high-dose dual therapy has been recommended as a second-line treatment for Helicobacter pylori infection by the Maastricht VI/Florence Consensus Report. The major shortcoming of levofloxacin-amoxicillin triple therapy is low cure rate for eradicating levofloxacin-resistant strains. With the rising prevalence of levofloxacin-resistant strains, levofloxacin-amoxicillin triple therapy cannot reliably achieve a high eradication rate for second-line treatment of H. pylori infection in most countries now. The present article aims to review current second-line eradication regimens with a per-protocol eradication rate exceeding 85% in most geographic areas. Recently, a novel tetracycline-levofloxacin quadruple therapy consisting of a PPI, bismuth, tetracycline, and levofloxacin for rescue treatment of H. pylori infection has been developed. The new therapy achieved a higher per-protocol eradication rate than levofloxacin-amoxicillin triple treatment in a randomized controlled trial (98% versus 69%). Additionally, the tetracycline-levofloxacin quadruple therapy also exhibits a higher eradication rate than amoxicillin-levofloxacin quadruple therapy. High-dose dual PPI-amoxicillin therapy is another novel second-line treatment for H. pylori infection. The new therapy can achieve an eradication rate of 89% by per-protocol analysis for the second-line treatment in Taiwan. Recently, levofloxacin-based sequential quadruple therapy and potassium-competitive acid blocker have also been applied in the second-line treatment of H. pylori infection. A meta-analysis revealed that a vonoprazan-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. In conclusion, the eradication rate of levofloxacin-amoxicillin triple therapy is suboptimal in the second-line treatment of H. pylori infection now. Currently, a standard bismuth quadruple therapy (tetracycline-metronidazole quadruple therapy), a tetracycline-levofloxacin quadruple therapy, an amoxicillin-levofloxacin quadruple therapy, a levofloxacin-based sequential quadruple therapy or a high-dose PPI-amoxicillin dual therapy is recommended for the second-line treatment of H. pylori infection.
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Affiliation(s)
- Chih-An Shih
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung County
- Department of Nursing, Meiho University, Pingtung County
| | - Chang-Bih Shie
- Division of Gastroenterology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan
| | - Wei-Chen Tai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, and Chang Gung University College of Medicine, Taoyuan
| | - Seng-Kee Chuah
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, and Chang Gung University College of Medicine, Taoyuan
| | - Hsi-Chang Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Renai Branch, Taipei City Hospital, 10, Section 4, Ren’ai Road, Da’an District 106, Taipei
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, No. 66, Sec. 2, Changhe Road., Annan Dist., Tainan City 70965
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Losurdo G, D'Abramo FS, Piazzolla M, Rima R, Continisio A, Pricci M, Ierardi E, Di Leo A. Second-line Therapy for Helicobacter Pylori Eradication: State of the Art. Mini Rev Med Chem 2022; 22:2430-2437. [PMID: 35339174 DOI: 10.2174/1389557522666220325153832] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 01/04/2022] [Accepted: 01/12/2022] [Indexed: 01/10/2023]
Abstract
Helicobacter pylori (H. pylori) is a Gram negative spiraliform bacterium that colonizes the human stomach. It is the most common cause of chronic gastritis, peptic ulcer, and gastric carcinoma. The eradication therapy is based on the combination of a proton pump inhibitor and several antibiotics such as amoxicillin, metronidazole, clarithromycin, levofloxacin or tetracycline. The most commonly used regimens for eradication in the first line are triple, sequential and concomitant therapy, despite the last European Guidelines suggesting a quadruple therapy already at the first attempt in areas with high resistance rates. However, the rise in antibiotic resistance is the main reason for a marked increase in first-line therapy failure. Clarithromycin resistancea, is especially acknowledged as the most important event resulting in failure. Up to 20% of patients are intended not to eradicate, therefore they will need a second line therapy. Currently, the most used rescue regimens are levofloxacin-based triple therapy and bismuth-containing quadruple therapy, despite guidelines suggesting to use a combination of antibiotics that have not been included in previous treatments. Nitazoxanide is a novel antibiotic with promising results. Additionally, an interesting field worth of investigation is the antibiotic susceptibility based approach, which could help choose antibiotics with confirmed effectiveness in vitro. Analysis of antibiotic resistance may be performed by both bacterial culture and molecular biology techniques, able to detect point mutations conferring resistance. This is a particularly interesting approach, since it may personalize the therapy, thus optimizing the regimen and maximizing the probability of success.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
- PhD Course in Organs and Tissue Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
| | - Fulvio Salvatore D'Abramo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
| | - Mariapaola Piazzolla
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
| | - Raffaella Rima
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
| | - Antonio Continisio
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
| | | | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University "Aldo Moro" of Bari, 70124 Bari, Italy
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Nestegard O, Johnsen KM, Sørbye SW, Halvorsen FA, Tønnessen T, Paulssen EJ, Melby KK, Goll R, Florholmen J. Clinical characterization of Helicobacter pylori infected patients 15 years after unsuccessful eradication. PLoS One 2020; 15:e0238944. [PMID: 32966303 PMCID: PMC7510978 DOI: 10.1371/journal.pone.0238944] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 08/26/2020] [Indexed: 01/03/2023] Open
Abstract
Background and aims Patients that have failed therapy for Helicobacter pylori (H. pylori) infection are incompletely characterized. The aim of this study was to characterize a H. pylori treatment resistant cohort compared to the cohorts of newly diagnosed, earlier eradicated and non-infected. Material and methods Patients were selected from routine referrals to the Endoscopy units at three different Norwegian hospitals. In all four cohorts, gastric biopsies were scored according to the Sydney classification, and symptoms according to the Gastrointestinal Symptom Rating Scale score, including sub-scores for upper gastrointestinal symptoms and functional bowel symptoms. Patients in the H. pylori resistant group were treated with a triple therapy regimen that consisted of levofloxacin, amoxicillin and a proton pump inhibitor. Results We included 185 patients, 42 H. pylori treatment resistant, 50 newly diagnosed, 61 previously H. pylori eradicated and 32 never infected. The treatment-resistant cohort had higher scores for upper gastrointestinal symptoms and functional bowel symptoms compared to the other groups except for the group being never H. pylori infected. The H. pylori resistant patients had lower Sydney scores than patients with newly diagnosed H. pylori infection. The triple combination showed a high efficacy of 91% to eradicate H. pylori. Conclusions Patients with treatment-resistant H. pylori infection had more gastrointestinal symptoms, but a lower Sydney score than patients with newly diagnosed infection. A treatment regimen including levofloxacin showed a high efficacy in eradicating H. pylori in patients that previously had failed eradication treatment.
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Affiliation(s)
- Oddmund Nestegard
- Department Gastroenterology, Vestre Viken Hospital, Hønefoss, Norway
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
- * E-mail:
| | - Kay-Martin Johnsen
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
| | - Sveinung W. Sørbye
- Department of Pathology, University Hospital of North Norway, Tromsø, Norway
| | | | - Tor Tønnessen
- Department Gastroenterology, Vestre Viken Hospital, Drammen, Norway
| | - Eyvind J. Paulssen
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
| | - Kjetil K. Melby
- Department of Microbiology, University Hospital Oslo and University of Oslo, Oslo, Norway
| | - Rasmus Goll
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
| | - Jon Florholmen
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
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Lin TF, Hsu PI. Second-line rescue treatment of Helicobacter pylori infection: Where are we now? World J Gastroenterol 2018; 24:4548-4553. [PMID: 30386104 PMCID: PMC6209570 DOI: 10.3748/wjg.v24.i40.4548] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 09/20/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
At present, the best rescue therapy for Helicobacter pylori (H. pylori) infection following failure of first-line eradication remains unclear. The Maastricht V/Florence Consensus Report recommends bismuth quadruple therapy, or fluoroquinolone-amoxicillin triple/quadruple therapy as the second-line therapy for H. pylori infection. Meta-analyses have shown that bismuth quadruple therapy and levofloxacin-amoxicillin triple therapy have comparable eradication rates, while the former has more adverse effects than the latter. There are no significant differences between the eradication rates of levofloxacin-amoxicillin triple and quadruple therapies. However, the eradication rates of both levofloxacin-containing treatments are suboptimal. An important caveat of levofloxacin-amoxicillin triple or quadruple therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. High-dose dual therapy is an emerging second-line therapy and has an eradication efficacy comparable with levofloxacin-amoxicillin triple therapy. Recently, a 10-d tetracycline-levofloxacin (TL) quadruple therapy comprised of a proton pump inhibitor, bismuth, tetracycline and levofloxacin has been developed, which achieves a markedly higher eradication rate compared with levofloxacin-amoxicillin triple therapy (98% vs 69%) in patients with failure of standard triple, bismuth quadruple or non-bismuth quadruple therapy. The present article reviews current second-line anti-H. pylori regimens and treatment algorisms. In conclusion, bismuth quadruple therapy, levofloxacin-amoxicillin triple/quadruple therapy, high-dose dual therapy and TL quadruple therapy can be used as second-line treatment for H. pylori infection. Current evidence suggests that 10-d TL quadruple therapy is a simple and effective regimen, and has the potential to become a universal rescue treatment following eradication failure by all first-line eradication regimens for H. pylori infection.
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Affiliation(s)
- Te-Fu Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
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Kwon S, Lee DH, Kang JB, Kim N, Park YS, Shin CM, Yoon H, Choi YJ. [The Efficacy of Bismuth-containing Quadruple Therapy after Moxifloxacin-based Sequential Therapy Failure in Helicobacter pylori Eradication]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 71:196-203. [PMID: 29684968 DOI: 10.4166/kjg.2018.71.4.196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Background/Aims Moxifloxacin-based sequential therapy showed an excellent eradication rate as the first line treatment of Helicobacter pylori (H. pylori) infection. However, to the best of our knowledge, there were only a few studies on the treatment of those with failed moxifloxacin-based sequential therapy. Hence, this study was to investigate the efficacy of bismuth-containing quadruple therapy in those with failed moxifloxacin-based sequential or reverse sequential therapy for H. pylori eradication. Methods Between January 2013 and March 2016, we retrospectively analyzed patients who failed to eradicate H. pylori using moxifloxacin-based sequential (rabeprazole 20 mg bid and amoxicillin 1 g bid for 5-7 days, followed by rabeprazole 20 mg bid, metronidazole 500 mg bid, and moxifloxacin 400 mg qd for 5-7 days) and 10 days moxifloxacin-based reverse sequential therapy as the first line treatment. Then we investigated the eradication rates of bismuth-containing quadruple therapy as the second line treatment. All subjects had no history of H. pylori eradication before. Eradication rates were described as intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori status was evaluated by ¹³C-urea breath test 6 weeks after the end of the treatment. Moreover, we examined any side effects that caused discontinuation of therapy. Results Twenty-three patients received bismuth-containing quadruple therapy as the second line treatment. The overall eradication rates by ITT and PP analyses were 60.87% (n=14/23) and 73.68% (n=14/19). All the patients showed good compliance, and there were no serious adverse events. Conclusions Bismuth-containing quadruple therapy is insufficient as the second line eradication treatment after a failed attempt of moxifloxacin-based sequential or reverse sequential therapy. Large-scale clinical trials should be performed to establish better clinical evidence.
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Affiliation(s)
- Soohoon Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Bin Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Wu TS, Hsu PI, Kuo CH, Hu HM, Wu IC, Wang SSW, Chen YH, Wu DC, Su WW, Kuo FC. Comparison of 10-day levofloxacin bismuth-based quadruple therapy and levofloxacin-based triple therapy for Helicobacter pylori. J Dig Dis 2017; 18:537-542. [PMID: 28644575 DOI: 10.1111/1751-2980.12498] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 06/01/2017] [Accepted: 06/20/2017] [Indexed: 01/10/2023]
Abstract
OBJECTIVE This was a prospective study aiming to investigate whether levofloxacin plus bismuth-based quadruple therapy was more effective than levofloxacin-based triple therapy after failed first-line eradication therapies for Helicobacter pylori (H. pylori) infection. METHODS Sixty-seven patients infected with H. pylori were randomly assigned to two groups; the levofloxacin plus bismuth-based quadruple therapy group (RBAL [n = 33]; rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days) and the levofloxacin-based triple therapy group (RAL [n = 34]; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days). Endoscopy was performed 4-8 weeks after H. pylori eradication to assess treatment response. We followed up patient response and compliance and checked their resistance to antibiotics. RESULTS Intention-to-treat analysis revealed that both groups had similar eradication rates (RBAL vs RAL: 84.8% [95% confidence interval {CI} 72.6-97.1%] vs 67.6% [95% CI 51.9-83.4%], P = 0.0987). No significant differences in compliance or adverse events were found (P = 0.9829 and 0.0720). Epsilometer test showed that most eradication failure cases were levofloxacin-resistant. CONCLUSIONS Adding bismuth subcitrate to levofloxacin-based triple therapy was not more effective than not doing so, but no further side effects were noted. Both eradication therapies were equally safe and patients had the same tolerance to both regimens. Resistance rate to levofloxacin may be important when choosing second-line therapy.
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Affiliation(s)
- Tzung-Shiun Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, China
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan, China
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans' General Hospital and National Yangming University, Kaohsiung, Taiwan, China
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, China
- Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, China
- Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, China
| | - Huang-Ming Hu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, China
- Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, China
| | - I-Chen Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, China
- Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, China
| | - Sophie S W Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, China
| | - Yen-Hsu Chen
- Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, China
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, China
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, China
- Faculty of Medicine, Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, China
- Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, China
- Department of Internal Medicine, Kaohsiung Municipal Tatung Hospital, Kaohsiung, Taiwan, China
| | - Wei-Wen Su
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan, China
| | - Fu-Chen Kuo
- School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, China
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Marin AC, Nyssen OP, McNicholl AG, Gisbert JP. Efficacy and Safety of Quinolone-Containing Rescue Therapies After the Failure of Non-Bismuth Quadruple Treatments for Helicobacter pylori Eradication: Systematic Review and Meta-Analysis. Drugs 2017; 77:765-776. [DOI: 10.1007/s40265-017-0730-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Park SM, Kim JS, Kim BW, Ji JS, Choi H. Randomized clinical trial comparing 10- or 14-day sequential therapy and 10- or 14-day concomitant therapy for the first line empirical treatment of Helicobacter pylori infection. J Gastroenterol Hepatol 2017; 32:589-594. [PMID: 27505301 DOI: 10.1111/jgh.13510] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Whether concomitant therapy is superior to sequential therapy (ST) as first-line therapy of Helicobacter pylori in areas with high clarithromycin resistance remains controversial. The aim of this study was to compare the efficacy and tolerability of 10- or 14-day ST with 10- or 14-day concomitant therapy (CT). METHODS This was a prospective randomized study comparing 10- or 14-day ST with 10- or 14-day CT. The ST-10 and ST-14 groups received pantoprazole 40 mg and amoxicillin 1 g twice a day for the first 5 and 7 days followed by pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500 mg twice a day for the remaining 5 and 7 days, respectively. The CT-10 and CT-14 groups received pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 and 14 days, respectively. RESULTS Three hundred forty-one patients were randomly allocated to the four groups. The modified intention-to-treat eradication rates of ST-10, ST-14, CT-10, and CT-14 were 91.7%, 91.2%, 94.2%, and 98.5%, respectively. The corresponding per protocol eradication rates were 91.4%, 91.0%, 95.6%, and 98.5%. There was no difference in compliance and adverse events in the four groups. Eradication rates increased sequentially with statistical significance in the following order: ST-10, ST-14, CT-10, and CT-14 (P = 0.044). CONCLUSIONS All four regimens achieved eradication rates >90% in per protocol analyses in a country with high clarithromycin resistance. There was no difference in tolerability among the four regimens.
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Affiliation(s)
- Sung Min Park
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Incheon St. Mary's Hospital, Catholic University of Korea, Incheon, Korea
| | - Joon Sung Kim
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Incheon St. Mary's Hospital, Catholic University of Korea, Incheon, Korea
| | - Byung-Wook Kim
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Incheon St. Mary's Hospital, Catholic University of Korea, Incheon, Korea
| | - Jeong-Seon Ji
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Incheon St. Mary's Hospital, Catholic University of Korea, Incheon, Korea
| | - Hwang Choi
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Incheon St. Mary's Hospital, Catholic University of Korea, Incheon, Korea
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Talebi Bezmin Abadi A. Helicobacter pylori treatment: New perspectives using current experience. J Glob Antimicrob Resist 2017; 8:123-130. [PMID: 28131855 DOI: 10.1016/j.jgar.2016.11.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/10/2016] [Accepted: 11/20/2016] [Indexed: 02/08/2023] Open
Abstract
Infection with Helicobacter pylori plays an essential role in the development of duodenal and gastric ulcers as well as in the pathobiology of gastric adenocarcinoma. Thus, successful elimination of the bacterium can reduce the risk of development of these diseases. Currently, most guidelines recommend standard triple therapy (amoxicillin+clarithromycin+proton pump inhibitor), although its efficacy is rapidly falling. Notably, traditional first-line therapy fails in almost 32% of H. pylori-carrying cases, suggesting the importance of choosing the best formulation for first-line therapy. Hence, due to the decreasing effectiveness of first-line treatment, we should be prepared to confront increasing H. pylori therapeutic defeat. Owing to increasing reports of antibiotic resistance worldwide, newer approaches and directions are necessary for managing this problematic infection. Developing and providing better anti-H. pylori strategies (probiotics, antibiotic therapy and non-traditional medicine) without using current clinical experience in treating the infection is impossible. Furthermore, development and examination of new preventive vaccines may also be a new therapeutic direction. Taken together, with regard to current experience, clinicians are highly recommended to consider all alternatives to eradicate H. pylori until a universal vaccine becomes practically available. This article aims to give an overview regarding the current status of H. pylori treatment, accordingly designing an actual overview to gain optimal strategies against this infection.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-111, Tehran, Iran.
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Liou JM, Chen CC, Lee YC, Chang CY, Wu JY, Bair MJ, Lin JT, Chen MJ, Wu MS. Systematic review with meta-analysis: 10- or 14-day sequential therapy vs. 14-day triple therapy in the first line treatment of Helicobacter pylori infection. Aliment Pharmacol Ther 2016; 43:470-81. [PMID: 26669729 DOI: 10.1111/apt.13495] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 10/30/2015] [Accepted: 11/12/2015] [Indexed: 01/30/2023]
Abstract
BACKGROUND Whether 10-day or 14-day sequential therapy is superior to 14-day triple therapy in the first-line treatment of Helicobacter pylori remains controversial. AIM To compare the efficacy of 10-day or 14-day sequential therapy vs. 14-day triple therapy. METHODS Randomised controlled trials (RCTs) comparing 10-day or 14-day sequential therapy and 14-day triple therapy as first-line treatment in adults were searched from the PubMed and Cochrane databases from 2000 to October 2015. Abstracts from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention-to-treat analysis and adverse effects, respectively. RESULTS Of the 109 articles identified, 13 RCTs including 2749 patients in the sequential therapy group and 2424 patients in the 14-day triple therapy group were eligible. Overall, sequential therapy for 10 or 14 days was not significantly superior to 14-day triple therapy [Risk ratio (RR) 1.04, 95% confidence interval (CI) 0.99-1.08, P = 0.145]. However, there was significant heterogeneity (I(2) = 57.6%, P = 0.005). In the subgroup analysis of four trials, we found that 14-day sequential therapy was significantly more effective than 14-day triple therapy (RR: 1.09, 95% CI: 1.04-1.16, P = 0.002), and there was no significant heterogeneity (I(2) = 0%, P = 0.624) in this comparison. Sequential therapy given for 10 days was not superior to 14-day triple therapy (RR: 1.03, 95% CI: 0.98-1.09, P = 0.207). There was no significant difference in the risk of adverse effects. CONCLUSION Sequential therapy given for 14 days, but not 10 days, was more effective than 14-day triple therapy as first-line treatment.
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Affiliation(s)
- J-M Liou
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - C-C Chen
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Y-C Lee
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - C-Y Chang
- Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan
| | - J-Y Wu
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - M-J Bair
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung, Taiwan.,Department of Nursing, Meiho University, Pingtung, Taiwan
| | - J-T Lin
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - M-J Chen
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - M-S Wu
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Yazbek PB, Trindade AB, Chin CM, Dos Santos JL. Challenges to the Treatment and New Perspectives for the Eradication of Helicobacter pylori. Dig Dis Sci 2015; 60:2901-12. [PMID: 25999247 DOI: 10.1007/s10620-015-3712-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 05/07/2015] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current treatment of H. pylori infection with antibiotics and proton pump inhibitors has several limitations, including poor adherence and intrinsic patient-related factors, drug resistance, and the absence of adequate treatments. This review summarizes the current therapeutic approaches to eradicating H. pylori, the difficulties associated with its treatment, and several new perspectives aimed at improving existing treatment strategies.
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Affiliation(s)
- Priscila Baptistella Yazbek
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Ariane Biolcati Trindade
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Chung Man Chin
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Jean Leandro Dos Santos
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil.
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12
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The impact of amalgam dental fillings on the frequency of Helicobacter pylori infection and H. pylori eradication rates in patients treated with concomitant, quadruple, and levofloxacin-based therapies. Eur J Gastroenterol Hepatol 2015; 27:769-75. [PMID: 25919773 DOI: 10.1097/meg.0000000000000372] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIM Mercury exposure is encountered most commonly in individuals with amalgam fillings. The toxic, bactericidal, and immunosuppressive effects of mercury are well known. Furthermore, multiple antibiotic resistance can be transferred, together with mercury resistance. The aim of this study was to investigate the frequency of Helicobacter pylori infection in dyspeptic patients with amalgam fillings and the effect of the amalgam fillings on H. pylori eradication rates in these patients. PATIENTS AND METHODS Four hundred and seventy-five patients who presented with dyspeptic complaints and underwent upper gastrointestinal endoscopy and gastric biopsy were included in this study. One hundred and sixty-nine (35.6%) patients were negative and 306 (64.4%) patients were positive for H. pylori. All of the participants underwent dental examinations in a blinded manner. The participants were divided into two groups on the basis of the presence of amalgam fillings. The H. pylori-positive patients were divided randomly into three subgroups: patients who received concomitant therapy (CT) (rabeprazole-amoxicillin-clarithromycin-metronidazole for 14 days; n=122); patients who received quadruple therapy (QT) (rabeprazole-tetracycline-metronidazole-colloidal bismuth subcitrate for 10 days; n=97); and patients who received levofloxacin-based therapy (LT) (rabeprazole-amoxicillin-levofloxacin for 10 days; n=87). Eradication success was detected by a urea breath test 6 weeks after the end of treatment. RESULTS The frequency of H. pylori infection was significantly lower in the filling group compared with the nonfilling group (53.7 and 78.8%, respectively; P<0.001). The eradication rates in the CT, QT, and LT groups were 65.5, 67.0, and 58.6%, respectively, in the intention-to-treat (ITT) analysis and 69.6, 70.7, and 62.2%, respectively, in the per-protocol (PP) analysis. In all of the H. pylori-positive patients and separately in the CT and LT groups, the eradication rates were significantly lower in the filling group compared with the nonfilling group. However, in the QT group, there was no significant difference between the patients with and without fillings (P=0.001, 0.003, 0.012, 0.14, respectively). Logistic regression analysis showed that the absence of amalgam filling exerts independent effects on the increased frequency of H. pylori infection and increased rate of H. pylori eradication. CONCLUSION This is the first study to show a lower frequency of H. pylori colonization in patients with amalgam fillings than without and that H. pylori eradication rates are lower in patients with amalgam fillings compared to those without.
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Silva FM, de Queiroz ECS, Navarro-Rodriguez T, Barbuti RC, Mattar R, Iriya K, Lee JH, Eisig JN. Efficacy of levofloxacin, amoxicillin and a proton pump inhibitor in the eradication of Helicobacter pylori in Brazilian patients with peptic ulcers. Clinics (Sao Paulo) 2015; 70:318-21. [PMID: 26039946 PMCID: PMC4449484 DOI: 10.6061/clinics/2015(05)02] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 01/28/2015] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES The eradication of Helicobacter (H.) pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin) has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication. METHODS Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days. RESULTS A total of 66 patients were evaluated. The patients' mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74%) and were mild to moderate, with a prevalence of diarrhea complaints. CONCLUSIONS Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen.
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Affiliation(s)
- Fernando Marcuz Silva
- Division of Clinical Medicine and Propaedeutics, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
- *Corresponding author: Fernando Marcuz Silva, E-mail:
| | - Elaine Cristina Silveira de Queiroz
- Division of Clinical Medicine and Propaedeutics, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
| | - Tomás Navarro-Rodriguez
- Division of Gastroenterology and Clinical Hepatology (HCFMUSP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
| | - Ricardo Correa Barbuti
- Division of Gastroenterology and Clinical Hepatology (HCFMUSP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
| | - Rejane Mattar
- Division of Gastroenterology and Clinical Hepatology (HCFMUSP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
| | - Kiyoshi Iriya
- Division of Anatomic Pathology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
| | - Jin Hwa Lee
- Division of Anatomic Pathology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
| | - Jaime Natan Eisig
- Division of Gastroenterology and Clinical Hepatology (HCFMUSP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo/SP, Brazil
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Gisbert JP, Romano M, Gravina AG, Solís-Muñoz P, Bermejo F, Molina-Infante J, Castro-Fernández M, Ortuño J, Lucendo AJ, Herranz M, Modolell I, Del Castillo F, Gómez J, Barrio J, Velayos B, Gómez B, Domínguez JL, Miranda A, Martorano M, Algaba A, Pabón M, Angueira T, Fernández-Salazar L, Federico A, Marín AC, McNicholl AG. Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments. Aliment Pharmacol Ther 2015; 41:768-775. [PMID: 25703120 DOI: 10.1111/apt.13128] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2014] [Revised: 11/22/2014] [Accepted: 01/29/2015] [Indexed: 01/10/2023]
Abstract
BACKGROUND The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens. AIMS To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed. METHODS This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.), levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by (13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by questionnaires. RESULTS 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37). A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was serious. CONCLUSIONS Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed.
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Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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15
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Gisbert JP, Romano M, Molina-Infante J, Lucendo AJ, Medina E, Modolell I, Rodríguez-Tellez M, Gomez B, Barrio J, Perona M, Ortuño J, Ariño I, Domínguez-Muñoz JE, Perez-Aisa Á, Bermejo F, Domínguez JL, Almela P, Gomez-Camarero J, Millastre J, Martin-Noguerol E, Gravina AG, Martorano M, Miranda A, Federico A, Fernandez-Bermejo M, Angueira T, Ferrer-Barcelo L, Fernández N, Marín AC, McNicholl AG. Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments. Dig Liver Dis 2015; 47:108-113. [PMID: 25454706 DOI: 10.1016/j.dld.2014.10.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Revised: 09/01/2014] [Accepted: 10/12/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. METHODS Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400mg qd), amoxicillin (1g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by (13)C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. RESULTS 250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). CONCLUSION 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen.
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Affiliation(s)
- Javier P Gisbert
- Univeristy Hospital La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Spain.
| | - Marco Romano
- University Hospital, Seconda University of Naples, Naples, Italy
| | | | | | | | | | | | - Blas Gomez
- Hospital Quirón Sagrado Corazón, Seville, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Agnese Miranda
- University Hospital, Seconda University of Naples, Naples, Italy
| | | | | | | | | | | | - Alicia C Marín
- Univeristy Hospital La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Spain
| | - Adrián G McNicholl
- Univeristy Hospital La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Spain
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Ierardi E, Losurdo G, Giorgio F, Iannone A, Principi M, Leo AD. Quinolone-based first, second and third-line therapies for Helicobacter pylori. World J Pharmacol 2015; 4:274. [DOI: 10.5497/wjp.v4.i4.274] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 10/08/2015] [Accepted: 11/17/2015] [Indexed: 02/07/2023] Open
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Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: Past, present and future. World J Gastrointest Pathophysiol 2014; 5:392-399. [PMID: 25400982 PMCID: PMC4231503 DOI: 10.4291/wjgp.v5.i4.392] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 04/15/2014] [Accepted: 07/17/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.
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Heo J, Jeon SW, Jung JT, Kwon JG, Kim EY, Lee DW, Seo HE, Ha CY, Kim HJ, Kim ES, Park KS, Cho KB, Lee SH, Jang BI. A randomised clinical trial of 10-day concomitant therapy and standard triple therapy for Helicobacter pylori eradication. Dig Liver Dis 2014; 46:980-4. [PMID: 25132282 DOI: 10.1016/j.dld.2014.07.018] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 07/07/2014] [Accepted: 07/20/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND As a result of increased resistance to antibiotics, Helicobacter pylori eradication rates using standard triple therapy have been declining. AIM To validate the efficacy and tolerability of a concomitant regimen as a first-line treatment for H. pylori infection. METHODS A total of 348 naïve H. pylori-infected patients from six hospitals in Korea were randomly assigned to concomitant therapy and standard triple therapy groups. The concomitant regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for 10 days. The standard triple regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, and 500 mg of clarithromycin, twice daily for 10 days. RESULTS Concomitant and standard eradication rates were 78.7% (137/174) vs. 70.7% (123/174) by intention-to-treat (p=0.084) and 88.7% (133/150) vs. 78.4% (120/153) by per-protocol (p=0.016), respectively. The two groups were similar with regard to the incidence of adverse events. CONCLUSIONS Although 10-day concomitant therapy was validated as a suboptimal treatment option for the treatment of H. pylori infection, this regimen is expected to be a promising starting point in the development of an optimal treatment regimen for H. pylori infection.
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Affiliation(s)
- Jun Heo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Seong Woo Jeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.
| | - Jin Tae Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Joong Goo Kwon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Eun Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Dong Wook Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea
| | - Hyang Eun Seo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea
| | - Chang Yoon Ha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Hyun Jin Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Kyung Sik Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Kwang Bum Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Si Hyung Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
| | - Byung Ik Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
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Current Paradigm and Future Directions for Treatment of Helicobacter pylori Infection. ACTA ACUST UNITED AC 2014; 12:373-84. [PMID: 25187235 DOI: 10.1007/s11938-014-0027-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OPINION STATEMENT Once easily eradicated with triple or quadruple therapy, Helicobacter pylori infection has become increasingly resistant to traditional first-line treatment regimens because of emerging antibiotic resistance coupled with poor patient compliance with completing the treatment course. Given decreasing H. pylori eradication rates, there is considerable interest in evaluating new antibiotic combinations and regimens, the addition of probiotics, and the development of new paradigms such as concomitant, sequential, and hybrid medication dosing strategies. Unfortunately, efforts thus far have not universally improved treatment responses, as promising early results were often not extrapolated to wider populations. This is probably due largely to regional variation in H. pylori resistance patterns. Ideally, the standard of care should be dictated by knowledge of local H. pylori antimicrobial resistance patterns and clinical success rates rather than by empiric extrapolation from the literature. Unfortunately, such knowledge is usually lacking in the USA. The expectation of a first-line regimen is a minimum 80 % eradication rate in the local population. Standard triple therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin may still be effective in some areas; however, in populations with high clarithromycin resistance, quadruple therapy with a metronidazole-based regimen may be a better choice, and concomitant, sequential, or hybrid dosing schedules should also be considered as possible first-line choices. Second- and third-line treatment regimens consist of levofloxacin-based and rifabutin-based therapies, respectively. Further work should be directed at establishing local resistance patterns and eradication rates, developing H. pylori-specific antibiotics, and starting culture-guided treatment programs. Ultimately, the development of an H. pylori vaccine would bypass any issues with antibiotic resistance by preventing the acquisition of infection altogether.
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Abstract
This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, predominantly optimized triple therapies and non-bismuth quadruple schemes. Regarding newer non-bismuth quadruple regimens, the compliance and tolerance seem to be similar for sequential and concomitant regimens. Notably, no study yet has demonstrated a clear statistical superiority for either, and a systematic review and meta-analysis may be warranted. Other studies examined the role of levofloxacin and bismuth based therapies in H. pylori eradication. The efficacy of bismuth as a second-line after sequential therapy was particularly noteworthy. Levofloxacin-based therapies also appear to be useful and versatile as part of different antibiotic combinations and in first-, second-, and third-line therapies. The emerging problem of quinolone resistance remains a worry. Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.
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Affiliation(s)
- Anthony O'Connor
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
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Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance. World J Gastroenterol 2014; 20:9898-911. [PMID: 25110420 PMCID: PMC4123371 DOI: 10.3748/wjg.v20.i29.9898] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 01/27/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.
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Rispo A, Capone P, Castiglione F, Pasquale L, Rea M, Caporaso N. Fluoroquinolone-based protocols for eradication of Helicobacter pylori. World J Gastroenterol 2014; 20:8947-8956. [PMID: 25083067 PMCID: PMC4112890 DOI: 10.3748/wjg.v20.i27.8947] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori.
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Oh DH, Lee DH, Kang KK, Park YS, Shin CM, Kim N, Yoon H, Hwang JH, Jeoung SH, Kim JW, Jang ES, Jung HC. Efficacy of hybrid therapy as first-line regimen for Helicobacter pylori infection compared with sequential therapy. J Gastroenterol Hepatol 2014; 29:1171-6. [PMID: 24955448 DOI: 10.1111/jgh.12518] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Recent prospective studies have shown that the sequential therapy has not achieved the target Helicobacter pylori eradication rate of > 80% in Korea. The aim of this study was to therefore assess the efficacy of the hybrid therapy as a first-line treatment for H. pylori eradication in a prospective trial. METHODS From December 2012 to August 2013, 184 patients with confirmed H. pylori infections received either the 14-day hybrid therapy or the 14-day sequential therapy. Eradication outcomes were evaluated using a 13C-urea breath test at least 4 weeks after treatment cessation. RESULTS A total of 184 patients (90 receiving hybrid treatment and 94 receiving sequential treatment) completed the study. The eradication rates of the hybrid and sequential therapy groups were 81.1% (73/90; 95% confidence interval [CI] = 73.0-89.2%) and 79.8% (75/94; 95%CI = 71.7-87.9%), respectively, by intention-to-treat analysis (P = 0.821). By per protocol analysis, eradication rates were 85.9% (73/85; 95%CI = 78.5-93.3%) and 82.0% (73/89; 95%CI = 74.0-89.9%; P = 0.489), respectively. There were no significant intergroup differences in treatment compliance or discontinuation induced by severe side effects. CONCLUSIONS The hybrid therapy achieved acceptable eradication rate (85.9%), but not statistically significantly higher rates than the sequential therapy (82.0%). Further studies are therefore needed to identify first-line treatments with even better eradication rates in the Korean population.
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Heo J, Jeon SW. Optimal treatment strategy for Helicobacter pylori: Era of antibiotic resistance. World J Gastroenterol 2014; 20:5654-5659. [PMID: 24914324 PMCID: PMC4024773 DOI: 10.3748/wjg.v20.i19.5654] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/29/2013] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
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.
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Alahdab YO, Kalayci C. Helicobacter pylori: Management in 2013. World J Gastroenterol 2014; 20:5302-5307. [PMID: 24833860 PMCID: PMC4017045 DOI: 10.3748/wjg.v20.i18.5302] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 11/15/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a prevalent, worldwide, chronic infection. Choice of treatment can be modified according to antibiotic-resistance rates of H. pylori. The ideal therapeutic regimen for H. pylori infection should achieve an eradication rate of ≥ 80%. In some countries, triple therapy with a proton-pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole is still the best option. Bismuth-containing quadruple therapy consisting of bismuth salts, tetracycline, metronidazole and PPI, may be the preferred option in countries with clarithromycin resistance > 20%. Sequential therapy including a PPI and amoxicillin given for the first 5 d, followed by triple therapy including a PPI, clarithromycin, and nitroimidazole antimicrobial (all twice daily) for the remaining 5 d, can be another option for the first-line treatment of H. pylori. Recent data suggest that treatment with PPI, levofloxacin, and amoxicillin for 10 d is a good choice for second-line therapy. Concomitant therapy consisting of PPI, amoxicillin, clarithromycin and metronidazole is another option for second-line treatment. If second-line treatment also fails, it is recommended to culture H. pylori from biopsy specimens and perform antimicrobial susceptibility testing. Rescue treatment should be based on antimicrobial susceptibility.
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Song M, Ang TL. Second and third line treatment options for Helicobacter pylori eradication. World J Gastroenterol 2014; 20:1517-1528. [PMID: 24587627 PMCID: PMC3925860 DOI: 10.3748/wjg.v20.i6.1517] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 10/29/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and third-line treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.
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Kanizaj TF, Kunac N. Helicobacter pylori: Future perspectives in therapy reflecting three decades of experience. World J Gastroenterol 2014; 20:699-705. [PMID: 24574743 PMCID: PMC3921479 DOI: 10.3748/wjg.v20.i3.699] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/05/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori (H. pylori) eradication protocols, and to develop new ones. Various bacterial and host factors are evaluated, and their contribution to eradication failure is estimated. For a long time being considered the cornerstone eradication scheme, the standard triple therapy has been replaced with novel, more efficient regimens, namely sequential and concomitant, along with the emergence of a new design of bismuth quadruple therapy. A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant (clarithromycin and metronidazole) H. pylori. Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy, making eradication success close to originally desirable rates. Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes, so various probiotic compound supplements are taken into consideration. Finally, we summarize the emerging efforts and obstacles in creating efficient H. pylori vaccine.
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Enfermedades relacionadas con la infección por Helicobacter pylori. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 36 Suppl 2:39-50. [DOI: 10.1016/s0210-5705(13)70052-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Gisbert JP, Calvet X, Ferrándiz J, Mascort J, Alonso-Coello P, Marzo M. [Clinical practice guideline on the management of patients with dyspepsia. Update 2012]. Aten Primaria 2012; 44:727.e1-727.e38. [PMID: 23036729 PMCID: PMC7025630 DOI: 10.1016/j.aprim.2012.05.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Accepted: 05/30/2012] [Indexed: 12/13/2022] Open
Abstract
The aim of the Clinical Practice Guideline (CPG) on the Management of Patients with Dyspepsia is to generate recommendations on the optimal approach to dyspepsia in the primary care and specialized outpatient setting. The main objective of this CPG is to help to optimize the diagnostic process, identifying patients with a low risk of a serious organic disease (mainly tumoral), who could be safely managed without the need for invasive diagnostic tests and/or referral to a specialist. The importance of this aim lies in the need to accurately diagnose patients with esophagogastric cancer and correctly treat peptic ulcer while, at the same time, reduce negative endoscopies in order to appropriately use the available healthcare resources. This CPG reviews the initial strategies that can be used in patients with uninvestigated dyspepsia and evaluates the possible decision to begin empirical therapy or to investigate the existence of a lesion that could explain the symptoms. This CPG also discusses functional dyspepsia, which encompasses all patients with dyspepsia with no demonstrable cause on endoscopy. Recommendations for the diagnosis and treatment of peptic ulcer and Helicobacter pylori infection are also made. To classify the scientific evidence and strengthen the recommendations, the GRADE (Grading of Recommendations Assessment, Development and Evaluation Working Group) system has been used (http://www.gradeworkinggroup.org/).
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Affiliation(s)
- Javier P. Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, España
| | - Xavier Calvet
- Corporació Universitària Parc Taulí, Departament de Medicina, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, España
| | - Juan Ferrándiz
- Subdireccion de Calidad, Dirección General de Atención al Paciente, Servicio Madrileño de Salud, Madrid, España
| | - Juan Mascort
- CAP Florida Sud, Institut Català de la Salut, Departament de Ciències Clíniques, Campus Bellvitge, Facultat de Medicina, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, España
| | - Pablo Alonso-Coello
- Centro Cochrane Iberoamericano, Instituto de Investigaciones Biomédicas (IIB Sant Pau) Barcelona, España
| | - Mercè Marzo
- Unitat de suport a la recerca – IDIAP Jordi Gol, Direcció d’Atenció Primària Costa De Ponent, Institut Català de la Salut, Barcelona, España
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