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Gupta A, Shetty S, Mutalik S, Chandrashekar H R, K N, Mathew EM, Jha A, Mishra B, Rajpurohit S, Ravi G, Saha M, Moorkoth S. Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation. Heliyon 2023; 9:e20406. [PMID: 37810864 PMCID: PMC10550623 DOI: 10.1016/j.heliyon.2023.e20406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/10/2023] Open
Abstract
Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.
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Affiliation(s)
- Ashutosh Gupta
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shiran Shetty
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Srinivas Mutalik
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Raghu Chandrashekar H
- Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Nandakumar K
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Elizabeth Mary Mathew
- School of Pharmacy, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | - Abhishek Jha
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Brahmeshwar Mishra
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Siddheesh Rajpurohit
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Gundawar Ravi
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Moumita Saha
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Sudheer Moorkoth
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
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Rammohan R, Magam SG, Joy M, Natt D, Patel A, Tadikonda A, Desai J, Bunting S, Yost RM, Akande O, Mustacchia P. Unpacking the Racial Gap: Helicobacter pylori Infection Clearance Among Different Racial Groups. Cureus 2023; 15:e43080. [PMID: 37680407 PMCID: PMC10482124 DOI: 10.7759/cureus.43080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2023] [Indexed: 09/09/2023] Open
Abstract
Introduction Helicobacter pylori (H. pylori) is a bacteria causing chronic stomach infections, influenced by various factors, including host traits and bacterial virulence. It uses both urease-dependent and independent mechanisms to survive acidic gastric environments. Management entails diagnosis, treatment, and eradication verification. Combining drugs is key to overcoming resistance and ensuring bacteria elimination, thus preventing recurrence and complications. H. Pylori eradication mitigates gastric cancer risk and alleviates symptoms. Racial disparities persist despite declining H. pylori and gastric cancer incidence in the United States (US). African Americans (AA) have higher gastric cancer risks than non-Hispanic Whites. Addressing these disparities is crucial to protect high-risk populations. Methods This study retrospectively compiled H. pylori infection data from 2009 to 2022, categorized by race. Propensity score matching balanced initial group characteristics before analysis. Chi-squared and odds ratio tests were used on the cohort, with Kaplan Meier and Log Rank methods evaluating disease clearance in ethnic groups. Data were extracted from the Sunrise Electronic Medical Record software, including patient demographics, health details, and treatment specifics. Patients aged 18-65 with H. pylori infection at Nassau University Medical Center, who followed their treatment, were selected. Data were processed using Statistical Package for the Social Sciences (SPSS) and RStudio software. Results The study initially included 10,040 H. pylori-diagnosed patients, with 9,288 meeting the study's criteria after attrition. Predominantly female (64.7%), the cohort was racially diverse. A longer disease clearance time was noted among Hispanics (p=0.044). Binomial logistic regression analysis identified influential factors like high school graduation rates, poverty level income, and language proficiency on disease clearance. An odds ratio analysis further emphasized language barriers (HR 0.346, p=0.043) and education status (HR 0.756, p=0.025) as primary covariates impacting disease clearance, underlining the role of socio-economic factors and language proficiency in health outcomes. Conclusion The study highlights racial disparities in H. pylori clearance rates, particularly among Hispanics, necessitating culturally sensitive interventions. It advocates for improved diagnostics, increased healthcare access, and social determinants of health-focused initiatives. It identifies socio-economic status and language proficiency as key factors impacting health outcomes, calling for actions to bridge these disparities. Addressing these differences can decrease healthcare inequalities and economic burden, improving overall health outcomes and reducing costs associated with H. pylori clearance.
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Affiliation(s)
- Rajmohan Rammohan
- Gastroenterology, Nassau University Medical Center, East Meadow, USA
| | | | - Melvin Joy
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
| | - Dilman Natt
- Internal Medicine, Nassau University Medical Center, East Meadow , USA
| | - Achal Patel
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
| | | | - Jiten Desai
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
| | - Susan Bunting
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
| | - Robert M Yost
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
| | - Olawale Akande
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
| | - Paul Mustacchia
- Gastroenterology and Hepatology, Nassau University Medical Center, East Meadow, USA
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Feng M, Namanja-Magliano H, Rajagopalan S, Mishra T, Ducati RG, Hirsch BM, Kelly L, Szymczak W, Fajardo JE, Sidoli S, Fiser A, Jacobs WR, Schramm VL. MAT Gain of Activity Mutation in Helicobacter pylori Is Associated with Resistance to MTAN Transition State Analogues. ACS Infect Dis 2023; 9:966-978. [PMID: 36920074 DOI: 10.1021/acsinfecdis.2c00644] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Helicobacter pylori is found in the gut lining of more than half of the world's population, causes gastric ulcers, and contributes to stomach cancers. Menaquinone synthesis in H. pylori relies on the rare futalosine pathway, where H. pylori 5'-methylthioadenosine nucleosidase (MTAN) is proposed to play an essential role. Transition state analogues of MTAN, including BuT-DADMe-ImmA (BTDIA) and MeT-DADMe-ImmA (MTDIA), exhibit bacteriostatic action against numerous diverse clinical isolates of H. pylori with minimum inhibitory concentrations (MIC's) of <2 ng/mL. Three H. pylori BTDIA-resistant clones were selected under increasing BTDIA pressure. Whole genome sequencing showed no mutations in MTAN. Instead, resistant clones had mutations in metK, methionine adenosyltransferase (MAT), feoA, a regulator of the iron transport system, and flhF, a flagellar synthesis regulator. The mutation in metK causes expression of a MAT with increased catalytic activity, leading to elevated cellular S-adenosylmethionine. Metabolite analysis and the mutations associated with resistance suggest multiple inputs associated with BTDIA resistance. Human gut microbiome exposed to MTDIA revealed no growth inhibition under aerobic or anaerobic conditions. Transition state analogues of H. pylori MTAN have potential as agents for treating H. pylori infection without disruption of the human gut microbiome or inducing resistance in the MTAN target.
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Affiliation(s)
- Mu Feng
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Hilda Namanja-Magliano
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Saranathan Rajagopalan
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Tanmay Mishra
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Rodrigo G Ducati
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Brett M Hirsch
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Libusha Kelly
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States.,Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Wendy Szymczak
- Department of Pathology, Montefiore-Einstein Medical Center, Bronx, New York 10467, United States
| | - Jorge Eduardo Fajardo
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Simone Sidoli
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Andras Fiser
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - William R Jacobs
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, United States
| | - Vern L Schramm
- Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
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Cortés P, Nelson AD, Bi Y, Stancampiano FF, Murray LP, Pujalte GGA, Gomez V, Harris DM. Treatment Approach of Refractory Helicobacter pylori Infection: A Comprehensive Review. J Prim Care Community Health 2021; 12:21501327211014087. [PMID: 33949229 PMCID: PMC8114244 DOI: 10.1177/21501327211014087] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
H. pylori is the most common infection in the world and is associated with gastrointestinal and extra-gastrointestinal manifestations, including peptic ulcer disease, gastrointestinal bleeding, and lymphoproliferative disorders. Despite being discovered less than half a century ago, antibiotic resistance, exacerbated by medication non-adherence and inefficacy of proton pump inhibitors, has grown substantially, explaining the rising incidence of refractory H. pylori infection. In this review, we discuss risk factors, treatment options, surveillance and follow-up, as well as emerging therapies for refractory H. pylori.
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Affiliation(s)
| | | | - Yan Bi
- Mayo Clinic, Jacksonville, FL, USA
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Gisbert JP. Rifabutin for the Treatment of Helicobacter Pylori Infection: A Review. Pathogens 2020; 10:pathogens10010015. [PMID: 33379336 PMCID: PMC7823349 DOI: 10.3390/pathogens10010015] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 12/17/2020] [Accepted: 12/24/2020] [Indexed: 12/12/2022] Open
Abstract
Nowadays, apart from having to know first-line Helicobacter pylori eradication regimens well, we must also be prepared to face treatment failures. The aim of this review is to summarize the role of rifabutin in the management of H. pylori infection. Bibliographical searches were performed in PubMed. Data on resistance and efficacy of rifabutin-containing regimens on H. pylori eradication were meta-analyzed. Mean H. pylori rifabutin resistance rate (39 studies, including 9721 patients) was 0.13%; when studies only including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.07%). Mean H. pylori eradication rate (by intention-to-treat) with rifabutin-containing regimens (3052 patients) was 73%. Respective cure rates for second-, third-, fourth- and fifth-line therapies, were 79%, 69%, 69% and 72%. Most studies administered rifabutin 300 mg/day, which seemed to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10–12-day regimens are generally recommended. Adverse events to rifabutin treatment in H. pylori studies were relatively infrequent (15%), and severe adverse events were exceptional (myelotoxicity was the most significant, although always reversible). In summary, rifabutin-containing therapy represents an encouraging strategy generally restricted, at present, to patients where previous (usually multiple) eradication regimens have 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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Saracino IM, Pavoni M, Zullo A, Fiorini G, Saccomanno L, Lazzarotto T, Antonelli G, Cavallo R, Borghi C, Vaira D. Rifabutin-Based Triple Therapy Or Bismuth-Based Quadruple Regimen As Rescue Therapies For Helicobacter pylori Infection. Eur J Intern Med 2020; 81:50-53. [PMID: 32646659 DOI: 10.1016/j.ejim.2020.06.029] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/16/2020] [Accepted: 06/25/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND/AIMS H. pylori treatment remains a challenge for clinicians, and a definite quote of patients require two or more treatments. We evaluated the efficacy of rifabutin-based therapy and Pylera® regimen as rescue therapies. METHODS Between January 2016 and December 2019, dyspeptic patients with at least one therapeutic failure observed in clinical practice received either a 12-day rifabutin-based triple therapy (esomeprazole 40 mg and amoxicillin 1 g, both twice daily, and rifabutin 150 mg once daily) or 10-day quadruple therapy with Pylera® (three in one capsule containing 140 mg bismuth subcitrate potassium, 125 mg metronidazole and 125 mg tetracycline). The eradication rates according to previous number of eradication failure therapies were calculated. The role antibiotic resistance pattern in H. pylori isolates was also investigated. RESULTS Data of 423 patients were available. A total of 270 patients were treated with rifabutin-based therapy, and the overall eradication rate was 61.9%. Pylera® therapy was administered to 153 patients and the cure rate was 88.3%. According to the number of previous therapeutic failures, the eradication rate for the rifabutin-based therapy was 68.3% as second-line and further decreased to 63.1% in fourth-line therapy. Following Pylera® regimen, the cure rate was 94.8% in second-line, and remained 89.6% in fourth-line therapy. Efficacy of rifabutin-based and Pylera® therapies significantly decreased when clarithromycin and levofloxacin resistance, respectively, were present. CONCLUSIONS Our data documented a decreasing trend for rifabutin-based therapy efficacy according to previous therapy failures, whilst this did not occur for Pylera®.
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Affiliation(s)
- Ilaria M Saracino
- Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy
| | - Matteo Pavoni
- Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Giulia Fiorini
- Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy
| | - Laura Saccomanno
- Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy
| | - Tiziana Lazzarotto
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Guido Antonelli
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Rossana Cavallo
- Microbiology and Virology Unit, University Hospital 'Città della Salute e della Scienza', Turin, Italy
| | - Claudio Borghi
- Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy
| | - Dino Vaira
- Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy.
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Lee SW, Moon SJ, Kim SH, Jung SH, Song KH, Kim SM, Sung JK, Lee DS. The prolongation effect of ilaprazole-based standard triple therapy for Helicobacter pylori. Medicine (Baltimore) 2020; 99:e22137. [PMID: 32957336 PMCID: PMC7505311 DOI: 10.1097/md.0000000000022137] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Helicobacter pylori (HP) infection causes many diseases, such as peptic ulcers, gastritis and gastric cancer, and MALToma. It has been gradually accepted that all HP-infected patients should be treated because HP is regarded as an infection. Therefore, the importance of selecting the optimal treatment regimen has increased. Although the 14-day standard triple therapy (STT) is recommended in the current guidelines, prolonging treatment duration is controversial in real practice because of inconsistent results from previous data and the risk of adverse effects. Additionally, the effect of STT using ilaprazole has not been reported until now. We aimed to compare the eradication rate between 7 and 10 days STT using ilaprazole. METHODS A prospective randomized controlled trial was conducted, which was divided into 2 treatment groups: the control group was 7 days of STT, and the test group was 10 days of STT. The eradication regimen was 10 mg ilaprazole, 500 mg clarithromycin, and 1000 mg amoxicillin twice daily. We included patients who were diagnosed with positive results of H pylori examination. We compared the HP eradication rate according to treatment duration, CYP2C19 subtype and endoscopic diagnosis. RESULTS We enrolled a total of 254 patients consisting of 127 patients in each treatment arm. The eradication rates of the control and test groups were 65.4% (82/127) and 74.8% (95/127), respectively, in the intention-to-treat analysis (P = .1). In the per-protocol analysis, 70.3% (83/118) and 82.6% (94/115) were eradicated in each group, which was statistically significant (P = .027). The CYP2C19 subtype was examined in 230 patients. The eradication rate was 79.2% (57/72), 75.4% (92/122), and 72.2% (26/36) in each group, which was not significantly different (P = .704). CONCLUSION Ten-day STT was more effective than 7-day STT for HP eradication. The eradication rate was not affected by the CYP2C19 genotype.
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Affiliation(s)
- Seung Woo Lee
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul
| | - Sung Jin Moon
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul
| | - Sae Hee Kim
- Division of Gastroenterology Department of Internal Medicine, College of Medicine, Eulji University
| | - Sung Hee Jung
- Division of Gastroenterology Department of Internal Medicine, College of Medicine, Eulji University
| | - Kyung Ho Song
- Division of Gastroenterology Department of Internal Medicine, College of Medicine, Konyang University
| | - Sun Moon Kim
- Division of Gastroenterology Department of Internal Medicine, College of Medicine, Konyang University
| | - Jae Kyu Sung
- Division of Gastroenterology Department of Internal Medicine, Chungnam National University School of Medicine, Republic of Korea
| | - Dong Soo Lee
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul
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8
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Kim YJ, Chung WC. Eradication Therapy for Helicobacter pylori with Diagnostic Test for Clarithromycin Resistance. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2019. [DOI: 10.7704/kjhugr.2019.0019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Miftahussurur M, Waskito LA, Syam AF, Nusi IA, Siregar G, Richardo M, Bakry AF, Rezkitha YAA, Wibawa IDN, Yamaoka Y. Alternative eradication regimens for Helicobacter pylori infection in Indonesian regions with high metronidazole and levofloxacin resistance. Infect Drug Resist 2019; 12:345-358. [PMID: 30774400 PMCID: PMC6362932 DOI: 10.2147/idr.s187063] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background The prevalence of Helicobacter pylori resistance to metronidazole and clarithromycin is high in Indonesia. Moreover, the increasing levofloxacin resistance rates in the absence of bismuth treatment in Indonesia has led to the use of other antibiotics as alternative regimens. Methods We determined the minimum inhibitory concentrations (MICs) of five alternative antibiotics for H. pylori (rifaximin, rifabutin, furazolidone, garenoxacin, and sitafloxacin) using the agar dilution method and assessed mutations associated with antibiotic resistance using next-generation sequencing. Result Analysis of 106 strains isolated from 1039 adult dyspeptic patients revealed that none of the strains were furazolidone-resistant. All strains were also sensitive to rifabutin and sitafloxacin. In contrast, the rates of resistance to rifaximin and garenoxacin were high (38.9% and 6.7%, respectively). The strains isolated from patients on Java Island had the highest resistance rates to garenoxacin and rifaximin. In addition, the resistance was distributed evenly among the ethnic groups, ranging between 25.0% and 69.2%. Except for rifaximin, for which the resistance rate was 38.9%, the other four antibiotics could be successfully employed to eradicate levofloxacin- and metronidazole-resistant H. pylori infections in vitro. Interestingly, garenoxacin-sensitive strains were found in regions with high clarithromycin resistance rates such as Bali and Papua Islands. In contrast, rifaximin might not be considered as an alternative antibiotic in regions with high clarithromycin resistance. There was an inconsistent association between gyrA and gyrB mutations and garenoxacin resistance. We confirmed that the I837V (replacement of isoleucine at position 837 with valine), A2414T/V, Q2079K and K2068R were the predominant rpoB point mutations. There was an association between vacA genotypes of H. pylori and rifaximin resistance (P = 0.048). Conclusion furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as alternative regimens to eradicate H. pylori in Indonesia, including regions with high metronidazole and clarithromycin resistance rates. Moreover, sitafloxacin but not garenoxacin should be considered for eradication of levofloxacin-resistant strains.
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Affiliation(s)
- Muhammad Miftahussurur
- Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia, .,Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia,
| | - Langgeng Agung Waskito
- Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia, .,Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Japan,
| | - Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia
| | - Iswan Abbas Nusi
- Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia,
| | - Gontar Siregar
- Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan 20136, Indonesia
| | - Marselino Richardo
- Department of Internal Medicine, Merauke City General Hospital, Merauke 99656, Indonesia
| | - Achmad Fuad Bakry
- Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Sriwijaya University, Palembang 30126, Indonesia
| | - Yudith Annisa Ayu Rezkitha
- Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia, .,Department of Internal Medicine, Muhammadiyah University of Surabaya, Surabaya 60113, Indonesia
| | - I Dewa Nyoman Wibawa
- Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Udayana, Denpasar 80232, Indonesia
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Japan, .,Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA, .,Global Oita Medical Advanced Research Center for Health, Yufu 879-5593, Japan,
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Ram M. R, Teh X, Rajakumar T, Goh KL, Leow AHR, Poh BH, Mariappan V, Shankar EM, Loke MF, Vadivelu J. Polymorphisms in the host CYP2C19 gene and antibiotic-resistance attributes ofHelicobacter pyloriisolates influence the outcome of triple therapy. J Antimicrob Chemother 2018; 74:11-16. [DOI: 10.1093/jac/dky401] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 09/05/2018] [Indexed: 12/11/2022] Open
Affiliation(s)
- Ravishankar Ram M.
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- Department of Molecular Biology and Genetics, Faculty of Science, University of South Bohemia, Branišovská 31, České Budějovice (Budweis), Czech Republic
| | - Xinsheng Teh
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Tamayanthi Rajakumar
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Khean Lee Goh
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Alex Hwong Ruey Leow
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Bee Hoon Poh
- BP Diagnostic Centre Sdn Bhd, Ipoh, Perak, Malaysia
| | - Vanitha Mariappan
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Esaki M Shankar
- Division of Infection Biology and Medical Microbiology, Department of Life Sciences, Central University of Tamil Nadu (CUTN), Thiruvarur, India
| | - Mun Fai Loke
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- School of Life Sciences & Chemical Technology, Ngee Ann Polytechnic, Singapore, Singapore
| | - Jamuna Vadivelu
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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11
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An Y, Wang Y, Wu S, Wang YH, Qian X, Li Z, Fu YJ, Xie Y. Fourth-generation quinolones in the treatment of Helicobacter pylori infection: A meta-analysis. World J Gastroenterol 2018; 24:3302-3312. [PMID: 30090010 PMCID: PMC6079288 DOI: 10.3748/wjg.v24.i29.3302] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 05/12/2018] [Accepted: 06/16/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the efficacy and safety of fourth-generation quinolones for Helicobacter pylori (H. pylori) eradication, we conducted this systematic review and meta-analysis of randomized clinical trials. METHODS Major literature databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of H. pylori eradication therapies and included fourth-generation quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed. RESULTS Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat (ITT) analysis [75.4% vs 81.8%; odds ratio (OR) = 0.661; 95% confidence interval (CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by per-protocol analysis (79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis (30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies (84.3% vs 71.9%) and in Asian vs European groups (76.7% vs 89.1%). CONCLUSION Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of H. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.
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Affiliation(s)
- Ying An
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Key Laboratory of Digestive Diseases of Jiangxi, Nanchang 330000, Jiangxi province, China
- School of Pharmacy, Nanchang University, Nanchang 330000, Jiangxi province, China
| | - Ya Wang
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Key Laboratory of Digestive Diseases of Jiangxi, Nanchang 330000, Jiangxi province, China
- School of Pharmacy, Nanchang University, Nanchang 330000, Jiangxi province, China
| | - Shuang Wu
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Key Laboratory of Digestive Diseases of Jiangxi, Nanchang 330000, Jiangxi province, China
| | - You-Hua Wang
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Key Laboratory of Digestive Diseases of Jiangxi, Nanchang 330000, Jiangxi province, China
| | - Xing Qian
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Key Laboratory of Digestive Diseases of Jiangxi, Nanchang 330000, Jiangxi province, China
| | - Zhen Li
- Medical College, Nanchang University, Nanchang 330000, Jiangxi province, China
| | - Ying-Jun Fu
- School of Pharmacy, Nanchang University, Nanchang 330000, Jiangxi province, China
| | - Yong Xie
- Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Key Laboratory of Digestive Diseases of Jiangxi, Nanchang 330000, Jiangxi province, China
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Therapeutic efficacy of amoxicillin and rifaximin in patients with small intestinal bacterial overgrowth and Helicobacter pylori infection. GASTROENTEROLOGY REVIEW 2018; 13:213-217. [PMID: 30302165 PMCID: PMC6173078 DOI: 10.5114/pg.2018.74228] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 01/31/2018] [Indexed: 02/07/2023]
Abstract
Introduction Small intestinal bacterial overgrowth (SIBO) may coexist with Helicobacter pylori infection, which can be the cause of chronic gastrointestinal complaints. Aim Evaluation of the therapeutic efficacy of amoxicillin and rifaximin in the treatment of these diseases. Material and methods The lactulose hydrogen breath test (LHBT) and the urea breath test (13C-UBT) were performed in 116 patients. In 62 patients the coexistence of small intestinal bacterial overgrowth and H. pylori infection was observed. Then, in group I (n = 30) pantoprazole (2 × 40 mg), amoxicillin (2 × 1000 mg) and metronidazole (2 × 500 mg) and in group II (n = 32) pantoprazole and amoxicillin at the above doses and rifaximin (3 × 400 mg) were administered for 10 days. After 6 weeks, both breath tests were repeated and the degree of remission of symptoms was measured using a 10-point visual analog scale (VAS). Results After the treatment the LHBT index decreased in group I from 61.2 ±19.4 ppm to 22.0 ±8.2 ppm (p < 0.001) and in group II from 59.6 ±15.5 ppm to 15.2 ±8.6 ppm (p < 0.001). Eradication of H. pylori (13C-UBT below 4.0‰) was achieved in 63.3% of patients in group I and 59.4% in group II (p > 0.05). The decrease of pain below 3.0 points in the VAS was obtained in 64.8% of patients in group I and in 56.2% in group II. Conclusions Combination of amoxicillin and rifaximin may be effective in the treatment of patients with small intestinal bacterial overgrowth syndrome and concomitant H. pylori infection.
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Rodríguez de Santiago E, Martín de Argila de Prados C, Marcos Prieto HM, Jorge Turrión MÃ, Barreiro Alonso E, Flores de Miguel A, de la Coba Ortiz C, Rodríguez Escaja C, Pérez Álvarez G, Ferre Aracil C, Aguilera Castro L, García García de Paredes A, Rodríguez Pérez A, Albillos Martínez A. Limited effectiveness with a 10-day bismuth-containing quadruple therapy (Pylera ® ) in third-line recue treatment for Helicobacter pylori infection. A real-life multicenter study. Helicobacter 2017; 22. [PMID: 28771880 DOI: 10.1111/hel.12423] [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: 12/17/2022]
Abstract
BACKGROUND Helicobacter pylori antibiotic resistance is an increasing problem worldwide. Pylera® may be an option as salvage therapy. AIM To assess the effectiveness, safety, and tolerance of Pylera® as a third-line in clinical practice. MATERIALS AND METHODS This was a multicenter, observational, prospective database study in four Spanish hospitals. Consecutive H. pylori-infected individuals treated with Pylera® and a proton-pump inhibitor (PPI) were invited to participate if they had failed to respond to PPI-clarithromycin-amoxicillin as first-line and to levofloxacin-amoxicillin-PPI as second-line therapy. Eradication was tested 4-8 weeks after Pylera® using a C13 -urea breath test. Treatment-related adverse effects (TRAEs) were assessed through a questionnaire and by reviewing databases. A questionnaire on patient satisfaction was completed in the last visit. RESULTS Of 103 subjects fulfilling the selection criteria, 101 were included in the intention-to-treat (ITT) analysis and 97 in the per-protocol (PP) analysis. A 10 day course was prescribed in all patients. Esomeprazole 40 mg b.i.d. was the most used PPI regimen (ITT=94.1%). Ninety-seven individuals (ITT=96.04%) completed more than 90% of the treatment. Overall eradication rates were ITT=80.2% (95% confidence interval [CI]: 72.3%-88.1%) and PP=84.4% (95% CI: 76.8%-91.8%). One or more TRAEs were experienced by 67.3% (95% CI: 57.7%-75.7%), all mild or moderate. TRAEs and the number of pills were the main complaints. CONCLUSION In an area of high antibiotic resistance to H. pylori, 10-day Pylera® plus double-dose PPI emerged as an alternative as third-line therapy, although not achieving optimal eradication rates. TRAEs were common but were neither severe nor did they condition compliance.
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Affiliation(s)
- Enrique Rodríguez de Santiago
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain
| | - Carlos Martín de Argila de Prados
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain.,IRYCIS, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Hector Miguel Marcos Prieto
- Gastroenterology department, Hospital Universitario de Salamanca, University of Salamanca, IBSAL, Salamanca, Spain
| | - Miguel Ãngel Jorge Turrión
- Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | | | - Alvaro Flores de Miguel
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain
| | | | - Carlos Rodríguez Escaja
- Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Gustavo Pérez Álvarez
- Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Carlos Ferre Aracil
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain
| | - Lara Aguilera Castro
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain
| | - Ana García García de Paredes
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain
| | - Antonio Rodríguez Pérez
- Gastroenterology department, Hospital Universitario de Salamanca, University of Salamanca, IBSAL, Salamanca, Spain
| | - Agustin Albillos Martínez
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, Spain.,IRYCIS, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
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Talebi Bezmin Abadi A. Helicobacter pylori treatment: New perspectives using current experience. J Glob Antimicrob Resist 2017; 8:123-130. [PMID: 28131855 DOI: 10.1016/j.jgar.2016.11.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/10/2016] [Accepted: 11/20/2016] [Indexed: 02/08/2023] Open
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15
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Regnath T, Raecke O, Enninger A, Ignatius R. Increasing metronidazole and rifampicin resistance of Helicobacter pylori isolates obtained from children and adolescents between 2002 and 2015 in southwest Germany. Helicobacter 2017; 22. [PMID: 27400262 DOI: 10.1111/hel.12327] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increasing antibiotic resistance has been reported for Helicobacter pylori, but data on the prevalence of antibiotic resistance of H. pylori in pediatric patients and the development of resistance over time are sparse. METHODS Data for 610 H. pylori isolates obtained between 2002 and 2015 from gastric biopsies of 582 (mainly treatment-naïve) pediatric patients from southwest Germany were analyzed retrospectively regarding the antibiotic susceptibility determined by Etest and patients' characteristics. RESULTS Overall resistance to metronidazole, clarithromycin, and rifampicin was 28.7%, 23.2%, and 13.3%, respectively, while resistance to amoxicillin was rare (0.8%). Simultaneous resistance to metronidazole and clarithromycin was observed for 7.7% of the isolates, and 2.3% were resistant to metronidazole, clarithromycin, and rifampicin. Differences between primary vs secondary resistance existed for metronidazole (24.7% vs 38.8%, P=.01) and clarithromycin (17.2% vs 54.1%, P=.0001). From 2002-2008 to 2009-2015, resistance to metronidazole increased from 20.8% to 34.4% (P=.003) and to rifampicin from 3.9% to 18.8% (P=.0001); this was not associated with increased numbers of patients previously treated for H. pylori infection in the second study period. In contrast, resistance to clarithromycin did not change significantly over time. Resistance was not associated with age, sex, or family origin in Europe. CONCLUSIONS The considerable antibiotic resistance of H. pylori isolates argues for standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of antibiotic therapy.
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Affiliation(s)
| | - Olaf Raecke
- Children's Hospital, Pediatric Gastroenterology, Klinikum Esslingen, Esslingen, Germany
| | - Axel Enninger
- Center for Pediatric Medicine, Olgahospital, Stuttgart, Germany
| | - Ralf Ignatius
- Laboratory Enders & Partners, Stuttgart, Germany.,Department of Microbiology and Hygiene, Charité, Berlin, Germany
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Hansen PB, Penkowa M. Bismuth adjuvant ameliorates adverse effects of high-dose chemotherapy in patients with multiple myeloma and malignant lymphoma undergoing autologous stem cell transplantation: a randomised, double-blind, prospective pilot study. Support Care Cancer 2016; 25:1279-1289. [PMID: 27966023 DOI: 10.1007/s00520-016-3522-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Accepted: 12/05/2016] [Indexed: 12/22/2022]
Abstract
PURPOSE High-dose chemotherapy prior to autologous stem cell transplantation (ASCT) leads to adverse effects including mucositis, neutropenia and bacteremia. To reduce the toxicity, we treated myeloma and lymphoma patients with peroral bismuth as an adjuvant to chemotherapy to convey cytoprotection in non-malignant cells. METHODS This trial was a prospective, randomised, double-blind, placebo-controlled pilot study of hematological inpatients (n = 50) receiving bismuth or placebo tablets, in order to identify any potential superiority of bismuth on toxicity from chemotherapy. RESULTS We show for the first time that bismuth significantly reduces grade 2 stomatitis, febrile neutropenia and infections caused by melphalan in multiple myeloma, where adverse effects also were significantly linked to gender. In lymphoma patients, bismuth significantly reduces diarrhoea relative to placebo. Also, lymphoma patients' adverse effects were linked to gender. For the first time, bismuth is demonstrated as a safe strategy against chemotherapy's toxicity without interfering with intentional anti-cancer efficiency. Also, we show how gender significantly influences various adverse effects and response to treatment in both multiple myeloma and malignant lymphomas. CONCLUSION These results may impact clinical prevention of chemotherapy's cytotoxicity in certain patient groups, and also, this study may direct further attention towards the impact of gender during the course and treatment outcome of malignant disorders.
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Affiliation(s)
- Per Boye Hansen
- Department of Hematology, Herlev Hospital, University of Copenhagen, 2720, Herlev, Denmark.
- Department of Hematology, University Hospital of Roskilde, DK-4000, Roskilde, Denmark.
| | - Milena Penkowa
- Section for Neuroprotection, Hjerneeksperten, 1718, Copenhagen, Denmark
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17
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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] [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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18
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Modification of drug delivery to improve antibiotic targeting to the stomach. Ther Deliv 2016; 6:741-62. [PMID: 26149788 DOI: 10.4155/tde.15.35] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The obstacles to the successful eradication of Helicobacter pylori infections include the presence of antibiotic-resistant bacteria and therapy requiring multiple drugs with complicated dosing schedules. Other obstacles include bacterial residence in an environment where high antibiotic concentrations are difficult to achieve. Biofilm production by the bacteria is an additional challenge to the effective treatment of this infection. Conventional oral formulations used in the treatment of this infection have a short gastric residence time, thus limiting the duration of exposure of drug to the bacteria. This review summarizes the current research in the development of gastroretentive formulations and the prospective future applications of this approach in the targeted delivery of drugs such as antibiotics to the stomach.
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19
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Ang TL, Fock KM, Ang D, Kwek ABE, Teo EK, Dhamodaran S. The Changing Profile of Helicobacter pylori Antibiotic Resistance in Singapore: A 15-Year Study. Helicobacter 2016; 21:261-5. [PMID: 26774006 DOI: 10.1111/hel.12291] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Antibiotic resistance is an important cause of H. pylori treatment failure. This study aimed to examine the change in H. pylori antibiotic resistance profile in Singapore over the course of 15 years. MATERIALS AND METHODS The study period was from 2000 to 2014. Gastric mucosal biopsies obtained from H. pylori-positive patients were cultured. Antibiotic susceptibility to metronidazole, clarithromycin, levofloxacin, tetracycline, and amoxicillin was tested. The change in resistance rates over time was analyzed. RESULTS A total of 708 H. pylori isolates were cultured. There was a significant increase in resistance rates for metronidazole (2000-2002: 24.8%; 2012-2014: 48.2%; p < .001), clarithromycin (2000-2002: 7.9%; 2012-2014: 17.1%; p = .022), and levofloxacin (2000-2002: 5%; 2012-2014: 14.7%; p = .007). The resistance rates for tetracycline (2000-2002: 5%; 2012-2014: 7.6%) and amoxicillin (2000-2002: 3%; 2012-2014: 4.4%) remained stable. Increase in dual (2000-2002: 6.9%; 2012-2014: 9.4%; p = .479) and triple antibiotic resistance rates (2000-2002: 0; 2012-2014: 7.6%; p < .001) were observed. Overall, the most common dual and triple resistance patterns were metronidazole/clarithromycin (4.4%) and metronidazole/clarithromycin/levofloxacin (1.8%), respectively. CONCLUSIONS Over 15 years, H. pylori resistance rates to metronidazole, clarithromycin and levofloxacin had increased. There was increased resistance to multiple antibiotics.
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Affiliation(s)
- Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Kwong Ming Fock
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Daphne Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Andrew Boon Eu Kwek
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
| | - Subbiah Dhamodaran
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore, Singapore
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Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, Crowe SE, Valasek MA. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016; 43:514-33. [PMID: 26694080 PMCID: PMC5064663 DOI: 10.1111/apt.13497] [Citation(s) in RCA: 535] [Impact Index Per Article: 59.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 05/04/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma. AIM To review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms. METHODS A PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing. RESULTS The prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced. CONCLUSIONS Since the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.
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Affiliation(s)
- I. Thung
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - H. Aramin
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - V. Vavinskaya
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - S. Gupta
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - J. Y. Park
- Department of Pathology and the Eugene McDermott Center for Human Growth and DevelopmentUniversity of Texas Southwestern Medical Center and Children's Medical CenterDallasTXUSA
| | - S. E. Crowe
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - M. A. Valasek
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
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Wu IT, Chuah SK, Lee CH, Liang CM, Lu LS, Kuo YH, Yen YH, Hu ML, Chou YP, Yang SC, Kuo CM, Kuo CH, Chien CC, Chiang YS, Chiou SS, Hu TH, Tai WC. Five-year sequential changes in secondary antibiotic resistance of Helicobacter pylori in Taiwan. World J Gastroenterol 2015; 21:10669-10674. [PMID: 26457027 PMCID: PMC4588089 DOI: 10.3748/wjg.v21.i37.10669] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2015] [Revised: 08/04/2015] [Accepted: 09/02/2015] [Indexed: 02/07/2023] Open
Abstract
AIM: To determine changes in the antibiotic resistance of Helicobacter pylori (H. pylori) in southern Taiwan after failure of first-line standard triple therapy.
METHODS: We analyzed 137 H. pylori-infected isolates from patients who experienced eradication failure after standard first-line triple therapy from January 2010 to December 2014. The H. pylori strains were tested for susceptibility to amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline using the E-test method. The minimal inhibitory concentration (MIC) was determined by the agar dilution test. MIC values of ≥ 0.5, ≥ 1, ≥ 1, ≥ 4 and ≥ 8 mg/L were considered to be the resistance breakpoints for amoxicillin, clarithromycin, levofloxacin, tetracycline and metronidazole, respectively.
RESULTS: A high resistance rate was found for clarithromycin (65%-75%) and metronidazole (30%-40%) among patients who failed first-line standard therapy. The resistance levels to amoxicillin and tetracycline remained very low; however, levofloxacin resistance was as high as 37.5% in 2010 but did not increase any further during the past 5 years. The rates of resistance to these antibiotics did not show a statistically significant upward or downward trend.
CONCLUSION: Antibiotic resistance of H. pylori remains a problem for the effective eradication of this pathogen and its associated diseases in Taiwan. High clarithromycin resistance indicated that this antibiotic should not be prescribed as a second-line H. pylori eradication therapy. Moreover, levofloxacin-based second-line therapy should be used cautiously, and the local resistance rates should be carefully monitored.
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Yazbek PB, Trindade AB, Chin CM, Dos Santos JL. Challenges to the Treatment and New Perspectives for the Eradication of Helicobacter pylori. Dig Dis Sci 2015; 60:2901-12. [PMID: 25999247 DOI: 10.1007/s10620-015-3712-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 05/07/2015] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current treatment of H. pylori infection with antibiotics and proton pump inhibitors has several limitations, including poor adherence and intrinsic patient-related factors, drug resistance, and the absence of adequate treatments. This review summarizes the current therapeutic approaches to eradicating H. pylori, the difficulties associated with its treatment, and several new perspectives aimed at improving existing treatment strategies.
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Affiliation(s)
- Priscila Baptistella Yazbek
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Ariane Biolcati Trindade
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Chung Man Chin
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil
| | - Jean Leandro Dos Santos
- School of Pharmaceutical Science, Drugs and Medicines Department, State University of São Paulo "Júlio de Mesquita Filho", Rodovia Araraquara Jaú Km, 01 s/n, Araraquara, SP, 14801-902, Brazil.
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John A, Al Kaabi S, Doiphode S, Chandra P, Sharma M, Babu R, Yacoub R, Derbala M. Does emerging Clarithromycin resistance signal an obituary to empirical standard triple therapy for Helicobacter pylori infection? Indian J Gastroenterol 2015; 34:404-7. [PMID: 26541342 DOI: 10.1007/s12664-015-0604-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2015] [Accepted: 10/16/2015] [Indexed: 02/04/2023]
Abstract
Despite 30 years of its discovery, the ideal therapeutic regimen against Helicobacter pylori is still evasive. Clarithromycin-based standard triple therapy which has been considered the first line empirical therapy has been failing in many parts of the world, due to rising resistance against Clarithromycin, forcing the use of alternate regimens. In this context, we studied the local antibiotic resistance patterns against H. pylori and its impact on standard triple therapy in our region. All patients undergoing diagnostic upper endoscopy during the study period and detected to be positive for rapid urease test (RUT) underwent cultures of gastric mucosal specimens and had their antibiotic resistance patterns mapped out. Standard triple therapy was administered to those tested positive for H. pylori by RUT and eradication rates checked by urea breath test 4 weeks after the completion of treatment. Eradication rates with Clarithromycin-based standard triple therapy were suboptimal with a success of only (71.28%). H. pylori culture and antibiotic susceptibility studies showed high resistance to Clarithromycin (21.2%), Metronidazole (78.1%), and Levofloxacin (15%). However, the resistance to Amoxicillin (2.9%), Tetracycline (0%), and Rifabutin (4.5%) were low. Standard triple therapy is failing in our region due to high Clarithromycin resistance. We need to abandon empirical and blind triple therapy without post-treatment testing and devise alternate effective treatment strategies against H. pylori based on the local resistance patterns observed.
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Affiliation(s)
- Anil John
- Department of Gastroenterology, Hamad Medical Corporation, Doha, Qatar.
| | - Saad Al Kaabi
- Department of Gastroenterology, Hamad Medical Corporation, Doha, Qatar
| | - Sanjay Doiphode
- Department of Microbiology, Hamad Medical Corporation, Doha, Qatar
| | - Prem Chandra
- Department of Medical Research, Hamad Medical Corporation, Doha, Qatar
| | - Manik Sharma
- Department of Gastroenterology, Hamad Medical Corporation, Doha, Qatar
| | - Ragesh Babu
- Department of Gastroenterology, Hamad Medical Corporation, Doha, Qatar
| | - Rafie Yacoub
- Department of Gastroenterology, Hamad Medical Corporation, Doha, Qatar
| | - Moutaz Derbala
- Department of Gastroenterology, Hamad Medical Corporation, Doha, Qatar
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Comparison of Second-Line Quadruple Therapies with or without Bismuth for Helicobacter pylori Infection. BIOMED RESEARCH INTERNATIONAL 2015; 2015:163960. [PMID: 26090383 PMCID: PMC4450213 DOI: 10.1155/2015/163960] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 02/16/2015] [Accepted: 02/16/2015] [Indexed: 12/12/2022]
Abstract
The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide. The non-bismuth-based quadruple therapy or “concomitant therapy” is an alternative option in first-line eradication but has not been used in second-line therapy. Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important. We conducted a randomized controlled trial to compare the efficacies of the standard quadruple therapy and a modified concomitant regimen. One hundred and twenty-four patients were randomly assigned into two groups: RBTM (rabeprozole 20 mg bid., bismuth subcitrate 120 mg qid, tetracycline 500 mg qid, and metronidazole 250 mg qid) and RATM (rabeprozole 20 mg bid., amoxicillin 1 g bid., tetracycline 500 mg qid, and metronidazole 250 mg qid) for 10 days. The eradication rate of the RBTM and RATM regimen was 92.1% and 90.2%, respectively, in intention-to-treat analysis. Patients in both groups had good compliance (~96%). The overall incidence of adverse events was higher in the RATM group (42.6% versus 22.2%, P = 0.02), but only seven patients (11.5%) experienced grades 2-3 events. In conclusion, both regimens had good efficacy, compliance, and acceptable side effects. The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries.
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Mokhtare M, Agah S, Fakheri H, Hosseini V, Rezaei Hemami M, Ghafoori SMS. Efficacy of Clarithromycin Containing Bismuth-Based Regimen as a Second-Line Therapy in Helicobacter Pylori Eradication. Middle East J Dig Dis 2015; 7:75-81. [PMID: 26106466 PMCID: PMC4430795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 01/20/2015] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND The eradication of Helicobacter pylori infection, commonly prevailing in the stomach, has been important since its introduction. Adequate preparations should be made in finding alternatives when faced with first-line treatment failures. Currently, ideal second-line treatments are indistinct and varied among countries as result of different antibiotic resistance patterns. We aimed to evaluate the safety and efficacy of a clarithromycin-containing bismuth-based quadruple regimen as a second-line treatment. METHODS Forty-eight H.pylori-positive patients with proven gastric or duodenal ulcers and/or erosions who had previously failed to respond to furazolidone-containing regimens were enrolled. They received pantoprazole (40 mg-bid), amoxicillin (1gr-bid), bismuth subcitrate (240 mg-bid), and clarithromycin (500mg-bid) for 10 days. Eight weeks after treatment, a (14)C-urea breath test was performed for the re-evaluation of H. pylori eradication. RESULTS Forty-three patients completed the study. H.pylori eradication rates were 79.2% (95% CI=65.00-89.53) and 88.4% (95% CI=74.91-96.11) according to intention-to-treat and per-protocol analyses, respectively. All patients had excellent compliance to treatment and one did not continue therapy because of adverse effects. CONCLUSION In developing countries such as Iran, a ten-day clarithromycin-containing bismuth-based quadruple regimen is encouraged as a second-line treatment because of the acceptable rate of eradication and low adverse effects.
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Affiliation(s)
- Marjan Mokhtare
- 1 Colorectal Research Center (CRRC), Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Shahram Agah
- 1 Colorectal Research Center (CRRC), Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
, Corresponding Author: Shahram Agah, MD Associate professor, Colorectal Research Center (CRRC), Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran Tel: + 98 21 66554790 Fax: +98 21 66526620
| | - Hafez Fakheri
- 2 Inflammatory Diseases of the Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Vahid Hosseini
- 2 Inflammatory Diseases of the Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohsen Rezaei Hemami
- 1 Colorectal Research Center (CRRC), Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Seyed Mohammad Sadegh Ghafoori
- 1 Colorectal Research Center (CRRC), Rasoul Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
,3 Medical Student Research Committee (MSRC),Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Efficacy of Levofloxacin Based Triple and High-Dose PPI-Amoxicillin Dual Eradication Therapy for Helicobacter pylori after Failures of First- and Second-Line Therapies. INTERNATIONAL SCHOLARLY RESEARCH NOTICES 2014; 2014:631501. [PMID: 27379339 PMCID: PMC4897149 DOI: 10.1155/2014/631501] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Revised: 11/14/2014] [Accepted: 12/01/2014] [Indexed: 02/07/2023]
Abstract
Objectives. The aim of this study was to investigate and compare the eradication rate of Helicobacter pylori as the third-line triple therapy with rabeprazole (RPZ) + amoxicillin (AMPC) + levofloxacin (LVFX) and high-dose RPZ + AMPC. Methods. 51 patients who failed Japanese first-line (proton pump inhibitor (PPI) + AMPC + clarithromycin) and second-line (PPI + AMPC + metronidazole) eradication therapy were randomly assigned at a 1 : 1 ratio to one of the following third-line eradication groups: (1) RAL group: RPZ 10 mg (b.i.d.), AMPC 750 mg (b.i.d.), and LVFX 500 mg (o.d.) for 10 days; (2) RA group: RPZ 10 mg (q.i.d.) and AMPC 500 mg (q.i.d.) for 14 days. Patients who failed to respond to third-line eradication therapy received salvage therapy. Results. The rates of eradication success, based on intention to treat (ITT) analysis, were 45.8% in the RAL group and 40.7% in the RA group. The overall eradication rates were 73.9% in the RAL group and 64.0% in the RA group. There was no significant difference between the two groups. Conclusions. The third-line triple therapy with RPZ, AMPC, and LVFX was as effective as that with high-dose RPZ and AMPC.
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Gold BD, Gilger MA, Czinn SJ. New Diagnostic Strategies for Detection of Helicobacter pylori Infection in Pediatric Patients. Gastroenterol Hepatol (N Y) 2014; 10:1-19. [PMID: 26491414 PMCID: PMC4606978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Helicobacter pylori (H pylori) is a common chronic bacterial infection that is an important cause of peptic ulcer disease and gastroduodenal disease in children. H pylori is also associated with extragastric manifestations, including growth reduction, iron-deficiency anemia, and idiopathic thrombocytopenic purpura. Current guidelines recommend endoscopy with biopsy for the definitive demonstration of H pylori infection. In contrast to serology, the fecal antigen test and the urea breath test provide reliable, sensitive, and specific results for detecting active H pylori infection in children before and after treatment. The first-line treatment option for pediatric patients is triple therapy with a proton pump inhibitor and 2 antibiotics, which include amoxicillin and clarithromycin or metronidazole. Decreasing eradication rates and the emergence of antibiotic-resistant strains of H pylori have led to the use of other treatments, such as sequential therapy or triple therapy with newer antibiotics, particularly in geographic areas with high rates of antibiotic resistance. Patients should be tested after treatment to confirm eradication, as the absence of symptoms does not necessarily mean that H pylori is no longer present. This clinical roundtable monograph provides an overview of H pylori infection, as well as expert insight into the diagnosis and management of H pylori infection in children.
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Affiliation(s)
- Benjamin D Gold
- GI Care for Kids, LLC Children's Center for Digestive Healthcare LLC Atlanta, Georgia
| | - Mark A Gilger
- Pediatrician-in-Chief Children's Hospital of San Antonio San Antonio, Texas Professor & Vice Chair Department of Pediatrics Baylor College of Medicine Houston, Texas
| | - Steven J Czinn
- Professor and Chair Department of Pediatrics University of Maryland School of Medicine Physician-in-Chief University of Maryland Children's Hospital Baltimore, Maryland
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Lim HC, Lee YJ, An B, Lee SW, Lee YC, Moon BS. Rifabutin-based high-dose proton-pump inhibitor and amoxicillin triple regimen as the rescue treatment for Helicobacter pylori. Helicobacter 2014; 19:455-61. [PMID: 25231089 PMCID: PMC4284035 DOI: 10.1111/hel.12147] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Rifabutin has been known to be effective in multidrug-resistant Helicobacter pylori-harboring patients undergoing treatment failure for H. pylori infection. AIM To evaluate the efficacy of 7-day treatment regimen consisting rifabutin daily but increasing the dose of amoxicillin and lansoprazole in patients who have failed first and second eradication and to assess the side effect profiles in South Korea. METHODS From December 2007 to May 2013, 59 H. pylori-infected patients with two previous eradication failures were enrolled for this study prospectively. The eligible patients were randomly assigned to either group A or B. Group A received lansoprazole 30 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days, whereas group B received lansoprazole 60 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days. RESULTS In group A, H. pylori eradication was achieved in 25 (78.1%) of the 32 patients in the ITT analysis and in 25 (80.6%) of the 31 patients in the PP analysis. In group B, H. pylori eradication was achieved in 26 (96.3%) of the 27 patients in the ITT analysis and in 27 (100%) of the 26 patients in the PP analysis. There was statistically significant difference between the two groups in terms of the eradication rates in PP analysis (p = .047), whereas a marginally statistical significance was found in terms of the eradication rates in ITT analysis (p = .051). Reported side effects were mild, and treatment was well tolerated. No major changes in physical examination or in standard laboratory parameters were observed after treatment. CONCLUSIONS Rifabutin-based high-dose proton-pump inhibitor (PPI)-combined therapy as empirical rescue treatment is more effective than standard dose PPI-combined rifabutin-based therapy, safe and best tolerable in third-line therapy in the Korean population. The key to successful rescue therapy with rifabutin-amoxicillin-PPI regimen may be to increase doses of PPI.
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Affiliation(s)
- Hyun Chul Lim
- Department of Internal Medicine, Division of Gastroenterology, Yonsei University College of MedicineSeoul, South Korea
| | - Yong Jae Lee
- Department of Family Medicine, Yonsei University College of MedicineSeoul, South Korea
| | - Byoungrak An
- Department of Laboratory Medicine, Yonsei University College of MedicineSeoul, South Korea
| | - Seung Woo Lee
- Department of Internal Medicine, Division of Gastroenterology, Yonsei University College of MedicineSeoul, South Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Division of Gastroenterology, Yonsei University College of MedicineSeoul, South Korea
| | - Byung Soo Moon
- Department of Internal Medicine, Division of Gastroenterology, Yonsei University College of MedicineSeoul, South Korea
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Abstract
PURPOSE OF REVIEW This review focuses on new treatment options for eradicating Helicobacter pylori that have emerged as a result of decreased efficacy of standard triple therapy due to increasing antibiotic resistance. We also report on new data regarding primary and secondary gastric cancer prevention strategies and the potential role of H. pylori as a risk factor for extragastric malignancies. RECENT FINDINGS Treatment options have shifted from triple to various quadruple modifications. The length of therapy duration has, in general, been extended from 7 to 10 and 14 days. Nonbismuth-based quadruple therapies prescribed as sequential, concomitant, and hybrid have shown superiority as compared to standard triple therapy in the eradication of clarithromycin-resistant H. pylori. Bismuth-based quadruple therapy appears almost totally independent of antibiotic resistance and maintains high eradication rates. Levofloxacin is an adequate substitute for clarithromycin and is recommended in second-line regimens. However, it should be used prudently as H. pylori has developed resistance to levofloxacin in many regions of the world. Strategies for primary gastric cancer prevention by H. pylori eradication are effective, whereas H. pylori eradication for secondary gastric cancer prevention is uncertain. Very recent data implicate H. pylori as a risk factor for extragastric malignancies. SUMMARY H. pylori therapy should be tailored according to local antibiotic resistance patterns. In many regions of the world, H. pylori is becoming increasingly resistant to clarithromycin, metronidazole, and levofloxacin. Gastric cancer prevention by H. pylori eradication is most effective, if implemented early in the course of infection. New data are provided which indicate H. pylori as risk factor for extragastric malignancies.
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Hajaghamohammadi A, Safiabadi Tali SH, Samimi R, Oveisi S, Kazemifar AM. Low dose furazolidone for eradication of H- pylori instead of clarithromycin: a clinical trial. Glob J Health Sci 2014; 7:235-9. [PMID: 25560342 PMCID: PMC4796360 DOI: 10.5539/gjhs.v7n1p235] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 06/27/2014] [Indexed: 12/28/2022] Open
Abstract
Background: Helicobacter pylori infection is a common chronic human bacterial infection. Triple- therapy regimen containing a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole is commonly used as first-line treatment for its eradication. However, it may not provide the acceptable eradication rate. The present study was designed to evaluated efficacy of low dose furazolidone with amoxicillin and omeprazole for eradication of H. pylori. Materials and Methods: One hundred twenty patients with non- ulcer dyspepsia or peptic ulcer confirmed by upper GI endoscopy, plus H. pylori infection confirmed by rapid urease test were included in the study. They were randomly divided into two groups, and then received clarithromycin, amoxicillin, and omeprazole, or furazolidone (100 mg PO bid), amoxicillin, and omeprazole. They were evaluated using urea breath test at the end of the study. Findings: The eradication rates were 57.6% and 78.8% in clarithromycin and furazolidone groups, respectively. Their difference was statistically significant (P value 0.013). No side effect was seen in the furazolidone group. Conclusion: Low dose furazolidone rather than clarithromycin can be used as low- cost and effective drug for eradication of H. pylori, in combination with amoxicillin and omeprazole.
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