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Sahara S, Sugimoto M, Murata M, Iwata E, Kawai T, Murakami K, Yamaoka Y, Shimoyama T. Eradication Therapy for Helicobacter pylori Infection in Patients Receiving Hemodialysis: Review. Helicobacter 2024; 29:e13106. [PMID: 38984746 DOI: 10.1111/hel.13106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/15/2024] [Accepted: 06/05/2024] [Indexed: 07/11/2024]
Abstract
Patients receiving hemodialysis (HD) often develop gastrointestinal diseases. Recently, although in general population, clinical guidelines for Helicobacter pylori have strongly recommended its eradication in patients to prevent gastric cancer, optimal eradication regimen and optimal dosage of drugs for patients receiving HD have not been established, due to possible incidence of adverse events. Some antimicrobial agents used in eradication therapy, particularly amoxicillin, can exacerbate renal dysfunction. Given the delayed pharmacokinetics of drugs in patients receiving HD compared with those in healthy individuals, drug regimen and dosage should be considered to minimize adverse effects. Although previous studies have investigated the benefits of eradication therapy for patients receiving HD, because most studies were small in terms of the number of enrolled patients, it is hard to show evidence. The numbers of eradication in HD patients have recently increased, and it is important to provide an optimal regimen. The consideration of eradication in patients undergoing HD with a reduction in the drug dose by 1/2-1/3 may prevent adverse events. Additionally, another important consideration is whether adverse events can be prevented while maintaining a similar eradication rate with reduced drug dosages. Recent meta-analysis findings indicate comparable eradication rates in patients receiving HD and healthy individuals, both with the same dosage regimen and at a reduced dosage regimen, with no significant differences (relative risk [RR] for successful eradication: 0.85 [95% confidence interval (CI): 0.48-1.50]). Unlike with the same dosage regimen (RR for adverse events: 3.15 [95% CI: 1.93-5.13]), the adverse events in the dosage reduction regimen were similar to those in healthy individuals (RR: 1.26 [95% CI: 0.23-6.99]). From a pharmacological perspective, the eradication regimen in patients receiving HD should consider the dosage (1/2-1/3 dosage), dosing number (bid), dosing timing of drugs (after HD), and susceptibility to antimicrobial agents.
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Affiliation(s)
- Shu Sahara
- Department of Gastroenterology, Hamamatsu Medical Center, Hamamatsu, Japan
| | - Mitsushige Sugimoto
- Division of Genome-Wide Infectious Diseases, Research Center for GLOBAL and LOCAL Infectious Disease, Oita University, Yufu, Japan
| | - Masaki Murata
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Eri Iwata
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Japan
| | | | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University, Yufu, Japan
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Sugimoto M, Sahara S, Ichikawa H, Kagami T, Ban H, Otsuka T, Andoh A, Furuta T. Four-times-daily Dosing of Rabeprazole with Sitafloxacin, High-Dose Amoxicillin, or Both for Metronidazole-Resistant Infection with Helicobacter pylori in Japan. Helicobacter 2017; 22. [PMID: 27213463 DOI: 10.1111/hel.12319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition. AIM To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain. METHODS We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a 13 C-urea breath test. RESULTS Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen. CONCLUSION In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q.i.d. and an antibiotic agent (amoxicillin q.i.d. or sitafloxacin b.i.d.) in Japanese patients with metronidazole-resistant strains.
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Affiliation(s)
- Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan.,First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Shu Sahara
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Hitomi Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Takuma Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Hiromitsu Ban
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Taketo Otsuka
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Akira Andoh
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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Ierardi E, Losurdo G, Giorgio F, Iannone A, Principi M, Leo AD. Quinolone-based first, second and third-line therapies for Helicobacter pylori. World J Pharmacol 2015; 4:274-280. [DOI: 10.5497/wjp.v4.i4.274] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 10/08/2015] [Accepted: 11/17/2015] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a very common bacterium that infects about 50% of the world population in urban areas and over 90% of people living in rural and developing countries. Fluoroquinolones, a class of antimicrobials, have been extensively used in eradication regimens for H. pylori. Levofloxacin is the most commonly used, and in second-line regimens, is one of the most effective options. However, an increasing resistance rate of H. pylori to fluoroquinolones is being observed, that will likely affect their effectiveness in the near future. Other novel fluoroquinolone molecules, such as moxifloxacin, sitafloxacin, gatifloxacin and gemifloxacin, have been proposed and showed encouraging results in vitro, although data on their clinical use are still limited. Further studies in large sample trials are needed to confirm their safety and efficacy profile in clinical practice.
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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; 42:477-83. [PMID: 26075959 DOI: 10.1111/apt.13280] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [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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Fakheri H, Bari Z, Aarabi M, Malekzadeh R. Helicobacter pylori eradication in West Asia: A review. World J Gastroenterol 2014; 20:10355-10367. [PMID: 25132752 PMCID: PMC4130843 DOI: 10.3748/wjg.v20.i30.10355] [Citation(s) in RCA: 19] [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] [Received: 09/29/2013] [Revised: 01/08/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
The efficacy of first- and second-line Helicobacter pylori (H. pylori) eradication regimens varies considerably in West Asian countries, mainly due to the variable prevalence of resistant organisms. However, no review article has yet evaluated and compared the efficacy of different regimens among different countries of this region. Therefore, we conducted a review to select the best options and provide recommendations for H. pylori treatment in this geographic region. A search through PubMed was carried out to obtain relevant randomized clinical trials published in English language up to June 2013. According to the results, among different therapeutic regimens used as the first-line protocols, 10-d Bismuth-Furazolidone/Metronidazole quadruple therapy, 14-d Clarithromycin-containing hybrid therapy and 14-d quadruple therapy including a proton pump inhibitor + Bismuth + Tetracycline (500 mg QID) + Metronidazole (500 mg TDS) seemed to be appropriate options. Among second-line therapeutic regimens, Bismuth-based quadruple therapies containing Tetracycline and Furazolidone/Metronidazole, triple therapy containing Amoxicillin and Gatifloxacin and Quadruple therapy including Bismuth + Azithromycin and Ofloxacin seemed to be effective options. Third-line therapies were not evaluated in West Asia; most guidelines, however, recommend choosing optimal eradication regimen according to the pattern of antibiotic susceptibility of H. pylori. Although we limited our investigation to H. pylori eradication regimens in West Asia, the clinical significance of the results goes beyond the countries situated in this geographic region. In fact, the results are transferrable to any region as long as the patterns of resistance are the same.
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Sugimoto M, Uotani T, Sahara S, Ichikawa H, Yamade M, Sugimoto K, Furuta T. Efficacy of tailored Helicobacter pylori eradication treatment based on clarithromycin susceptibility and maintenance of acid secretion. Helicobacter 2014; 19:312-8. [PMID: 24690010 DOI: 10.1111/hel.12128] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Insufficient acid inhibition during Helicobacter pylori eradication treatment and bacterial resistance to antibiotics often causes eradication failure. Four times daily dosing (q.i.d.) of a proton-pump inhibitor (PPI) achieves potent acid inhibition, suggesting its potential usefulness as a regimen for eradicating H. pylori infection. Therefore, a tailored eradication regimen based on antibiotic susceptibility and maintenance of acid inhibition should have a high success rate. We investigated the efficacy of such treatment based on clarithromycin (CAM) susceptibility. METHODS Using 153 H. pylori-positive Japanese patients, we investigated the efficacy of tailored eradication strategy: (1) Patients infected with CAM-sensitive H. pylori were treated with a PPI (rabeprazole 10 mg q.i.d.), amoxicillin 500 mg q.i.d., and CAM 200 mg b.i.d. (n = 89), and (2) patients infected with CAM-resistant were given the same doses of rabeprazole and amoxicillin and metronidazole 250 mg b.i.d. (n = 64) for 1 week. RESULTS In the tailored regimen group, the overall eradication rate was 96.7% (95% CI: 92.5-98.9%, 148/153) in the intention-to-treat (ITT) analysis and 97.4% (93.4-99.3%, 148/152) in the PP analysis. The eradication rates for the CAM- and metronidazole-based treatments were similar (95.5% and 98.4%, respectively, p = .400). The tailored treatment achieved a high eradication rate in CYP2C19 rapid metabolizers who were a resistance genotype for PPI treatment (94.3% (86.0-98.4%, 66/70)). DISCUSSION A tailored H. pylori eradication regimen based on CAM susceptibility and maintaining acid secretion (rabeprazole 10 mg q.i.d.) is useful because it can achieve an eradication rate exceeding 95%, irrespective of eradication history, thus overcoming differences among CYP2C19 genotypes.
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Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
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Sugimoto M, Furuta T. Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype. World J Gastroenterol 2014; 20:6400-6411. [PMID: 24914361 PMCID: PMC4047325 DOI: 10.3748/wjg.v20.i21.6400] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Revised: 12/18/2013] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.
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Wang AY, Peura DA. The prevalence and incidence of Helicobacter pylori-associated peptic ulcer disease and upper gastrointestinal bleeding throughout the world. Gastrointest Endosc Clin N Am 2011; 21:613-35. [PMID: 21944414 DOI: 10.1016/j.giec.2011.07.011] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Due to heightened awareness regarding testing for and eradication of infection, the prevalence and incidence of H pylori infection (and by extension the prevalence and incidence of peptic ulcer disease) appear to have declined in recent years. However, antimicrobial resistance is mounting and traditional clarithromycin- or metronidazole-containing triple therapies may no longer be highly effective at eradicating the infection. Combined bismuth- and metronidazole-containing quadruple therapy or sequential 4-drug therapy may be better choices for first-line treatment against this unique pathogen that is ideally suited to survive in the human stomach.
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Affiliation(s)
- Andrew Y Wang
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA 22908, USA.
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Chiba N. Ulcer Disease and Helicobacter pyloriInfection: Etiology and Treatment. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 2010:102-138. [DOI: 10.1002/9781444314403.ch6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Matsuzaki J, Suzuki H, Tsugawa H, Nishizawa T, Hibi T. Homology model of the DNA gyrase enzyme of Helicobacter pylori, a target of quinolone-based eradication therapy. J Gastroenterol Hepatol 2010; 25 Suppl 1:S7-10. [PMID: 20586870 DOI: 10.1111/j.1440-1746.2010.06245.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Resistance of Helicobacter pylori to the standard therapeutic antimicrobial agents has been demonstrated. Although quinolones are an alternative candidate for third-line eradication therapy, quinolone resistance of H. pylori is also increasing. Quinolone resistance of H. pylori is caused by a point mutation of the DNA gyrase subunit A (GyrA) protein, especially on amino acids 87 and 91. The aim of this study is to surmise the structure of H. pylori GryA. METHODS The modeling of the 3-D structure of H. pylori GyrA was performed by an automated homology modeling program: SWISS-MODEL. The position of amino acids 87 and 91 in H. pylori GyrA was plotted on the homology model. To estimate the function of quinolone resistance-determining region (QRDR), the structure of H. pylori GyrA was compared with Escherichia coli GyrA. RESULTS A molecular model of H. pylori GyrA could be predicted using SWISS-MODEL. The GyrA N- and C-terminal domains closely resembled those of E. coli. The position of amino acids 87 and 91 in H. pylori GyrA was part of the DNA binding region (head dimer interface) on the GyrA N-terminal domain. CONCLUSION Our homology model of H. pylori GryA suggests that the quinolone resistance-determining region is on the head dimer interface of the GyrA N-terminal domain.
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Affiliation(s)
- Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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Transfer and distribution of amoxicillin in the rat gastric mucosa and gastric juice and the effects of rabeprazole. Acta Pharmacol Sin 2010; 31:501-8. [PMID: 20305682 DOI: 10.1038/aps.2009.191] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM To investigate the distribution of amoxicillin in the gastric juice and gastric mucosa of rats and to investigate the effects of proton pump inhibitor rabeprazole on amoxicillin concentrations in various compartments. METHODS One hundred and sixty anesthetized rats were divided into five groups, and given intravenously different doses of amoxicillin or amoxicillin and rabeprazole. The pH value and volume of gastric juice was aspirated were measured and separated gastric mucosa was homogenized. The concentrations of amoxicillin in the plasma, gastric juice and gastric mucosa were measured by high performance liquid chromatography (HPLC). RESULTS The maximum concentrations of amoxicillin in gastric juice and gastric mucosa were significantly lower than those in plasma (P<0.001). Concentrations in the glandular stomach mucosa were higher than those in the forestomach mucosa. Rabeprazole did not significantly change the pharmacokinetic parameters of amoxicillin in the plasma and did not alter gastric antibiotic clearance or the gastric transfer fraction of amoxicillin in gastric juice. However, rabeprazole did increase the amoxicillin concentration and pH value in gastric juice and reduced the volume of the gastric juice. CONCLUSION Amoxicillin could penetrate the gastric mucosa and achieve therapeutic concentrations at the target site after transfer from the blood to the stomach. Rabeprazole increased the amoxicillin concentration in gastric juice by decreasing the gastric juice volume but did not affect its concentration in blood or gastric mucosa.
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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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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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Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy. Arch Immunol Ther Exp (Warsz) 2009; 57:45-56. [PMID: 19219527 DOI: 10.1007/s00005-009-0007-z] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2008] [Accepted: 10/20/2008] [Indexed: 12/11/2022]
Abstract
The cure rates of Helicobacter pylori infection by using a combination of a proton pump inhibitor (PPI) and antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of acid inhibition during the treatment. Currently used empirical triple therapies do not reliably produce a > or =80% cure rate on an intention-to-treat basis. Therefore, tailored regimens based on relevant microbiological findings and pharmacogenomics are recommended for attaining an acceptable > or =95% cure rate. Recently, virulence factors of H. pylori, such as cagA and vacA, are reported to be major factors determining the cure rates. Individuals infected with strains with cagA-negative and vacA s2 genotypes have significantly increased risk of eradication failure of H. pylori infection. These virulence factors enhance gastric mucosal inflammation and are associated with the development of peptic ulcer and gastric cancer. H. pylori virulence factors induce proinflammatory cytokines, such as interleukin (IL)-1, IL-8, and tumor necrosis factor (TNF)- which influence mucosal inflammation and/or gastric acid secretion. When physicians select an H. pylori eradication regimen with an acceptable cure rate, they might need to consider H. pylori virulence factors, especially cagA and vacA.
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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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Nishizawa T, Suzuki H, Nakagawa I, Iwasaki E, Masaoka T, Hibi T. Gatifloxacin-based triple therapy as a third-line regimen for Helicobacter pylori eradication. J Gastroenterol Hepatol 2008; 23 Suppl 2:S167-70. [PMID: 19120892 DOI: 10.1111/j.1440-1746.2008.05407.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM This study was designed to investigate the efficacy of gatifloxacin (GAT)-based triple therapy as a third-line treatment for Helicobacter pylori (H. pylori) eradication, according to the assessment of the susceptibility to GAT and gyrA mutation. METHODS Fourteen patients who had eradication failure following both clarithromycin-based triple therapy and metronidazole-based triple therapy, or who were infected with H. pylori isolates that were resistant to both clarithromycin and metronidazole after failure of clarithromycin-based triple therapy, were enrolled. These patients were randomly assigned to two groups: (i) rabeprazole and amoxicillin (RA) and (ii) rabeprazole, amoxicillin, and GAT for 7 days (RAG). The minimal inhibitory concentrations were determined by the agar dilution method. The gyrA gene was examined by sequencing. RESULTS The eradication rate was 0% in the RA group and 75% in the RAG group. The eradication rate in the RAG group was 100% in patients infected with GAT-susceptible bacteria and/or bacteria without gyrA mutations, but was only 33.3% in those infected with GAT-resistant bacteria or bacteria with gyrA mutations. CONCLUSION Although GAT may be a promising candidate for third-line therapy, its selection must be based on the results of drug susceptibility testing or gyrA analyses.
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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, Japan
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Zhou Q, Yan XF, Zhang ZM, Pan WS, Zeng S. Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: Drug metabolism and its related interactions. World J Gastroenterol 2007; 13:5618-28. [PMID: 17948937 PMCID: PMC4172742 DOI: 10.3748/wjg.v13.i42.5618] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [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 review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of medicines in clinical practice.
METHODS: Relevant literature was identified by performing MEDLINE/Pubmed searches covering the period from 1988 to 2006.
RESULTS: Seven classes of drugs were chosen, including gastric proton pump inhibitors, histamine H2-receptor antagonists, benzamide-type gastroprokinetic agents, selective 5-HT3 receptor antagonists, fluoroquinolones, macrolide antibiotics and azole antifungals. They showed significant differences in metabolic profile (i.e., the fraction of drug metabolized by cytochrome P450 (CYP), CYP reaction phenotype, impact of CYP genotype on interindividual pharmacokinetics variability and CYP-mediated drug-drug interaction potential). Many events of severe adverse drug reactions and treatment failures were closely related to the ignorance of the above issues.
CONCLUSION: Clinicians should acquaint themselves with what kind of drug has less interpatient variability in clearance and whether to perform CYP genotyping prior to initiation of therapy. The relevant CYP knowledge helps clinicians to enhance the management of patients with gastrointestinal disease who may require treatment with polytherapeutic regimens.
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Sugimoto M, Furuta T, Shirai N, Kodaira C, Nishino M, Yamade M, Ikuma M, Watanabe H, Ohashi K, Hishida A, Ishizaki T. Treatment strategy to eradicate Helicobacter pylori infection: impact of pharmacogenomics-based acid inhibition regimen and alternative antibiotics. Expert Opin Pharmacother 2007; 8:2701-17. [PMID: 17956193 DOI: 10.1517/14656566.8.16.2701] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The eradication rates of Helicobacter pylori by the triple therapy consisting of a proton pump inhibitor (PPI) and two antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and magnitude of acid inhibition during the treatment with a PPI. Acid inhibition during the treatment is affected by the dosing schemes of acid inhibitory drugs (i.e., PPI), genotypes of drug-metabolizing enzymes (i.e., CYP450 2C19), drug transporters (i.e., multi-drug resistant transporter-1) and inflammatory cytokines (i.e., IL-1 beta). Modification of dosing schedules of a PPI, such as frequent PPI dosing and concomitant dosing with a histamine 2-receptor antagonist, could overcome these genetics-related differences in therapeutic effectiveness. For attaining higher eradication rates, the tailored regimen based on the relevant pharmacogenomics is preferable.
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Affiliation(s)
- Mitsushige Sugimoto
- Hamamatsu University School of Medicine, First Department of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
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Sugimoto M, Furuta T, Shirai N, Kodaira C, Nishino M, Ikuma M, Ishizaki T, Hishida A. Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy. Helicobacter 2007; 12:317-23. [PMID: 17669104 DOI: 10.1111/j.1523-5378.2007.00508.x] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUNDS AND AIMS Eradication rates of Helicobacter pylori by a proton pump inhibitor-based triple therapy depend on CYP2C19 genotype status. We investigated whether gastric acid inhibition during an eradication therapy would influence the eradication rates attained by the triple therapy. METHODS Thirty-two patients with H. pylori infection underwent the first-line triple therapy with lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 400 mg b.i.d. for 1 week. In all 32 patients, the 24-hour intragastric pH monitoring was performed on day 6 during the treatment period. RESULTS The intention-to-treat-based eradication rate by the first-line therapy was 75.0% (24/32, 95%CI: 56.60-88.54%). In patients with successful eradication, the median 24-hour pH was 6.4 (range; 5.0-7.6), which was significantly higher than that in patients without eradication [5.2 (2.2-6.2), p = .0131]. The median percentage time of pH < 4.0 during 24-hour postdose in patients with eradication [0.5% (0.0-31.6%)] was significantly shorter than that in patients without eradication [26.7% (6.0-72.2%), p = .0017]. These parameters for acid inhibition significantly differed among the different CYP2C19 genotype groups. When the percentage time of pH < 4.0 and 24-hour pH were attained < 10% and > 6.0, respectively, during the eradication treatment, the majority of patients could eradicate H. pylori infection, irrespective of the bacterial susceptibility to clarithromycin. CONCLUSIONS The sustained intragastric pH > 4.0 for a longer postdose time appears to be required for a successful eradication of H. pylori with lansoprazole and acid-labile antibiotics.
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Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
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Moosavian M, Tajbakhsh S, Samarbaf-Zadeh AR. Rapid detection of clarithromycin-resistant Helicobacter pylori in patients with dyspepsia by fluorescent in situ hybridization (FISH) compared with the E-test. Ann Saudi Med 2007; 27:84-8. [PMID: 17356313 PMCID: PMC6077032 DOI: 10.5144/0256-4947.2007.84] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Clarithromycin is the antibiotic of choice for treatment of H.pylori-related dyspepsia, but unfortunately, resistance to clarithromycin is not rare. Detection of resistant strains takes 2 to 4 days by conventional methods. In this report, we applied the FISH technique for rapid detection of H.pylori in biopsies of dyspeptic patients. METHODS Gastric biopsies from 50 patients suffering from dyspepsia were tested in this study. Part of each biopsy specimen was cultured and the remainder was fixed in liquid nitrogen. After mounting of frozen sections on microscopic slides, they were hybridized with oligonucleotide probes for detection of clarithromycin-resistant H.pylori. The slides were visualized under a fluorescent microscope. Susceptibility of cultured strains of H. pylori to clarithromycin was also determined by the E-test and the results were compared. RESULTS Twenty-five of 50 biopsy specimens examined by FISH were positive for H.pylori. FISH showed that 17 strains (68%) were susceptible to clarithromycin and 6 strains (24%) were resistant. Bacteria isolated following culture of 2 biopsy specimens had a mixture of both clarithromycin-susceptible and resistant strains (8%). There was no discrepancy between the E-test and FISH technique for detection of resistant strains of H.pylori. CONCLUSION FISH is a rapid technique for detection of H.pylori in clinical samples. Moreover, strains susceptible to clarithromycin can be detected quickly. Therefore, this method is suitable for determination of susceptibility of H.pylori to clarithromycin, especially when a quick decision is necessary for treating dyspeptic patients.
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Affiliation(s)
- Mojtaba Moosavian
- Department of Microbiology Faculty of Medicine Ahwaz Jundi Shapour University of Medical Sciences Ahwaz, Iran.
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Nishizawa T, Suzuki H, Umezawa A, Muraoka H, Iwasaki E, Masaoka T, Kobayashi I, Hibi T. Rapid detection of point mutations conferring resistance to fluoroquinolone in gyrA of Helicobacter pylori by allele-specific PCR. J Clin Microbiol 2006; 45:303-5. [PMID: 17122023 PMCID: PMC1829027 DOI: 10.1128/jcm.01997-06] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori strains with reduced susceptibility to fluoroquinolones have a mutation at either codon 87 Asn or 91 Asp of the gyrA gene. A rapid test based on an allele-specific PCR (AS-PCR) was designed to detect the gyrA mutations. Clinical H. pylori isolates were obtained from the stomachs of 51 patients with H. pylori infections who showed treatment failure. The MICs of gatifloxacin (GAT) were determined by the agar dilution method. Identical genotyping results were obtained with AS-PCR and conventional PCR. The gyrA mutations of H. pylori causing reduced susceptibility to fluoroquinolones could be detected successfully by this method. A significant association was observed between the presence of mutations, as detected by AS-PCR, and the resistance of the strains to GAT. Moreover, genotyping by AS-PCR took less than 3 to 4 h. The AS-PCR method for the detection of gyrA mutations in H. pylori is useful for easy identification of fluoroquinolone-resistant strains of H. pylori.
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Affiliation(s)
- Toshihiro Nishizawa
- Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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