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1
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Chen X, Guo Y, Shi J, Wang Y, Guo X, Wu G, Li S, Zhang T. Structural basis for substrate and antibiotic recognition by Helicobacter pylori isoleucyl-tRNA synthetase. FEBS Lett 2024; 598:521-536. [PMID: 38246751 DOI: 10.1002/1873-3468.14805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 12/12/2023] [Accepted: 12/21/2023] [Indexed: 01/23/2024]
Abstract
Helicobacter pylori infection is a global health concern, affecting over half of the world's population. Acquiring structural information on pharmacological targets is crucial to facilitate inhibitor design. Here, we have determined the crystal structures of H. pylori isoleucyl-tRNA synthetase (HpIleRS) in apo form as well as in complex with various substrates (Ile, Ile-AMP, Val, and Val-AMP) or an inhibitor (mupirocin). Our results provide valuable insights into substrate specificity, recognition, and the mechanism by which HpIleRS is inhibited by an antibiotic. Moreover, we identified Asp641 as a prospective regulatory site and conducted biochemical analyses to investigate its regulatory mechanism. The detailed structural information acquired from this research holds promise for the development of highly selective and effective inhibitors against H. pylori infection.
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Affiliation(s)
- Xiaobao Chen
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 500 Yonghe Road, Nantong, China
| | - Yu Guo
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, China
- Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, China
- School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Jiawen Shi
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 500 Yonghe Road, Nantong, China
| | - Yilun Wang
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 500 Yonghe Road, Nantong, China
| | - Xinyi Guo
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 500 Yonghe Road, Nantong, China
| | - Guihua Wu
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 500 Yonghe Road, Nantong, China
| | - Sheng Li
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, China
- Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, China
| | - Tianlong Zhang
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 500 Yonghe Road, Nantong, China
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Lee JW. Fluoroquinolone and Rifabutin-Containing Therapy. HELICOBACTER PYLORI 2023:587-594. [DOI: 10.1007/978-981-97-0013-4_49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Choi YI, Lee SM, Chung JW, Kim KO, Kwon KA, Kim YJ, Kim JH, Lee SM, Jeong JY, Park DK. Therapeutic Potential of Sitafloxacin as a New Drug Candidate for Helicobacter Eradication in Korea: An In Vitro Culture-Based Study. Antibiotics (Basel) 2021; 10:antibiotics10101242. [PMID: 34680822 PMCID: PMC8532961 DOI: 10.3390/antibiotics10101242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/22/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022] Open
Abstract
Background: Increased prevalence of antibiotic resistance to Helicobacter pylori (H. pylori) infection worldwide has driven the search for a new therapeutic candidate. Recently, sitafloxacin, a novel 4-quinolone agent, has emerged as a new therapeutic option for H. pylori eradication, in Japan. However, data on its efficacy for H. pylori eradication in Korea are limited. Therefore, we aimed to investigate the therapeutic potential of sitafloxacin as a first-line treatment for patients with Helicobacter infection through gastric tissue culture-based studies. Materials and Methods: We prospectively enrolled treatment-naïve patients with H. pylori infection who visited the Gil Medical Center between March 2015 and March 2018. After obtaining written informed consent from patients, a total of 121 H. pylori strains were collected. We tested the susceptibility of these strains to sitafloxacin, and other antibiotics for Helicobacter eradication, including clarithromycin (CLR), metronidazole (MTZ), amoxicillin (AMX), tetracycline (TET), levofloxacin (LEV), and ciprofloxacin (CIP) using the agar dilution technique. The minimum inhibitory concentration (MIC) of these antibiotics against H. pylori strains were determined. Results: None of the H. pylori strains obtained were resistant to sitafloxacin (MIC > 1, n = 0), while other conventional eradication drugs including CLR, MTZ, AMX, and TET showed 24.8% (n = 30), 30.6% (n = 37), 5.0% (n = 6), and 0.8% (n = 1) resistance, respectively. Compared to the resistance rates of other quinolones (LEV [36.4%, n = 44] and CIP [37.2%, n = 45]), sitafloxacin showed the best antibiotic performance against Helicobacter strains (0%, n = 0). Furthermore, sitafloxacin also inhibited the growth of 14 H. pylori strains (12.4%), which were resistant to both of clarithromycin, and metronidazole, and 27 strains (22.3%) with multidrug resistance. Conclusions: Sitafloxacin might be a new promising candidate for Helicobacter eradication where antibiotic resistance for Helicobacter is an emerging medical burden, such as in Korea.
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Affiliation(s)
- Youn I Choi
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
| | - Sung Min Lee
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
| | - Jun-Won Chung
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
- Correspondence: ; Tel.: +82-32-460-3778
| | - Kyoung Oh Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
| | - Kwang An Kwon
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
| | - Yoon Jae Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
| | - Jung Ho Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
| | - Sun Mi Lee
- Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.M.L.); (J.-Y.J.)
| | - Jin-Yong Jeong
- Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.M.L.); (J.-Y.J.)
| | - Dong Kyun Park
- Department of Gastroenterology, Gil Medical Center, Gachon University, Incheon 21565, Korea; (Y.I.C.); (S.M.L.); (K.O.K.); (K.A.K.); (Y.J.K.); (J.H.K.); (D.K.P.)
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Gisbert JP. Optimization Strategies Aimed to Increase the Efficacy of Helicobacter pylori Eradication Therapies with Quinolones. Molecules 2020; 25:E5084. [PMID: 33147814 PMCID: PMC7663000 DOI: 10.3390/molecules25215084] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 10/28/2020] [Accepted: 10/31/2020] [Indexed: 12/14/2022] Open
Abstract
H. pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. Fluoroquinolones such as levofloxacin, or more recently moxifloxacin or sitafloxacin, are efficacious alternatives to standard antibiotics for H. pylori eradication. The aim of the present review is to summarize the role of quinolone-based eradication therapies, mainly focusing on the optimization strategies aimed to increase their efficacy. Several meta-analyses have shown that, after failure of a first-line eradication treatment, a levofloxacin-containing rescue regimen is at least equally effective, and better tolerated, than the generally recommended bismuth quadruple regimen. Compliance with the levofloxacin regimens is excellent, and the safety profile is favourable. Higher cure rates have been reported with longer treatments (>10-14 days), and 500 mg levofloxacin daily is the recommended dose. Adding bismuth to the standard triple regimen (PPI-amoxicillin-levofloxacin) has been associated with encouraging results. Unfortunately, resistance to quinolones is easily acquired and is increasing in most countries, being associated with a decrease in the eradication rate of H. pylori. In summary, a quinolone (mainly levofloxacin)-containing regimen is an encouraging second-line (or even third-line) strategy, and a safe and simple alternative to bismuth quadruple therapy in patients whose previous H. pylori eradication therapy has failed.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
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Mori H, Suzuki H. Update on quinolone-containing rescue therapies for Helicobacter pylori infection. World J Gastroenterol 2020; 26:1733-1744. [PMID: 32351290 PMCID: PMC7183861 DOI: 10.3748/wjg.v26.i15.1733] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/05/2020] [Accepted: 04/04/2020] [Indexed: 02/06/2023] Open
Abstract
Third generation of quinolones, such as levofloxacin and moxifloxacin, -containing regimens are often used in second-line or rescue treatment of Helicobacter pylori infection. However, the increasing antibiotic resistance to quinolones affects the efficacies of quinolones-containing therapies in recent years. Therefore, there is a need to enhance the effectiveness of quinolones-containing therapies. Sitafloxacin, a fourth-generation quinolone, and vonoprazan, a novel potassium-competitive acid blocker, are now available as more effective treatment options. The aim of this paper is to summarize the current evidence of quinolone-containing therapies in rescue treatments, and to discuss the importance of drug sensitivity tests or analysis of gyrA mutation before treatments.
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Affiliation(s)
- Hideki Mori
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven 3000, Belgium
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan
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6
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Effect of residue substitution via site-directed mutagenesis on activity and steroselectivity of transaminase BpTA from Bacillus pumilus W3 for sitafloxacin hydrate intermediate. Int J Biol Macromol 2019; 137:732-740. [DOI: 10.1016/j.ijbiomac.2019.07.027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 05/24/2019] [Accepted: 07/03/2019] [Indexed: 11/22/2022]
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Blaecher C, Bauwens E, Tay A, Peters F, Dobbs S, Dobbs J, Charlett A, Ducatelle R, Haesebrouck F, Smet A. A novel isolation protocol and probe-based RT-PCR for diagnosis of gastric infections with the zoonotic pathogen Helicobacter suis. Helicobacter 2017; 22. [PMID: 28029188 DOI: 10.1111/hel.12369] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Helicobacter suis is a very fastidious microorganism associated with gastritis, gastric ulcers, and mucosa-associated lymphoid tissue lymphoma in humans. In vitro isolation of this agent from human patients has so far been unsuccessful. MATERIALS AND METHODS A probe-based real-time PCR (RT-PCR) for the rapid detection of H. suis in gastric biopsies was developed. Secondly, a mouse-passage-based protocol was optimized for isolation of low numbers of viable H. suis bacteria. Mice were inoculated with different numbers of viable H. suis (102 -108 ) and kept for 4 weeks to allow multiplication of this pathogen. RESULTS The probe-based real-time PCR (RT-PCR) exhibited a high degree of diagnostic specificity and analytical sensitivity, high linear correlations (r2 between 0.995 and 0.999), and high amplification efficiencies (>90%) for H. suis. No cross-reactivity was detected with human, porcine, non-human primate, and murine DNA nor with DNA from other bacteria including Helicobacter spp. and Campylobacter spp. H. suis was successfully re-isolated from the stomach of mice inoculated with at least 104 viable H. suis, using a biphasic medium (pH 5), consisting of Brucella agar with Brucella broth on top, both supplemented with vitox supplement, Campylobacter-selective supplement, amphotericin (5 μg/mL), HCl (0.05%), fetal bovine serum (20%), and linezolid (5 μg/mL). Linezolid was necessary to inhibit proliferation of contaminants, including lactobacilli. CONCLUSION The methods described above can be implemented for detection or isolation of H. suis from human gastric biopsies.
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Affiliation(s)
- Caroline Blaecher
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Eva Bauwens
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Alfred Tay
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, WA, Australia
| | - Fanny Peters
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, WA, Australia
| | - Sylvia Dobbs
- Institute of Pharmaceutical Science, King's College London, London, UK.,The Maudsley Hospital, London, UK.,Department of Gastroenterology, King's College Hospital, London, UK
| | - John Dobbs
- Institute of Pharmaceutical Science, King's College London, London, UK.,The Maudsley Hospital, London, UK.,Department of Gastroenterology, King's College Hospital, London, UK
| | - André Charlett
- Institute of Pharmaceutical Science, King's College London, London, UK.,Statistics Unit, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK
| | - Richard Ducatelle
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Freddy Haesebrouck
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Annemieke Smet
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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Lim JH, Kim SG, Song JH, Hwang JJ, Lee DH, Han JP, Hong SJ, Kim JH, Jeon SW, Kim GH, Shim KN, Shin WG, Kim TH, Kim SM, Chung IK, Kim HS, Kim HU, Lee J, Kim JG. Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of Helicobacter pylori in Peptic Ulcer Disease. Gut Liver 2017; 11:226-231. [PMID: 27609487 PMCID: PMC5347646 DOI: 10.5009/gnl16099] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 03/25/2016] [Accepted: 03/25/2016] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND/AIMS The resistance rate of Helicobacter pylori is gradually increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line H. pylori eradication in peptic ulcer disease. METHODS Between 2002 and 2014, 110 patients in 14 medical centers received levofloxacin-based third-line H. pylori eradication therapy for peptic ulcer disease. Of these, 88 were included in the study; 21 were excluded because of lack of follow-up and one was excluded for poor compliance. Their eradication rates, treatment regimens and durations, and types of peptic ulcers were analyzed. RESULTS The overall eradiation rate was 71.6%. The adherence rate was 80.0%. All except one received a proton-pump inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor, amoxicillin, levofloxacin, and clarithromycin, and the eradication was successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days, and 32 for 14 days. No significant differences were observed in the eradication rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days, 68.8%, p=0.353). Additionally, no differences were found in the eradiation rates according to the type of peptic ulcer (gastric ulcer, 73.2% vs duodenal/gastroduodenal ulcer, 68.8%, p=0.655). CONCLUSIONS Levofloxacin-based third-line H. pylori eradication showed efficacy similar to that of previously reported first/second-line therapies.
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Affiliation(s)
- Joo Hyun Lim
- Department of Internal Medicine, Seoul National University Hospital, Healthcare System Gangnam Center, Healthcare Research Institute, Seoul,
Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul,
Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul,
Korea
| | - Ji Hyun Song
- Department of Internal Medicine, Seoul National University Hospital, Healthcare System Gangnam Center, Healthcare Research Institute, Seoul,
Korea
| | - Jae Jin Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam,
Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam,
Korea
| | - Jae Pil Han
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon,
Korea
| | - Su Jin Hong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon,
Korea
| | - Ji Hyun Kim
- Department of Internal Medicine, Inje University College of Medicine, Busan,
Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu,
Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan,
Korea
| | - Ki-Nam Shim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul,
Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Seoul,
Korea
| | - Tae Ho Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Bucheon,
Korea
| | - Sun Moon Kim
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon,
Korea
| | - Il-Kwon Chung
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju,
Korea
| | - Heung Up Kim
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju,
Korea
| | - Joongyub Lee
- Medical Research Collaborating Center, Seoul National University Hospital and Seoul National University College of Medicine, Seoul,
Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
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Shi J, Jiang Y, Zhao Y. Promising in vitro and in vivo inhibition of multidrug-resistant Helicobacter pylori by linezolid and novel oxazolidinone analogues. J Glob Antimicrob Resist 2016; 7:106-109. [DOI: 10.1016/j.jgar.2016.07.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 07/23/2016] [Indexed: 02/07/2023] Open
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Hirata Y, Serizawa T, Shichijo S, Suzuki N, Sakitani K, Hayakawa Y, Yamada A, Koike K. Efficacy of triple therapy with esomeprazole, amoxicillin, and sitafloxacin as a third-line Helicobacter pylori eradication regimen. Int J Infect Dis 2016; 51:66-69. [PMID: 27590563 DOI: 10.1016/j.ijid.2016.08.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 08/22/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To examine the efficacy of third-line Helicobacter pylori eradication therapy with esomeprazole, amoxicillin, and sitafloxacin for patients with clarithromycin- and metronidazole-based first- and second-line therapy failure. METHODS Thirty patients with first- and second-line H. pylori eradication failure were treated prospectively with esomeprazole 20mg twice daily, amoxicillin 750mg twice daily, and sitafloxacin 100mg twice daily for 7 days. After 8-12 weeks, the outcome of eradication therapy was assessed by 13C-urea breath test or stool antigen test. RESULTS All 30 patients completed the study. Eradication was successful in 25 patients and the eradication rate was 83% in the intention-to-treat and per-protocol analyses. No specific or significant adverse events were recorded in the 30 patients. Patient characteristics such as sex, body mass index, and pepsinogen I/II ratio did not differ between patients who were treated successfully and those who were not treated successfully. CONCLUSIONS Third-line H. pylori eradication therapy with esomeprazole, amoxicillin, and sitafloxacin is as safe and effective as previously reported sitafloxacin-based triple therapy.
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Affiliation(s)
- Yoshihiro Hirata
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Takako Serizawa
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Satoki Shichijo
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Nobumi Suzuki
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kosuke Sakitani
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yoku Hayakawa
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Atsuo Yamada
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Abstract
Helicobacter pylori is a ubiquitous gastropathogen infecting more than half of the world population. It is associated with dyspepsia, gastritis, gastroduodenal ulcers, mucus-associated lymphoid tissue lymphoma and gastric carcinoma. Current recommended therapy does not eradicate infection in all treated cases and at least 20% post-treatment patients continue to suffer. Salvage therapy helps some of these nonresponders, but resistance to available antibiotics is mounting. Hence, its treatment still remains a daunting task for the practicing physician. Novel medications with improved efficacy and tolerability and with less chances of resistance are required. The present review attempts to discuss the newer patents in this field, which demonstrate a promising future role in the management of H. pylori infection and its consequent problems.
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Boyanova L, Evstatiev I, Gergova G, Yaneva P, Mitov I. Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance. Int J Antimicrob Agents 2015; 46:703-6. [PMID: 26453146 DOI: 10.1016/j.ijantimicag.2015.08.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2015] [Revised: 08/12/2015] [Accepted: 08/13/2015] [Indexed: 10/23/2022]
Abstract
Only a few studies have evaluated Helicobacter pylori susceptibility to linezolid. The aim of the present study was to assess linezolid susceptibility in H. pylori, including strains with double/multidrug resistance. The susceptibility of 53 H. pylori strains was evaluated by Etest and a breakpoint susceptibility testing method. Helicobacter pylori resistance rates were as follows: amoxicillin, 1.9%; metronidazole, 37.7%; clarithromycin, 17.0%; tetracycline, 1.9%; levofloxacin, 24.5%; and linezolid (>4 mg/L), 39.6%. The linezolid MIC50 value was 31.2-fold higher than that of clarithromycin and 10.5-fold higher than that of levofloxacin; however, 4 of 11 strains with double/multidrug resistance were linezolid-susceptible. The MIC range of the oxazolidinone agent was larger (0.125-64 mg/L) compared with those in the previous two reports. The linezolid resistance rate was 2.2-fold higher in metronidazole-resistant strains and in strains resistant to at least one antibiotic compared with the remaining strains. Briefly, linezolid was less active against H. pylori compared with clarithromycin and levofloxacin, and linezolid resistance was linked to resistance to metronidazole as well as to resistance to at least one antibiotic. However, linezolid activity against some strains with double/multidrug resistance may render the agent appropriate to treat some associated H. pylori infections following in vitro susceptibility testing of the strains. Clinical trials are required to confirm this suggestion.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Microbiology, Medical University of Sofia, Zdrave Street 2, Sofia 1431, Bulgaria.
| | - Ivailo Evstatiev
- Department of Gastroenterology, University Hospital St Ekaterina, Medical University of Sofia, blvd. Pencho Slaveikov 52A, Sofia, Bulgaria
| | - Galina Gergova
- Department of Microbiology, Medical University of Sofia, Zdrave Street 2, Sofia 1431, Bulgaria
| | - Penka Yaneva
- Gastroenterology Clinic, Department of Pediatrics, University Pediatric Hospital, blvd. Acad. Iv. Geshov 11, Sofia, Bulgaria
| | - Ivan Mitov
- Department of Microbiology, Medical University of Sofia, Zdrave Street 2, Sofia 1431, Bulgaria
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Sugimoto M, Sahara S, Ichikawa H, Kagami T, Uotani T, Furuta T. High Helicobacter pylori cure rate with sitafloxacin-based triple therapy. Aliment Pharmacol Ther 2015; 42:477-483. [PMID: 26075959 DOI: 10.1111/apt.13280] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 03/09/2015] [Accepted: 05/27/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Bacterial resistance of Helicobacter pylori to antibiotics is increasing and it often leads to failure of antibiotic treatment. A new sitafloxacin-based triple therapy was developed to counter this situation; the fluoroquinolone sitafloxacin has a low minimum inhibitory concentration for H. pylori. AIM To investigate the efficacy in Japanese patients of sitafloxacin-based triple therapy and document its efficacy in relation to anti-microbial susceptibility. METHODS We investigated the efficacy of a 1-week sitafloxicin-based regimen of rabeprazole 10 mg four times daily (q.d.s.), metronidazole 250 mg twice daily (b.d.) and sitafloxacin 100 mg b.d. in 180 H. pylori-positive Japanese patients (first-line treatment: n = 45, second-line; n = 41, third-line: n = 94). At 8 weeks, patients were given the (13) C-urea breath test to assess eradication status. RESULTS Eradication rate was 92.2% [95% confidence interval (CI): 87.3-95.7%, 166/180] in intention-to-treat analysis. Although the eradication rate was higher in patients treated with first-line therapy [45/45 (100%, 95% CI: 83.4-100%)] than in those with second- [38/41 (92.7%, 80.1-98.5%)] or third-line therapy [83/94 (88.3%, 80.0-94.0%)], no significant differences were noted with respect to the number of previous therapy attempts (P = 0.054). Eradication rates in patients infected with sensitive- and resistant strains to metronidazole were 96.6% (28/29) and 96.3% (77/80) (P = 0.941), respectively, while rates were 98.4% (60/61) in sitafloxacin-sensitive and 50.0% (1/2) in sitafloxacin resistant strains (P < 0.001). CONCLUSION Sitofloxacin-based triple therapy with metronidazole b.d. and rabeprazole q.d.s. achieved an eradication rate exceeding 88%, irrespective of eradication history, CYP2C19 genotype, or metronidazole resistance status.
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Affiliation(s)
- M Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga, Japan
| | - S Sahara
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - H Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - T Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - T Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - T Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan
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Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy. Dig Dis Sci 2015; 60:458-64. [PMID: 25236423 DOI: 10.1007/s10620-014-3365-2] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Accepted: 09/09/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori eradication is a challenge in penicillin allergy. AIM To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. METHODS Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. RESULTS In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p < 0.05). Compliance with treatment was 94 and 98 %, respectively. Adverse events were reported in 14 % with both regimens (all mild). (2) Second-line treatment: Intention-to-treat eradication rate with omeprazole-clarithromycin-levofloxacin was 64 % both after triple and quadruple failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. CONCLUSION In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.
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Kim JH. Recent Update on Third-lineHelicobacter pyloriEradication. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2015. [DOI: 10.7704/kjhugr.2015.15.2.89] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Ji Hyun Kim
- Department of Gastroenterology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
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Tai WC, Lee CH, Chiou SS, Kuo CM, Kuo CH, Liang CM, Lu LS, Chiu CH, Wu KL, Chiu YC, Hu TH, Chuah SK. The clinical and bacteriological factors for optimal levofloxacin-containing triple therapy in second-line Helicobacter pylori eradication. PLoS One 2014; 9:e105822. [PMID: 25141137 PMCID: PMC4139398 DOI: 10.1371/journal.pone.0105822] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 07/24/2014] [Indexed: 01/10/2023] Open
Abstract
Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9–85.3%) and 90.5% (95% CI = 84.5–98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6–78.5%) and 84.8% (95% CI = 76.8–93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful treatment. This study suggests that tailored levofloxacin-containing therapy should be administered only for patients with susceptible strains because it can achieve >90% success rates.
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Affiliation(s)
- Wei-Chen Tai
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chen-Hsiang Lee
- Division of Infectious Diseases, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shue-Shian Chiou
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Mou Kuo
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Huang Kuo
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Ming Liang
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Lung-Sheng Lu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hua Chiu
- Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Keng-Liang Wu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Chun Chiu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Seng-Kee Chuah
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
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Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Uotani T, Sahara S, Ichikawa H, Yamada T, Osawa S, Sugimoto K, Watanabe H, Umemura K. Sitafloxacin-based third-line rescue regimens for Helicobacter pylori infection in Japan. J Gastroenterol Hepatol 2014; 29:487-493. [PMID: 24224808 DOI: 10.1111/jgh.12442] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUNDS Quinolone-based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin-based eradication regimens as rescue for the eradication of H. pylori. METHODS We attempted to eradicate H. pylori in 180 Japanese patients who had never failed in eradication of H. pylori with the triple proton pump inhibitor/amoxicillin/clarithromycin therapy (1st line) and the triple proton pump inhibitor/amoxicillin/metronidazole therapy (2nd line). They were assigned to either the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., amoxicillin 500 mg q.i.d, and sitafloxacin 100 mg b.i.d. (RAS) for 1 or 2 weeks or the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., metronidazole 250 mg b.i.d., and sitafloxacin 100 mg b.i.d. (RMS) for 1 or 2 weeks. Eradication was assessed via the (13) C-urea breath test and rapid urease test. RESULTS Intention-to-treat and per-protocol analyses of eradication rates were 84.1% (37/44) and 86.4% (37/43) with RAS for 1 week, 88.9% (40/45) and 90.9% (40/44) for RAS for 2 weeks, 90.9% (40/44) and 90.9% (40/44) for 1 week-RMS and 87.2% (41/47) and 91.1% (41/45) with RMS for 2 weeks. We noted no statistical significant differences in eradication rates among four regimens. CONCLUSION All of the above-described rescue regimens proved relatively equally useful in the eradication of H. pylori. Of them, RAS for 2 weeks and RMS for 1 or 2 weeks could attain the rescue eradication rates higher than 90% by per-protocol analysis.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Murakami K, Furuta T, Ando T, Nakajima T, Inui Y, Oshima T, Tomita T, Mabe K, Sasaki M, Suganuma T, Nomura H, Satoh K, Hori S, Inoue S, Tomokane T, Kudo M, Inaba T, Take S, Ohkusa T, Yamamoto S, Mizuno S, Kamoshida T, Amagai K, Iwamoto J, Miwa J, Kodama M, Okimoto T, Kato M, Asaka M. Multi-center randomized controlled study to establish the standard third-line regimen for Helicobacter pylori eradication in Japan. J Gastroenterol 2013; 48:1128-35. [PMID: 23307042 DOI: 10.1007/s00535-012-0731-8] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2012] [Accepted: 12/04/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUNDS The present study sought to establish a standard third-line eradication regimen for Helicobacter pylori in Japan. METHODS Subjects were 204 patients with H. pylori infection in whom the standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX. RESULTS Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %; p < 0.05) and the LAL group (43.1 %; p < 0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX. CONCLUSIONS The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for H. pylori in Japan.
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Affiliation(s)
- Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yuhu, Oita, 879-5593, Japan,
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Calhan T, Kahraman R, Sahin A, Senates E, Doganay HL, Kanat E, Ozdil K, Sokmen HM. Efficacy of two levofloxacin-containing second-line therapies for Helicobacter pylori: a pilot study. Helicobacter 2013; 18:378-383. [PMID: 23601026 DOI: 10.1111/hel.12056] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND An ideal second-line therapeutic regimen for the treatment of patients who do not respond to standard triple therapy is currently being investigated. In this study, we aimed to investigate the efficacy of two levofloxacin-containing second-line therapies for Helicobacter pylori (H. pylori). MATERIALS AND METHODS One hundred and forty eight consecutive H. pylori -positive patients who did not respond to the standard triple therapy (77 female, 71 male) were enrolled in the study. The patients were randomized consecutively to two-second-line therapy groups; 73 to the levofloxacin-containing sequential (LCS) and 75 to the levofloxacin-containing quadruple (LCQ) therapy group. The LCS therapy group received pantoprazole 40 mg and amoxicillin 1,000 mg twice daily for 5 days followed by pantoprazole 40 mg twice daily and metronidazole 500 mg three times daily and levofloxacin 500 mg one time daily for 7 days. The LCQ therapy group received pantoprazole 40 mg twice daily, tetracycline 500 mg four times daily, bismuth subcitrate 300 mg four times daily and levofloxacin 500 mg one time daily for 10 days. H. pylori eradication was confirmed by stool antigen testing at least 6 weeks after cessation of therapy. Side-effects and compliance were assessed by a questionnaire. RESULTS Intention-to-treat cure rates were: 82.2% (95%CI; 73-91) and 90.6% (95%CI; 79-95) in the LCS and LCQ therapy, respectively. Per protocol cure rates were: 85.7% (95%CI; 75-92) and 93.1% (95%CI; 85-98) in the LCS and LCQ therapy, respectively. No statistically significant difference was found between two groups (p = .1). No differences in compliance or adverse effects were demonstrated between two groups. CONCLUSIONS This prospective trial demonstrates that both levofloxacin-containing sequential therapy and levofloxacin-containing quadruple therapy regimens have higher H. pylori eradication rates and are well tolerated. The levofloxacin-containing quadruple therapy is likely the best treatment option for a second-line therapy, at least in the Turkish population.
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Affiliation(s)
- Turan Calhan
- Department of Gastroenterology, Umraniye Training and Research Hospital, Istanbul, Turkey
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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; 48:652-6. [PMID: 23556551 DOI: 10.3109/00365521.2013.786132] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Non-bismuth quadruple "sequential" and "concomitant" regimens, including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. AIM To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after non-bismuth quadruple-containing treatment failure. DESIGN prospective multicenter study. PATIENTS in whom a non-bismuth quadruple regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. INTERVENTION levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. OUTCOME eradication was confirmed with (13)C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI 66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%, respectively. Adverse effects were reported in six (6%) patients; all of them were mild. CONCLUSION Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous non-bismuth quadruple "sequential" or "concomitant" treatment failure.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) , Madrid, Spain.
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Gisbert JP, Pérez-Aisa A, Bermejo F, Castro-Fernández M, Almela P, Barrio J, Cosme A, Modolell I, Bory F, Fernández-Bermejo M, Rodrigo L, Ortuño J, Sánchez-Pobre P, Khorrami S, Franco A, Tomas A, Guerra I, Lamas E, Ponce J, Calvet X. Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients. J Clin Gastroenterol 2013; 47:130-135. [PMID: 22647827 DOI: 10.1097/mcg.0b013e318254ebdd] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. AIM To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. DESIGN Prospective multicenter study. PATIENTS In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. INTERVENTION Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. OUTCOME Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). CONCLUSIONS Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, La Princesa, Instituto de Investigación Sanitaria Princesa (IP) y, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
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Shah A, Javid G, Zargar SA, Teli F, Khan BA, Yattoo GN, Gulzar GM, Sodhi JS, Khan MA, Shoukat A, Saif R. Safety and efficacy of 1-week levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori-related peptic ulcer disease in Kashmir, India. Indian J Gastroenterol 2013; 32:32-36. [PMID: 23224792 DOI: 10.1007/s12664-012-0285-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2011] [Accepted: 11/13/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVES There is no ideal therapy for eradication of Helicobacter pylori infection. We evaluated the efficacy and safety of 1-week triple therapy with rabeprazole, levofloxacin, and tinidazole in a metronidazole resistance prevalent region for eradicating H. pylori infection in patients with gastroduodenal ulcers. METHODS This was an open-label, prospective study. Consecutive patients with endoscopy-proven duodenal or gastric ulcer and who were H. pylori-positive were treated with levofloxacin 500 mg once a day, rabeprazole 20 mg twice a day, and tinidazole 500 mg twice daily for 7 days followed by rabeprazole 20 mg OD for 8 weeks. Endoscopy was repeated 8 weeks after the end of therapy to check for ulcer healing and H. pylori status. RESULTS One hundred and thirty-one patients with gastroduodenal ulcers (duodenal 118, and gastric 13) were included. Drug compliance was 97.7 %. The eradication rate of H. pylori by intention-to-treat analysis was 85.5 % (95 % confidence interval 79.5-91.5) (112 of 131 patients) and by per-protocol analysis was 91.8 % (95 % confidence interval 86.9-96.7) (112 of 122 patients). Adverse effects were reported in 17 %: abdominal pain in 3.05 %, metallic taste in 6.87 %, and nausea and vomiting in 4.58 %. CONCLUSIONS Levofloxacin-tinidazole-based triple therapy was highly effective and safe as a first-line regimen in Indian patients with gastroduodenal ulcer disease associated with H. pylori infection. The regimen was well tolerated.
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Affiliation(s)
- Altaf Shah
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India
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Cerqueira RM, Correia MR, Fernandes CD, Vilar H, Manso MC. Cumulative Helicobacter pylori Eradication Therapy in Obese Patients Undergoing Gastric Bypass Surgery. Obes Surg 2012; 23:145-9. [DOI: 10.1007/s11695-012-0747-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Segarra-Newnham M, Coakley C. Salvage Options for Eradication of Helicobacter pylori During Tetracycline Backorder. J Pharm Technol 2012. [DOI: 10.1177/875512251202800502] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Objective: To review salvage options for Helicobacter pylori eradication regimens during a tetracycline backorder for patients with triple-therapy failure. Data Sources: A search of PubMed (1980-June 2012) was conducted using a combination of the terms H. pylori or Helicobacter pylori, salvage therapy, and eradication or treatment as text word searches. Study Selection and Data Extraction: Clinical trials and meta-analyses published in English were included. A manual review of the bibliographies of available literature was conducted and relevant articles were reviewed for inclusion. Data Synthesis: Treatment of H. pylori consists of a triple-drug regimen that includes a proton pump inhibitor (PPI), amoxicillin or metronidazole, and clarithromycin. Failure with this therapy is becoming increasingly common due to macrolide resistance. Upon failure with this regimen, it is recommended that a quadruple regimen with bismuth subsalicylate, metronidazole, tetracycline, and a histamine2 receptor antagonist or a PPI be used. Recent backorders by the 2 manufacturers for tetracycline restrict the use of this regimen. Options that can be considered include minocycline or doxycycline in place of tetracycline, levofloxacin- or moxifloxacin-based regimens, a tinidazole-based regimen, or a rifabutin-based regimen. This article includes a review of 1 study each of minocycline and doxycycline, 5 levofloxacin studies (including meta-analyses), 2 moxifloxacin studies, 1 rifabutin study, and 1 tinidazole study. There are limited data with other tetracyclines; however, given the resistance to quinolones in some areas and possible drug interactions and adverse effects from rifabutin, minocycline or doxycycline regimens may be a better second-line regimen option. Conclusions: Given the current tetracycline shortage, minocycline and doxycycline are options to be considered in patients with a macrolide-based treatment failure. Fluoroquinolones may be an option for patients who have not received these drugs for other indications in the recent past or in areas where resistance is low.
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Affiliation(s)
- Marisel Segarra-Newnham
- MARISEL SEGARRA-NEWNHAM PharmD MPH FCCP BCPS, Clinical Pharmacy Specialist in Infectious Diseases, Veterans Affairs Medical Center, West Palm Beach, FL
| | - Christina Coakley
- CHRISTINA COAKLEY PharmD, at time of writing, PGY1 Pharmacy Resident; now, PGY2 Cardiology Pharmacy Resident, Veterans Affairs Medical Center, West Palm Beach
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Chang WL, Kao CY, Wu CT, Huang AH, Wu JJ, Yang HB, Cheng HC, Sheu BS. Gemifloxacin can partially overcome quinolone resistance of H. pylori with gyrA mutation in Taiwan. Helicobacter 2012; 17:210-5. [PMID: 22515359 DOI: 10.1111/j.1523-5378.2012.00935.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUNDS The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori. MATERIALS AND METHODS Forty-four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin-sensitive controls were tested for gemifloxacin sensitivity by E-test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) > 1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance. RESULTS All levofloxacin-sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5-time lower in MIC levels against levofloxacin-resistant isolates. Nearly all levofloxacin-resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high-level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin-sensitive and levofloxacin-resistant. The gemifloxacin-resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p <.05). CONCLUSION Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.
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Affiliation(s)
- Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Gisbert JP. Rescue Therapy for Helicobacter pylori Infection 2012. Gastroenterol Res Pract 2012; 2012:974594. [PMID: 22536225 PMCID: PMC3299261 DOI: 10.1155/2012/974594] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Accepted: 12/10/2011] [Indexed: 12/18/2022] Open
Abstract
Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final-overall-eradication rate. The choice of a "rescue" treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third-line "rescue" option. Alternatively, it has recently been suggested that levofloxacin-based "rescue" therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line "rescue" option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several "rescue" therapies are consecutively given.
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Affiliation(s)
- Javier P. Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
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Sitafloxacin resistance in Helicobacter pylori isolates and sitafloxacin-based triple therapy as a third-line regimen in Japan. Int J Antimicrob Agents 2012; 39:352-5. [PMID: 22321702 DOI: 10.1016/j.ijantimicag.2011.12.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Revised: 11/29/2011] [Accepted: 12/01/2011] [Indexed: 12/29/2022]
Abstract
The third-line treatment regimen for Helicobacter pylori after failure of clarithromycin- and metronidazole-based therapies is not yet established. Sitafloxacin (STX) is a quinolone that possesses potent in vitro activity against H. pylori. In this study, the susceptibility of H. pylori isolates to STX was examined and the efficacy of STX-based triple therapy as a third-line regimen was evaluated. STX showed minimum inhibitory concentrations (MICs) of ≤1 μg/mL against all 100 H. pylori isolates, and the MIC(90) (MIC for 90% of the organisms) of STX was 5 log(2) dilutions lower than that of levofloxacin (LVX). The MIC(50) (MIC for 50% of the organisms) of STX against gyrA mutants was 0.12 μg/mL and was significantly lower than that of LVX (8 μg/mL). The activity of STX at pH 5.5 was significantly less than that at pH 7.0. In the clinical trial, 28 patients with two eradication failures were treated with STX-based triple therapy [rabeprazole 10 mg twice daily (b.i.d.), amoxicillin 750 mg b.i.d. and STX 100mg b.i.d. for 7 days]. The eradication rate was 75% using intention-to-treat analysis and 80% using per-protocol analysis. Two gyrA mutant strains were eradicated. Amongst participants, a low pepsinogen I/II ratio was associated with successful eradication. These results suggest that STX could be active against most clinical H. pylori isolates and that STX-based triple therapy is a promising and safe third-line therapy.
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Park HK, Lee DH, Suh S, Seo PJ, Kim N, Jeong SH, Kim JW, Hwang JH, Park YS, Lee SH, Shin CM. Dual therapy trial using esomeprazole and amoxicillin as third-line rescue therapy for Helicobacter pylori infection. Clin Endosc 2011; 44:33-7. [PMID: 22741110 PMCID: PMC3363043 DOI: 10.5946/ce.2011.44.1.33] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 08/16/2011] [Accepted: 08/31/2011] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS The purpose of this study was to evaluate the efficacy and tolerability of dual therapy consisting of esomeprazole and amoxicillin as a rescue therapy for Helicobacter pylori infection. METHODS From December 2009 to August 2010, 21 patients who experienced two consecutive eradication failures were included. They received esomeprazole (40 mg, b.i.d.) and amoxicillin (1,000 mg, b.i.d.) for 14 days as a third eradication regimen. Compliance and side effects were determined from an interview. H. pylori status was evaluated using the (13)C urea breath test at least 6 weeks after treatment. RESULTS The mean age of the patients was 59 years and included 52% males. Indications for treatment were functional dyspepsia (61.9%), peptic ulcer disease (28.6%), and gastric adenoma (9.5%). H. pylori was eradicated in 14 of 21 (66.7%) patients. Minor side effects were reported in three of the 21 patients (14.3%). These side effects consisted mainly of nausea and epigastric discomfort. CONCLUSIONS A 2-week course of dual therapy failed to show satisfactory results in third-line H. pylori eradication, but it was very safe and tolerable. Therefore, dual therapy constitutes an encouraging empirical strategy for the elderly and infirm patients with multiple previous eradication failures.
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Affiliation(s)
- Hyun Kyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Helicobacter pylori eradication by sitafloxacin-lansoprazole combination and sitafloxacin pharmacokinetics in Mongolian gerbils and its in vitro activity and resistance development. Antimicrob Agents Chemother 2011; 55:4261-6. [PMID: 21730117 DOI: 10.1128/aac.01105-10] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A total of 293 strains of Helicobacter pylori, including strains resistant to levofloxacin, clarithromycin, metronidazole, or amoxicillin, were examined for in vitro susceptibility to 10 antimicrobial agents. Among these agents, sitafloxacin (a fluoroquinolone) showed the greatest activity (MIC(90), 0.06 μg/ml), with high bactericidal activity and synergy in sitafloxacin-lansoprazole (a proton pump inhibitor) combination. In a Mongolian gerbil model with a H. pylori ATCC 43504 challenge, marked eradication effects were observed at ≥1 mg/kg for sitafloxacin, ≥10 mg/kg for levofloxacin, and ≥10 mg/kg for lansoprazole, reflecting MIC levels for each agent (0.008, 0.25, and 2 μg/ml, respectively). The therapeutic rates were 83.3% for the sitafloxacin (0.3 mg/kg)-lansoprazole (2.5 mg/kg) combination and 0% for either sitafloxacin or lansoprazole alone. The maximum serum concentration (C(max)) of sitafloxacin was 0.080 ± 0.054 μg/ml at 30 min, when orally administered at 1 mg/kg. The simultaneous administration of lansoprazole resulted in no difference. In the resistance development assay, MICs of levofloxacin increased 64- to 256-fold with gyrA mutations (Ala88Pro and Asn87Lys), while MICs of sitafloxacin only up to 16-fold with the Asn87Lys mutation. The data suggest that sitafloxacin exhibited superior anti-H. pylori activity with low rates of resistance development in vitro and that, reflecting high in vitro activities, sitafloxacin-lansoprazole combination exhibited strong therapeutic effects in Mongolian gerbils with a C(max) of sitafloxacin that was 10-fold higher than the MIC value at a 1-mg/kg administration.
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Santoro CM, Bush K, Abbanat D. Characterisation of Staphylococcus aureus and Enterococcus faecalis mutants with reduced susceptibility to the investigational oxazolidinone RWJ-416457. Int J Antimicrob Agents 2010; 36:424-9. [DOI: 10.1016/j.ijantimicag.2010.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2010] [Revised: 06/30/2010] [Accepted: 07/12/2010] [Indexed: 10/19/2022]
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Gisbert JP, Pérez-Aisa A, Castro-Fernández M, Barrio J, Rodrigo L, Cosme A, Gisbert JL, Marcos S, Moreno-Otero R. Helicobacter pylori first-line treatment and rescue option containing levofloxacin in patients allergic to penicillin. Dig Liver Dis 2010; 42:287-290. [PMID: 19632166 DOI: 10.1016/j.dld.2009.06.007] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2009] [Revised: 05/25/2009] [Accepted: 06/10/2009] [Indexed: 02/07/2023]
Abstract
AIM To assess the efficacy and tolerability of Helicobacter pylori first-line treatment (omeprazole-clarithromycin-metronidazole) and second-line rescue option (omeprazole-clarithromycin-levofloxacin) in patients allergic to penicillin. PATIENTS Prospective multicenter study including consecutive patients allergic to penicillin. Therapy regimens: First-line treatment (50 patients): Omeprazole (20mg b.i.d.), clarithromycin (500 mg b.i.d.) and metronidazole (500 mg b.i.d.) for 7 days. Second-line treatment (15 therapy failures out of the aforementioned 50 patients): Omeprazole (20mg b.i.d.), clarithromycin (500 mg b.i.d.) and levofloxacin (500 mg b.i.d.) for 10 days. OUTCOME VARIABLE Negative (13)C-urea breath test 8 weeks after completion of treatment. RESULTS (1) First-line treatment (omeprazole-clarithromycin-metronidazole): Per-protocol and intention-to-treat eradication rates were 55% (27/49; 95%CI=40-70%) and 54% (27/50; 95%CI=39-69%). Compliance with treatment and follow-up was complete in 98% of cases (one patient was not compliant due to nausea). Adverse events were reported in 5 patients (10%): 4 nausea, 1 diarrhoea. (2) Second-line treatment (omeprazole-clarithromycin-levofloxacin): Per-protocol and intention-to-treat eradication rates were both 73% (11/15; 95%CI=45-92%). Compliance with treatment and follow-up was complete in all the cases. Adverse events were reported in 4 patients (20%), which did not prevent the completion of treatment: Mild nausea (2 patients), and vomiting and myalgias/arthralgias (1 patient). CONCLUSION In H. pylori infected patients allergic to penicillin, the generally recommended first-line treatment with omeprazole, clarithromycin and metronidazole has low efficacy for curing the infection. On the other hand, a levofloxacin-containing regimen (together with omeprazole and clarithromycin) represents an encouraging second-line alternative in the presence of penicillin allergy.
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Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
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Abstract
Helicobacter pylori infection is the main known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. After more than 20 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a 'rescue' treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third-line 'rescue' option. Alternatively, it has recently been suggested that levofloxacin-based 'rescue' therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a third-line 'rescue' option. Finally, rifabutin-based 'rescue' therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several 'rescue' therapies are consecutively given. Therefore, the attitude in H. pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Eisig JN, Silva FM, Barbuti RC, Rodriguez TN, Malfertheiner P, Moraes Filho JPP, Zaterka S. Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication. BMC Gastroenterol 2009; 9:38. [PMID: 19470177 PMCID: PMC2695477 DOI: 10.1186/1471-230x-9-38] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2008] [Accepted: 05/26/2009] [Indexed: 12/12/2022] Open
Abstract
Background Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen. Methods This study included 48 patients with peptic ulcer disease. Helicobacter pylori infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use. Results Only one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI- 89%–99%) and 88% (88–92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-naïve patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002). Conclusion An empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of Helicobacter pylori, particularly in patients that have failed one prior eradication therapy.
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Affiliation(s)
- Jaime N Eisig
- Serviço de Gastroenterologia Clínica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil.
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Kuo CH, Hu HM, Kuo FC, Hsu PI, Chen A, Yu FJ, Tsai PY, Wu IC, Wang SW, Li CJ, Weng BC, Chang LL, Jan CM, Wang WM, Wu DC. Efficacy of levofloxacin-based rescue therapy for Helicobacter pylori infection after standard triple therapy: a randomized controlled trial. J Antimicrob Chemother 2009; 63:1017-1024. [PMID: 19246508 DOI: 10.1093/jac/dkp034] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES This prospective study was designed to determine the efficacy of a levofloxacin-based rescue therapy for Helicobacter pylori infection after failure of standard triple therapies. We also surveyed the predictors of this rescue therapy. PATIENTS AND METHODS From June 2005 to March 2007, 1036 patients infected with H. pylori received standard triple regimens (proton pump inhibitor, clarithromycin and amoxicillin). H. pylori eradication was achieved in 855 (82.5%) subjects. One hundred and sixty-six eradication-failure patients were enrolled and randomly assigned to receive a 7 day eradication therapy with esomeprazole, bismuth subcitrate, tetracycline and metronidazole (EBTM) or esomeprazole, amoxicillin and levofloxacin (EAL). Follow-up endoscopy was done 16 weeks later to assess the treatment response. Patients' response, CYP2C19 genotypes and antibiotic resistances were also examined. RESULTS Intention-to-treat analysis revealed that both groups showed similar eradication rates [EBTM 63.9%; 95% confidence interval (CI): 53.6-74.2 and EAL 69.9%; 95% CI: 60.1-79.7] (P = 0.89). Per-protocol results were EBTM = 84.1% (95% CI: 75.1-93.1) and EAL = 75.3% (95% CI: 65.8-84.8) (P = 0.82). Both regimens had similar compliance (P = 0.32), but the EBTM group had more adverse events (P = 0.27). Logistic regression analysis showed that poor compliance, CYP2C19 homozygous extensive metabolizer genotype and levofloxacin resistance were important predictors for eradication failure. CONCLUSIONS The EAL regimen can achieve an efficacy similar to that of the standard EBTM therapy. It may be very useful in countries where bismuth salts are not available. Compliance, CYP2C19 genotype and resistances to antibiotics may influence the outcome of levofloxacin-based rescue therapy. It seems advisable to reserve levofloxacin for rescue treatment to avoid an increase in the resistance phenomenon.
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Nishizawa T, Suzuki H, Hibi T. Quinolone-Based Third-Line Therapy for Helicobacter pylori Eradication. J Clin Biochem Nutr 2009; 44:119-24. [PMID: 19308265 PMCID: PMC2654467 DOI: 10.3164/jcbn.08-220r] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2008] [Accepted: 09/11/2008] [Indexed: 12/21/2022] Open
Abstract
Currently, a standard third-line therapy for Helicobacter pylori (H. pylori) eradication remains to be established. Quinolones show good oral absorption, no major side effects, and marked activity against H. pylori. Several authors have studied quinolone-based third-line therapy and reported encouraging results, with the reported H. pylori cure rates ranging from 60% to 84%. Resistance to quinolones is easily acquired, and the resistance rate is relatively high in countries with a high consumption rate of these drugs. We recently reported a significant difference in the eradication rate obtained between patients infected with gatifloxacin-susceptible and gatifloxacin-resistant H. pylori, suggesting that the selection of quinolones for third-line therapy should be based on the results of drug susceptibility testing. As other alternatives of third-line rescue therapies, rifabutin-based triple therapy, high-dose proton pump inhibitor/amoxicillin therapy and furazolidone-based therapy have been suggested.
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Affiliation(s)
- Toshihiro Nishizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
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Sitafloxacin and garenoxacin may overcome the antibiotic resistance of Helicobacter pylori with gyrA mutation. Antimicrob Agents Chemother 2009; 53:1720-1. [PMID: 19188389 DOI: 10.1128/aac.00049-09] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Abstract
Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a clarithromycin-based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender.
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Zhou J, Zhang M, Sun LD. Comparison between H pylori eradication rates of two moxifloxacin-based triple therapies. Shijie Huaren Xiaohua Zazhi 2008; 16:2887-2890. [DOI: 10.11569/wcjd.v16.i25.2887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the H pylori eradication rates of two 7-day moxifloxacin-based therapies.
METHODS: In this parallel control study, 52 H pylori-positive patients were divided into EMT (esomeprazole 20 mg bid, moxifloxacin 0.4 g qd, tinidazole 0.5 g bid) group and RMA (ranitidine bismuth citrate capsules 0.4 g bid, moxifloxacin 0.4 g qd, amoxicillin 1.0 g bid) group. The patients in both groups were treated for 7 d. H pylori status was assessed 4 weeks after the end of treatment by 13C urea breath test.
RESULTS: The treatment was completed in all the 52 patients. The rates of H pylori eradication in group EMT and RMA were 83.3% and 79.4%, respectively, and there was no difference between them (χ2 = 0.117, P = 0.521).
CONCLUSION: Seven-day moxifloxacin-based triple therapy is a feasible H pylori eradication regimen.
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Jones KR, Cha JH, Merrell DS. Who's Winning the War? Molecular Mechanisms of Antibiotic Resistance in Helicobacter pylori. CURRENT DRUG THERAPY 2008; 3:190-203. [PMID: 21765819 DOI: 10.2174/157488508785747899] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The ability of clinicians to wage an effective war against many bacterial infections is increasingly being hampered by skyrocketing rates of antibiotic resistance. Indeed, antibiotic resistance is a significant problem for treatment of diseases caused by virtually all known infectious bacteria. The gastric pathogen Helicobacter pylori is no exception to this rule. With more than 50% of the world's population infected, H. pylori exacts a tremendous medical burden and represents an interesting paradigm for cancer development; it is the only bacterium that is currently recognized as a carcinogen. It is now firmly established that H. pylori infection is associated with diseases such as gastritis, peptic and duodenal ulceration and two forms of gastric cancer, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. With such a large percentage of the population infected, increasing rates of antibiotic resistance are particularly vexing for a treatment regime that is already fairly complicated; treatment consists of two antibiotics and a proton pump inhibitor. To date, resistance has been found to all primary and secondary lines of antibiotic treatment as well as to drugs used for rescue therapy.
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Affiliation(s)
- Kathleen R Jones
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA
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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; 27:346-54. [PMID: 17999716 DOI: 10.1111/j.1365-2036.2007.03573.x] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Several 'rescue' therapies have been recommended to eradicate Helicobacter pylori, but they still fail in >20% of the cases, and these patients constitute a therapeutic dilemma. AIM To evaluate the efficacy of different 'rescue' therapies empirically prescribed during 10 years to 500 patients in whom at least one eradication regimen had failed to cure H. pylori infection. DESIGN Prospective single-centre study. PATIENTS Consecutive patients in whom at least one eradication regimen had failed. INTERVENTION Rescue regimens included: (i) quadruple therapy with omeprazole-bismuth-tetracycline-metronidazole; (ii) ranitidine bismuth citrate-tetracycline-metronidazole; (iii) omeprazole-amoxicillin-levofloxacin; and (iv) omeprazole-amoxicillin-rifabutin. Antibiotic susceptibility was unknown (rescue regimens were chosen empirically). OUTCOME Eradication was defined as a negative (13)C-urea breath test 4-8 weeks after completing therapy. RESULTS Five hundred patients were included (76% functional dyspepsia, 24% peptic ulcer). Compliance rates with first-, second- and third-line regimens were 92%, 92%, and 95%, respectively. Adverse effects were reported by 30%, 37%, and 55% of the patients receiving second-, third-, and fourth-line regimens. Overall, H. pylori cure rates with the second-, third-, and fourth-line rescue regimens were 70%, 74%, and 76%, respectively. Cumulative H. pylori eradication rate with four successive treatments was 99.5%. CONCLUSION It is possible to construct an overall treatment strategy to maximize H. pylori eradication, on the basis of administration of four consecutive empirical regimens; thus, performing bacterial culture even after a second or third eradication failure may not be necessary.
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Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa and Ciberehd, Universidad Autónoma, Madrid, Spain.
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Gisbert JP, Bermejo F, Castro-Fernández M, Pérez-Aisa A, Fernández-Bermejo M, Tomas A, Barrio J, Bory F, Almela P, Sánchez-Pobre P, Cosme A, Ortiz V, Niño P, Khorrami S, Benito LM, Carneros JA, Lamas E, Modolell I, Franco A, Ortuño J, Rodrigo L, García-Durán F, O'Callaghan E, Ponce J, Valer MP, Calvet X. Second-line rescue therapy with levofloxacin after H. pylori treatment failure: a Spanish multicenter study of 300 patients. Am J Gastroenterol 2008; 103:71-76. [PMID: 17764498 DOI: 10.1111/j.1572-0241.2007.01500.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM Quadruple therapy is generally recommended as second-line therapy after Helicobacter pylori (H. pylori) eradication failure. However, this regimen requires the administration of four drugs with a complex scheme, is associated with a relatively high incidence of adverse effects, and bismuth salts are not available worldwide anymore. Our aim was to evaluate the efficacy and tolerability of a triple second-line levofloxacin-based regimen in patients with H. pylori eradication failure. DESIGN Prospective multicenter study. PATIENTS in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin had failed. INTERVENTION A second eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. OUTCOME Eradication was confirmed with (13)C-urea breath test 4-8 wk after therapy. Compliance with therapy was determined from the interview and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS Three hundred consecutive patients were included. Mean age was 48 yr, 47% were male, 38% had peptic ulcer, and 62% functional dyspepsia. Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 81% (95% CI 77-86%) and 77% (73-82%). Adverse effects were reported in 22% of the patients, mainly including nausea (8%), metallic taste (5%), abdominal pain (3%), and myalgias (3%); none of them were severe. CONCLUSION Ten-day levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous proton pump inhibitor-clarithromycin-amoxicillin failure, being simple and safe.
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Page RL, Ferguson D, Cantu M. An alternative salvage regimen for Helicobacter pylori-resistant patients with heart failure. Cardiology 2007; 110:112-5. [PMID: 17971660 DOI: 10.1159/000110489] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2007] [Accepted: 06/07/2007] [Indexed: 01/29/2023]
Abstract
Helicobacter pylori infects over 50% of the worldwide population. For eradication, European, Canadian, and American guidelines recommend a regimen consisting of a proton pump inhibitor, clarithromycin, and metronidazole or amoxicillin dosed twice daily for at least 7 days. When this treatment strategy fails, a complex, multidosed bismuth-based quadruple regimen is recommended. Unfortunately, for patients with heart failure, this salvage regimen can be potentially hazardous due to the drug-drug interaction with tetracycline and digoxin, as well as the large salicylate content with bismuth subsalicylate. As H. pylori infection is so prevalent, providers will most likely encounter such a therapeutic dilemma. A safe, effective, and simplistic alternative is a 10-day fluoroquinolone-based regimen consisting of a proton pump inhibitor, levofloxacin and either clarithromycin or amoxicillin. Levofloxacin demonstrates excellent bioavailability, widespread tissue and fluid distribution, extended half-life, limited drug interaction profile, low incidence of side effects, and remarkable activity against H. pylori with minimal primary resistance. Compared to the 7-day quadruple regimen, a 10-day levofloxacin-based regimen demonstrated a greater eradication rate, better tolerability, and a lower rate of therapy discontinuation. We briefly provide a summary of the data regarding this levofloxacin-based regimen and two successful cases from our heart failure clinic.
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Affiliation(s)
- Robert Lee Page
- Department of Clinical Pharmacy, UCHSC, Schools of Pharmacy and Medicine, Denver, CO 80262, USA.
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Gisbert JP, Fernández-Bermejo M, Molina-Infante J, Pérez-Gallardo B, Prieto-Bermejo AB, Mateos-Rodríguez JM, Robledo-Andrés P, González-García G. First-line triple therapy with levofloxacin for Helicobacter pylori eradication. Aliment Pharmacol Ther 2007; 26:495-500. [PMID: 17635384 DOI: 10.1111/j.1365-2036.2007.03384.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND At present, the efficacy of proton pump inhibitor-clarithromycin-amoxicillin regimen is relatively low. AIM To evaluate the efficacy and tolerability of a first-line triple clarithromycin-free regimen including ranitidine bismuth citrate, levofloxacin and amoxicillin. DESIGN Prospective study. PATIENTS Helicobacter pylori-positive patients complaining of dyspeptic symptoms referred for gastroscopy. INTERVENTION Levofloxacin (500 mg b.d.), amoxicillin (1 g b.d.) and ranitidine bismuth citrate (400 mg b.d.) was prescribed for 10 days. OUTCOME Eradication was confirmed by a (13)C-urea breath test 8 weeks after therapy. Compliance with therapy was determined by questioning and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS Sixty-four patients were included (30% peptic ulcer, 70% functional dyspepsia). Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 88.5% (95% CI =78-95%) and 84.4 (74-91%). Adverse effects were reported in 9.5% of the patients, mainly including diarrhoea (7.9%); none of them were severe. CONCLUSION This new 10-day levofloxacin-based combination represents an alternative to clarithromycin-based therapy, as it meets the criteria set for regimens used as primary H. pylori treatment: effectiveness (>80%), simplicity (twice-daily dosing and excellent compliance) and safety (low incidence of adverse effects).
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Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa, Madrid, Spain.
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Cattoir V, Nectoux J, Lascols C, Deforges L, Delchier JC, Megraud F, Soussy CJ, Cambau E. Update on fluoroquinolone resistance in Helicobacter pylori: new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility. Int J Antimicrob Agents 2007; 29:389-96. [PMID: 17303392 DOI: 10.1016/j.ijantimicag.2006.11.007] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2006] [Revised: 11/07/2006] [Accepted: 11/07/2006] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. pylori strains isolated in 2004-2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC(50) = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 91, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a 'test and treat' strategy that can confidently rely on QRDR gyrA sequencing.
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Affiliation(s)
- Vincent Cattoir
- Laboratoire de Bactériologie-Virologie-Hygiène, Centre Hospitalier, Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris XII, Créteil, France
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Gisbert JP, Gisbert JL, Marcos S, Moreno-Otero R, Pajares JM. Levofloxacin- vs. ranitidine bismuth citrate-containing therapy after H. pylori treatment failure. Helicobacter 2007; 12:68-73. [PMID: 17241304 DOI: 10.1111/j.1523-5378.2007.00472.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AIM Ranitidine bismuth citrate and levofloxacin-based regimen may be an alternative to quadruple therapy after Helicobacter pylori eradication failure. Our aim was to compare two 7-day triple second-line regimens containing ranitidine bismuth citrate or levofloxacin. METHODS Patients in whom a first eradication trial with omeprazole-clarithromycin-amoxicillin had failed were randomized to receive 7-day treatment with: 1, ranitidine bismuth citrate (400 mg b.i.d.), tetracycline (500 mg q.i.d.), and metronidazole (250 mg q.i.d.), or 2, levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.). Cure rates were evaluated by (13)C-urea breath test. RESULTS One-hundred patients were included: 50 received the ranitidine bismuth citrate regimen, and 50 the levofloxacin one. Groups were comparable in terms of demographic variables. Two percent of the patients (one in each group) did not return for follow up. Compliance was similar in both groups (90% took all the medications correctly). Side-effects (only mild/moderate) in the two groups were also comparable (38% with ranitidine bismuth citrate and 36% with levofloxacin). Per-protocol cure rates were 69% (95% CI = 54-80%) in the ranitidine bismuth citrate group, and 71% (57-82%) in the levofloxacin one. Intention-to-treat cure rates were, respectively, 68% (59-79%) and 68% (59-79%) (nonstatistically significant differences). CONCLUSIONS Both 7-day ranitidine bismuth citrate- and levofloxacin-containing second-line regimens represent alternatives to quadruple therapy in patients with previous omeprazole-clarithromycin-amoxicillin failure.
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Affiliation(s)
- Javier P Gisbert
- Department of Gastroenterology, La Princesa University Hospital, Universidad Autónoma, Madrid, Spain.
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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; 24:1469-74. [PMID: 17032282 DOI: 10.1111/j.1365-2036.2006.03149.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND In patients with a first eradication failure, a second (rescue) therapy still fails in > 20% of cases. AIM To compare rifabutin and levofloxacin rescue regimens in patients with two consecutive Helicobacter pylori eradication failures. METHODS Patients, in whom first treatment with omeprazole-clarithromycin-amoxicillin and a second trial with omeprazole-bismuth-tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed, received 10 days of treatment with either rifabutin (150 mg b.d.) or levofloxacin (500 mg b.d.), plus amoxicillin (1 g b.d.) and omeprazole (20 mg b.d.). Cure rates were evaluated by the (13)C-urea breath test. RESULTS Twenty patients received rifabutin, and 20 levofloxacin. All the patients returned for follow-up. Compliance in the rifabutin group was 100%. Four patients in the levofloxacin group did not take the medication correctly (in two cases due to adverse effects: myalgia and rash). Side effects in the rifabutin and levofloxacin groups were reported in 60% and 50% of the cases, respectively. Five patients (25%) treated with rifabutin presented with leucopenia, and six (30%) treated with levofloxacin presented with myalgias. Per-protocol cure rates were 45% (95% confidence interval, 26-66%) in the rifabutin group, and 81% (57-93%) in the levofloxacin group (P < 0.05). Intention-to-treat cure rates were, 45% (26-66%) and 85% (64-95%), respectively (P < 0.01). CONCLUSIONS After two previous H. pylori eradication failures, a 10-day triple levofloxacin-based rescue regimen is more effective than the same regimen with rifabutin.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, La Princesa University Hospital, Universidad Autónoma, Madrid, Spain.
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Miyachi H, Miki I, Aoyama N, Shirasaka D, Matsumoto Y, Toyoda M, Mitani T, Morita Y, Tamura T, Kinoshita S, Okano Y, Kumagai S, Kasuga M. Primary levofloxacin resistance and gyrA/B mutations among Helicobacter pylori in Japan. Helicobacter 2006; 11:243-9. [PMID: 16882327 DOI: 10.1111/j.1523-5378.2006.00415.x] [Citation(s) in RCA: 112] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Recent years have witnessed a decrease in the rate of Helicobacter pylori eradication due to antimicrobial resistance, clarithromycin or metronidazole resistance in particular. As one of the alternatives to the standard regimens, levofloxacin-containing therapy has been considered a promising regimen. Nevertheless, there is a little information concerning the prevalence of levofloxacin resistance and this resistance mechanism. MATERIALS AND METHODS Levofloxacin susceptibility was examined using E-test in 507 H. pylori strains clinically isolated in Japan from 2001 to 2004. Mutation patterns in the quinolone resistance-determining regions of the gyrA and gyrB genes were evaluated, performing direct sequencing of 68 levofloxacin-resistant and 50 susceptible strains. RESULTS Primary levofloxacin resistance was found in 76 (15.0%) strains. Fifty-seven (83.8%) of 68 levofloxacin-resistant strains analyzed had point mutations in gyrA at Asn-87 or Asp-91, while seven (14.0%) of 50 susceptible strains had gyrA mutations. There was a significant difference in the occurrence of gyrA mutations between levofloxacin-resistant and -susceptible strains (p < .001). In levofloxacin-resistant strains, the occurrence of gyrA mutations at Asn-87 was most common regardless of minimal inhibitory concentration levels, and that of gyrA mutations at Asp-91 tended to be associated with low-level resistance. A double gyrA mutation at Asn-87 and Asp-91 might have an additional impact. As for gyrB, three (4.4%) of 68 levofloxacin-resistant strains with no susceptible strains had mutations. CONCLUSIONS Primary levofloxacin resistance was common in Japan and primarily related to gyrA mutations at Asn-87 and Asp-91.
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Affiliation(s)
- Hideyuki Miyachi
- Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
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Cianci R, Montalto M, Pandolfi F, Gasbarrini GB, Cammarota G. Third-line rescue therapy for Helicobacter pylori infection. World J Gastroenterol 2006; 12:2313-9. [PMID: 16688818 PMCID: PMC4088063 DOI: 10.3748/wjg.v12.i15.2313] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.
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Saad RJ, Schoenfeld P, Kim HM, Chey WD. Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis. Am J Gastroenterol 2006; 101:488-96. [PMID: 16542284 DOI: 10.1111/j.1572-0241.2006.00637.x] [Citation(s) in RCA: 199] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Levofloxacin-based triple therapy has been suggested as an alternative salvage therapy to bismuth-based quadruple therapy for persistent Helicobacter pylori (H. pylori) infection. METHODS A search of PUBMED, EMBASE, EBM Review databases and abstracts from recent Digestive Disease Week, United European Gastroenterology Week, and European Helicobacter Study Group conferences was performed. Randomized controlled trials (RCTs) comparing levofloxacin-based triple salvage therapy (levofloxacin + amoxicillin + PPI) to bismuth-based quadruple salvage therapy (bismuth + tetracycline + metronidazole + PPI) were selected for meta-analysis. Additionally, all prospective trials evaluating this levofloxacin-based triple therapy as salvage therapy were pooled to analyze optimal levofloxacin treatment duration and dosing. All selected trials confirmed prior treatment failure and post-salvage treatment eradication. RESULTS Four RCTs compared a 10-day regimen of levofloxacin-based triple therapy to 7-day bismuth-based quadruple therapy (n = 391 patients). Levofloxacin-based triple therapy was superior to quadruple therapy (RR = 1.41 [95% CI: 1.25-1.59]). Levofloxacin-based triple therapy was better tolerated than quadruple therapy with a lower incidence of side effects (RR = 0.51 [95% CI: 0.34-0.75]) and side effects prompting discontinuation of therapy (RR = 0.30 [95% CI: 0.10-0.89]). Eleven trials (n = 547 patients) evaluating levofloxacin-based triple therapy demonstrated higher eradication rates with 10-day versus 7-day regimen (87%[95% CI: 82%-92%]vs 68%[95% CI: 62%-74%]) yet eight trials (n = 477 patients) demonstrated no difference with 500 mg daily versus 250 mg b.i.d. dosing of levofloxacin (81%[95% CI: 78%-89%]vs 84%[95% CI: 66%-97%]). CONCLUSIONS A 10-day course levofloxacin triple therapy is more effective and better tolerated than 7-day bismuth-based quadruple therapy in the treatment of persistent H. pylori infection.
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Affiliation(s)
- Richard J Saad
- Department of Medicine, Division of Gastroenterology, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI 48109, USA
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