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Wani FA, Bashir G, Khan MA, Zargar SA, Rasool Z, Qadri Q. Antibiotic resistance in Helicobacter pylori: A mutational analysis from a tertiary care hospital in Kashmir, India. Indian J Med Microbiol 2018; 36:265-272. [PMID: 30084422 DOI: 10.4103/ijmm.ijmm_18_19] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Helicobacter pylori infection is recognised as type 1 carcinogen by the International Agency of Research on Cancer. Previous studies in our hospital have revealed high prevalence of H. pylori in our population with a high recurrence rate after completion of treatment. This prompted us to undertake this study. Aim This study aimed to determine common gene mutations leading to resistance to clarithromycin, metronidazole, tetracycline and quinolones in H. pylori in patients attending our hospital. Settings and Design This is a cross-sectional hospital-based study. The study was approved by the Institutional Ethics Committee. Materials and Methods This study was conducted on 196 adult dyspeptic patients with an indication for upper gastrointestinal endoscopy. Gastric biopsies collected from them were subjected to histopathological examination, rapid urease test (RUT) and culture. Of the 196 patients, 95 met the inclusion criteria. Drug susceptibility testing (DST) by various polymerase chain reaction-based methods was done for 47 RUT-positive biopsies and 13 H. pylori isolates. Results Maximum resistance was seen to metronidazole (81.66%) followed by clarithromycin (45%) and quinolones (3.33%). No high-level resistance was seen to tetracycline. In clarithromycin-resistant cases, A2142G mutation was more prevalent than A2143G mutation. Multidrug resistance (resistance to metronidazole and clarithromycin) was seen in 41.66% of patients. Conclusions Tetracycline and quinolones could be the antibiotics of choice in the eradication of H. pylori in this region, while recurrence of the infection with H. pylori could be expected among patients receiving either metronidazole or clarithromycin, for eradication therapy. DST should be done on a routine basis utilising both phenotypic and genotypic methods to prevent further emergence of resistance in this region.
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Affiliation(s)
- Fayaz Ahmad Wani
- Department of Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Gulnaz Bashir
- Department of Microbiology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Mushtaq Ahmad Khan
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Showkat Ali Zargar
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Zubaida Rasool
- Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Qurteeba Qadri
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
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Hu Y, Zhang M, Lu B, Dai J. Helicobacter pylori and Antibiotic Resistance, A Continuing and Intractable Problem. Helicobacter 2016; 21:349-63. [PMID: 26822340 DOI: 10.1111/hel.12299] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori, a human pathogen with a high global prevalence, is the causative pathogen for multiple gastrointestinal diseases, especially chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric malignancies. Antibiotic therapies remain the mainstay for H. pylori eradication; however, this strategy is hampered by the emergence and spread of H. pylori antibiotic resistance. Exploring the mechanistic basis of this resistance is becoming one of the major research questions in contemporary biomedical research, as such knowledge could be exploited to devise novel rational avenues for counteracting the existing resistance and devising strategies to avoid the development of a novel anti-H. pylori medication. Encouragingly, important progress in this field has been made recently. Here, we attempt to review the current state and progress with respect to the molecular mechanism of antibiotic resistance for H. pylori. A picture is emerging in which mutations of various genes in H. pylori, resulting in decreased membrane permeability, altered oxidation-reduction potential, and a more efficient efflux pump system. The increased knowledge on these mechanisms produces hope that antibiotic resistance in H. pylori can ultimately be countered.
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Affiliation(s)
- Yue Hu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Meng Zhang
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Bin Lu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
| | - Jinfeng Dai
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Dadashzadeh K, Milani M, Rahmati M, Akbarzadeh A. Real-time PCR detection of 16S rRNA novel mutations associated with Helicobacter pylori tetracycline resistance in Iran. Asian Pac J Cancer Prev 2015; 15:8883-6. [PMID: 25374223 DOI: 10.7314/apjcp.2014.15.20.8883] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Tetracycline is an antibiotic widely used for the treatment of Helicobacter pylori infection, but its effectiveness is decreasing due to increasing bacterial resistance. The aim of this study was to investigate the occurrence of 16S rRNA mutations associated with resistance or reduced susceptibility to tetracycline of Helicobacter pylori by real-time PCR (RT-PCR) assays from culture. MATERIALS AND METHODS Tetracycline susceptibility and minimal inhibition concentration (MIC) was determined by the Epsilometer test (Etest) method. A LightCycler assay developed to detect these mutations was applied to DNA extracted from culture. The 16S rRNA of these isolates was sequenced and resistance-associated mutations were identified. From 104 isolates of H. pylori examined, 11 showed resistance to tetracycline. RESULTS LightCycler assay was applied to DNA extracted from 11 tetracycline-susceptible and 11 tetracycline resistance H. pylori isolates. In our study the sequencing of the H. pylori wild types in 16 s rRNA gene were AGA 926-928 with MIC (0.016 to 0.5 μg/ml), while the sequencing and MIC for resistant were GGA and AGC, (0.75 to 1.5 μg/ml), respectively. Also we found a novel mutation in 2 strains with 84° as their melting temperatures and exhibition of an A939C mutation. CONCLUSIONS We conclude that real-time PCR is an excellent method for determination of H. pylori tetracycline resistance related mutations that could be used directly on biopsy specimens.
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Affiliation(s)
- Kianoosh Dadashzadeh
- Department of Laboratory Sciences, Marand Branch, Islamic Azad University, Marand, Iran E-mail :
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Roncarati D, Danielli A, Scarlato V. The HrcA repressor is the thermosensor of the heat-shock regulatory circuit in the human pathogen Helicobacter pylori. Mol Microbiol 2014; 92:910-20. [PMID: 24698217 DOI: 10.1111/mmi.12600] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2014] [Indexed: 01/03/2023]
Abstract
Bacteria exploit different strategies to perceive and rapidly respond to sudden changes of temperature. In Helicobacter pylori the response to thermic stress is transcriptionally controlled by a regulatory circuit that involves two repressors, HspR and HrcA. Here we report that HrcA acts as a protein thermometer. We demonstrate that temperature specifically modulates HrcA binding to DNA, with a complete and irreversible temperature-dependent loss of DNA binding activity at 42°C. Intriguingly, although the reduction of HrcA binding capability is not reversible in vitro, transcriptional analysis showed that HrcA exerts its repressive influence in vivo, even when the de novo repressor synthesis is blocked after the temperature challenge. Accordingly, we demonstrate the central role of the chaperonine GroESL in restoring the HrcA binding activity, lost upon heat challenge. Together our results establish HrcA as a rare example of intrinsic temperature sensing transcriptional regulator, whose activity is post-transcriptionally modulated by the GroESL chaperonine.
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Affiliation(s)
- Davide Roncarati
- Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy
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Patel J, Patil P. Preparation and characterization of amoxicillin mucoadhesive microparticles using solution-enhanced dispersion by supercritical CO2. J Microencapsul 2012; 29:398-408. [DOI: 10.3109/02652048.2012.655329] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
BACKGROUND Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection. AIM To evaluate the role of rifabutin in the treatment of H. pylori infection. METHODS Bibliographical searches were performed in MEDLINE. Data on the efficacy of rifabutin-containing regimens on H. pylori eradication were combined and meta-analysed using the generic inverse variance method. RESULTS Rifabutin shows good in vitro activity against H. pylori. Mean H. pylori rifabutin resistance rate (calculated from 11 studies including 2982 patients) was 1.3% (95% confidence interval = 0.9-1.7%). When only studies including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.6%). On the other hand, higher values of rifabutin resistance were calculated (1.59%) when only post-treatment patients were considered. Overall, mean H. pylori eradication rate (intention-to-treat analysis) with rifabutin-containing regimens (1008 patients) was 73% (67-79%). Respective cure rates for second-line (223 patients), third-line (342 patients) and fourth/fifth-line (95 patients) rifabutin therapies were 79% (67-92%), 66% (55-77%) and 70% (60-79%) respectively. For treating H. pylori infection, almost all studies have administered rifabutin 300 mg/day; this dose seems to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10- to 12-day regimens are generally recommended. The mean rate of adverse effects was 22% (19-25%). Myelotoxicity is the most significant, although this complication was rare. Until now, all patients have recovered of leucopenia uneventfully in a few days, and there have been no reports of infection or other adverse outcomes related to it. CONCLUSION Rifabutin-containing rescue therapy constitutes an encouraging strategy after multiple (usually three) previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
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Hajimahmoodi M, Shams-Ardakani M, Saniee P, Siavoshi F, Mehrabani M, Hosseinzadeh H, Foroumadi P, Safavi M, Khanavi M, Akbarzadeh T, Shafiee A, Foroumadi A. In vitro antibacterial activity of some Iranian medicinal plant extracts against Helicobacter pylori. Nat Prod Res 2011; 25:1059-66. [DOI: 10.1080/14786419.2010.501763] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- M. Hajimahmoodi
- a Department of Drug and Food Control , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran
| | - M. Shams-Ardakani
- b Department of Pharmacognosy, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran
| | - P. Saniee
- c Department of Microbiology, Faculty of Sciences , University of Tehran , Tehran , Iran
| | - F. Siavoshi
- c Department of Microbiology, Faculty of Sciences , University of Tehran , Tehran , Iran
| | - M. Mehrabani
- d Pharmaceutics Research Center, Kerman University of Medical Sciences , Kerman , Iran
| | - H. Hosseinzadeh
- e Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran
| | - P. Foroumadi
- e Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran
| | - M. Safavi
- e Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran
| | - M. Khanavi
- b Department of Pharmacognosy, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran
| | - T. Akbarzadeh
- e Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran
| | - A. Shafiee
- e Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran
| | - A. Foroumadi
- e Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran
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Patel JK, Chavda JR. Formulation and evaluation of stomach-specific amoxicillin-loaded carbopol-934P mucoadhesive microspheres for anti-Helicobacter pylori therapy. J Microencapsul 2011; 26:365-76. [PMID: 18720199 DOI: 10.1080/02652040802373012] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive amoxicillin microspheres for the potential use in the treatment of gastric and duodenal ulcers, which were associated with Helicobacter pylori. Amoxicillin mucoadhesive microspheres containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer were prepared by an emulsion-solvent evaporation technique. Results of preliminary trials indicate that quantity of emulsifying agent, time for stirring, drug-to-polymers ratio and speed of rotation affected the characteristics of microspheres. Microspheres were discrete, spherical, free flowing and showed a good percentage of drug entrapment efficiency. An in vitro mucoadhesive test showed that amoxicillin mucoadhesive microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X(1)) and stirring speed (X(2)) on dependent variables, i.e. percentage mucoadhesion, drug entrapment efficiency, particle size and t(80). The best batch exhibited a high drug entrapment efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle size was 109 µm. A sustained drug release was obtained for more than 12 h. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In vitro release test showed that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH 7.8 phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering amoxicillin powder and mucoadhesive microspheres to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in oral administration. The results showed that amoxicillin mucoadhesive microspheres had a better clearance effect than amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make a contribution to H. pylori complete eradication.
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Affiliation(s)
- Jayvadan K Patel
- S K Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India.
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Alazmi WM, Buhaimed W, Al-Mekhaizeem K, Siddique I. Efficacy of standard triple therapy in the treatment of Helicobacter pylori infection: experience from Kuwait. Dig Dis Sci 2010; 55:3120-3. [PMID: 20165981 DOI: 10.1007/s10620-010-1139-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2009] [Accepted: 01/26/2010] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Recent studies suggest that the initial treatment success rates for H. pylori infection are falling below 80% in many parts of the world. AIM The aim of this study was to evaluate the efficacy of standard triple therapy in the treatment of H. pylori infection in Kuwait. METHODS Consecutive H. pylori positive patients were enrolled in the study to receive clarithromycin, amoxicillin and omeprazole for 10 days. H. pylori status was checked with 13C urea breath test 6 weeks after the end of therapy. Endoscopic findings was recorded in all patients. RESULTS One hundred forty-one patients (82 male and 59 females; mean age 41.8 years) were enrolled in the study. A total of seven patients were excluded from the per protocol analysis. The eradication rates in intention to treat (ITT) and per protocol (PP) were 72.3% (95% CI 64.2-79.5%) and 76.1% (95% CI 68-83%), respectively. The main endoscopic findings were normal in 47.5% and gastritis in 37.6%. CONCLUSION The efficacy of the current standard triple therapy for H. pylori eradication in our community is suboptimal. Confirmation for H. pylori eradication with noninvasive tests is recommended, especially in high-risk patients. New antimicrobial regimens for H. pylori eradication are considered necessary.
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Affiliation(s)
- Waleed M Alazmi
- Thunayan Alghanim Center of Gastroenterology, Amiri Hospital, Kuwait City, Kuwait.
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Ramírez FB, Torres ER, Carmona JA. Criterios actuales para la erradicación de Helicobacter pylori. FMC - FORMACIÓN MÉDICA CONTINUADA EN ATENCIÓN PRIMARIA 2010; 17:158-166. [DOI: 10.1016/s1134-2072(10)70063-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Toledo H, Lopez-Solis R. Tetracycline resistance in Chilean clinical isolates of Helicobacter pylori. J Antimicrob Chemother 2009; 65:470-3. [DOI: 10.1093/jac/dkp457] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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Sharma BK, Pilania P, Sarbhai K, Singh P, Prabhakar YS. Chemometric descriptors in modeling the carbonic anhydrase inhibition activity of sulfonamide and sulfamate derivatives. Mol Divers 2009; 14:371-84. [DOI: 10.1007/s11030-009-9181-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2009] [Accepted: 07/11/2009] [Indexed: 01/19/2023]
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Cloning, polymorphism, and inhibition of beta-carbonic anhydrase of Helicobacter pylori. J Gastroenterol 2009; 43:849-57. [PMID: 19012038 DOI: 10.1007/s00535-008-2240-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2007] [Accepted: 06/26/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND Carbonic anhydrase (CA) catalyzes the reversible hydration of CO(2) to bicarbonate and a proton, and alpha-class CA has been reported to facilitate the acid acclimation of Helicobacter pylori (hpalphaCA). The purpose of this study was to characterize the beta-class CA of H. pylori (hpbetaCA) and elucidate the role of this enzyme as a possible drug target for eradication therapy. METHODS We isolated DNA clones of independent H. pylori strains obtained from patients with gastritis (n = 15), gastric ulcer (n = 6), or gastric cancer (n = 16), and then studied genetic polymorphisms. In addition, the susceptibility of H. pylori to sulpiride, an antiulcer drug and efficient inhibitor of both hpalphaCA and hpbetaCA, was studied with an in vitro killing assay. RESULTS DNA sequences of all 37 hpbetaCA clones encoded a 221 amino acid polypeptide with a variety of polymorphisms (57 types of amino acid substitution at 48 residue positions). There was no polymorphism functionally relevant to the gastric lesion type. One strain included unique residues that were not seen in the other 36 clones from Japanese patients but which were found in a strain obtained from the United Kingdom. Sulpiride had killing effects at concentrations greater than 200 microg/ml for H. pylori, including strains resistant to clarithromycin, metronidazole, or ampicillin. CONCLUSIONS Helicobacter pylori might have evolved independently in the Caucasian and Japanese populations. Dual inhibition of alpha-and beta-class CAs could be applied as alternative therapy for eradication of H. pylori.
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Kiliç ZMY, Köksal AS, Cakal B, Nadir I, Ozin YO, Kuran S, Sahin B. Moxifloxacine plus amoxicillin and ranitidine bismuth citrate or esomeprazole triple therapies for Helicobacter pylori infection. Dig Dis Sci 2008; 53:3133-7. [PMID: 18465244 DOI: 10.1007/s10620-008-0285-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2007] [Accepted: 04/09/2008] [Indexed: 12/23/2022]
Abstract
Up to 20% of patients, or even more, will fail to obtain eradication after a standard triple therapy. The aim of this study is to evaluate the efficacy of moxifloxacine-containing regimens in the first-line treatment of Helicobacter pylori. One hundred and twenty H. pylori-positive patients were randomized into four groups to receive one of the following 14-day treatments: ranitidine bismuth citrate (RBC) 400 mg b.d. plus amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (RAC group, n = 30); RBC 400 mg b.d. plus moxifloxacine 400 mg o.d. and amoxicillin 1,000 mg b.d. (RAM group, n = 30); esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus clarithromycin 500 mg b.d. (EAC group, n = 30); and esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus moxifloxacine 400 mg o.d. (EAM group, n = 30). Eradication was assessed by (13)C urea breath test 8 weeks after therapy. Per-protocol and intention-to-treat eradication was achieved in 23 out of 30 patients (76.7%, 95% confidence interval [CI]: 61-92) in the RAC group, in 20 patients (66.7%, 95% CI: 49-84) in the RAM group, in 16 patients in the EAM group (53.3%, 95% CI: 34-71), and in 19 patients in the EAC group (63.3%, 95% CI: 54-72). Mild or moderate side-effects were significantly more common in the EAM group (70%) compared to the RAC (36.6%), RAM (43.3%), and EAC (56.6%) groups (P = 0.03). From our results, we conclude that moxifloxacine-containing triple therapies have neither eradication nor compliance advantages over standard triple therapies. Further studies with new antibiotic associations are needed for the better eradication of H. pylori in developing regions of the world.
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Affiliation(s)
- Zeki Mesut Yalin Kiliç
- Department of Gastroenterology, Türkiye Yüksek Ihtisas Hospital, Sihhiye, Ankara, Turkey.
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Antibiotic resistance of Helicobacter pylori from patients in Ile-Ife, South-west, Nigeria. Afr Health Sci 2008; 7:143-7. [PMID: 18052867 DOI: 10.5555/afhs.2007.7.3.143] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori has become recognized as a major cause of gastroduodenal diseases in man. Evidence indicates that once acquired, H. pylori persists, usually for life unless eradicated by antimicrobial therapy. Over the past few years, we have accumulated some knowledge of the epidemiology of H. pylori in Ile-Ife, South-West Nigeria. In one collaborative study, we detected H. pylori in 195 (73%) patients referred for endoscopy at Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC). Furthermore we have observed a variegated gastric inflammatory response and atrophy including atrophic pangastritis but are yet to demonstrate MALToma in any of our patients. In addition we have demonstrated that dental plaque is a possible source of gastric H. pylori infection and such an endogenous source could account for difficulty in eradication leading to re-infection. Presently, infected patients are treated with standard combination therapy made up of amoxycilin and ciprofloxacin with a proton pump inhibitor/bismuth. Reports however have shown that the incidence of antimicrobial resistance in Helicobacter pylori is a growing problem and which has been linked with failures in treatment and eradication. Given this situation it has become necessary to have information about the susceptibility of isolates to particular antimicrobial agents before the selection of an appropriate treatment regimen. OBJECTIVES More recently, we sought to study antimicrobial susceptibility of locally isolated H. pylori strains. METHODS We subjected 32 isolates to antimicrobial susceptibility testing against seven agents. RESULTS All the isolates showed multiple acquired antimicrobial resistance as they were all resistant to amoxicillin, clarithromycin, metronidazole, while 29/31, 27/31 showed resistance to rifampicin and tetracycline respectively. Five (15.6%) of these isolates showed resistance to ciprofloxacin. CONCLUSIONS Our findings suggest that H. pylori strains isolated within our study environment have acquired resistance to all the commonly prescribed antibiotics. On the basis of the findings it would be necessary to re-evaluate the eradication treatment regime in our setting.
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Gisbert JP, Bermejo F, Castro-Fernández M, Pérez-Aisa A, Fernández-Bermejo M, Tomas A, Barrio J, Bory F, Almela P, Sánchez-Pobre P, Cosme A, Ortiz V, Niño P, Khorrami S, Benito LM, Carneros JA, Lamas E, Modolell I, Franco A, Ortuño J, Rodrigo L, García-Durán F, O'Callaghan E, Ponce J, Valer MP, Calvet X. Second-line rescue therapy with levofloxacin after H. pylori treatment failure: a Spanish multicenter study of 300 patients. Am J Gastroenterol 2008; 103:71-6. [PMID: 17764498 DOI: 10.1111/j.1572-0241.2007.01500.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM Quadruple therapy is generally recommended as second-line therapy after Helicobacter pylori (H. pylori) eradication failure. However, this regimen requires the administration of four drugs with a complex scheme, is associated with a relatively high incidence of adverse effects, and bismuth salts are not available worldwide anymore. Our aim was to evaluate the efficacy and tolerability of a triple second-line levofloxacin-based regimen in patients with H. pylori eradication failure. DESIGN Prospective multicenter study. PATIENTS in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin had failed. INTERVENTION A second eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. OUTCOME Eradication was confirmed with (13)C-urea breath test 4-8 wk after therapy. Compliance with therapy was determined from the interview and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS Three hundred consecutive patients were included. Mean age was 48 yr, 47% were male, 38% had peptic ulcer, and 62% functional dyspepsia. Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 81% (95% CI 77-86%) and 77% (73-82%). Adverse effects were reported in 22% of the patients, mainly including nausea (8%), metallic taste (5%), abdominal pain (3%), and myalgias (3%); none of them were severe. CONCLUSION Ten-day levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous proton pump inhibitor-clarithromycin-amoxicillin failure, being simple and safe.
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Gisbert JP, Pajares R, Pajares JM. Evolution of Helicobacter pylori therapy from a meta-analytical perspective. Helicobacter 2007; 12 Suppl 2:50-8. [PMID: 17991177 DOI: 10.1111/j.1523-5378.2007.00576.x] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Even before the discovery of Helicobacter pylori as their cause, chronic gastritis and peptic ulcer disease were empirically treated with anti-infectious agents. However, it was not until that finding that an antibiotic approach began to be used systematically. The main aim of this article is to review the evolution of H. pylori therapy from a meta-analytical perspective. Initially, antibiotic monotherapy had a minor efficacy on H. pylori. Dual therapy including either bismuth compounds or proton-pump inhibitors (PPI) and one antibiotic also resulted in insufficient cure rates. Bismuth-based triple therapy (the first used) and PPI-based triple therapies (combined with two antibiotics, including amoxicillin, nitroimidazole, or clarithromycin) have been the most widely recommended. PPI-based regimens are superior to H2-antagonist-based ones. The influence of the type of PPI, the dose and the duration of the treatment will be discussed. Among the factors influencing the efficacy of therapy, resistance to clarithromycin and metronidazole are the most important risk factors for eradication failure. Several rescue therapies can be used. Bismuth-based quadruple therapy is effective, but the complexity of the regimen and the associated adverse effects limit the compliance. PPI-based triple therapy with amoxicillin and levofloxacin is at least equally effective and better tolerated.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa, Universidad Autónoma, Madrid, Spain
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Nishimori I, Minakuchi T, Kohsaki T, Onishi S, Takeuchi H, Vullo D, Scozzafava A, Supuran CT. Carbonic anhydrase inhibitors: the beta-carbonic anhydrase from Helicobacter pylori is a new target for sulfonamide and sulfamate inhibitors. Bioorg Med Chem Lett 2007; 17:3585-94. [PMID: 17482815 DOI: 10.1016/j.bmcl.2007.04.063] [Citation(s) in RCA: 139] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2007] [Revised: 04/12/2007] [Accepted: 04/18/2007] [Indexed: 02/06/2023]
Abstract
DNA clones for the beta-class carbonic anhydrase (CA, EC 4.2.1.1) of Helicobactor pylori (hpbetaCA) were obtained. A recombinant hpbetaCA protein lacking the N-terminal 15-amino acid residues was produced and purified, representing a catalytically efficient CA. hpbetaCA was strongly inhibited (K(I)s in the range of 24-45 nM) by many sulfonamides/sulfamates, among which acetazolamide, ethoxzolamide, topiramate, and sulpiride, all clinically used drugs. The dual inhibition of alpha- and/or beta-class CAs of H. pylori might represent a useful alternative for the management of gastritis/gastric ulcers, as well as gastric cancer. This is also the first study showing that a bacterial beta-CA can be a drug target.
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Affiliation(s)
- Isao Nishimori
- Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan
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Abstract
Evaluation of: Duckworth M, Menard A, Megraud F, Mendz GL: Bioinformatic analysis of Helicobacter pylori XGPRTase: a potential therapeutic target.Helicobacter 11, 287–295 (2006). Helicobacter pylori is a globally spread pathogen, with roughly 50% of the human population being contaminated. It causes severe gastrointestinal diseases, such as chronic gastritis, peptic ulcers and gastric cancer, which lead to significant morbidity and mortality. Much effort is dedicated by scientists to design alternative strategies to treat this infection, due to the widespread emergence of resistance to the presently used pharmacological agents. The xanthine–guanine phosphoribosyltransferase (XGPRTase) enzyme of H. pylori may be one of these targets, as the enzyme was recently purified, characterized and shown to be essential to the life cycle of the parasite. Duckworth and colleagues used a bioinformatic approach to investigate this target. The parasite enzyme has been compared with those present in various bacteria, archaea and eukaryotes, and its main features have been deduced by using conserved domain analysis, multiple sequence alignment and phylognetic analysis, as well as protein 3D modeling. However, significant findings did not emerge after this work for the design of XGPRTase inhibitors.
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Affiliation(s)
- Claudiu T Supuran
- Università degli studi di Firenze, Laboratorio di Chimica Bioinorganica, Room. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy
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Gerrits MM, van Vliet AHM, Kuipers EJ, Kusters JG. Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications. THE LANCET. INFECTIOUS DISEASES 2006; 6:699-709. [PMID: 17067919 DOI: 10.1016/s1473-3099(06)70627-2] [Citation(s) in RCA: 217] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Helicobacter pylori is an important human pathogen that colonises the stomach of about half of the world's population. The bacterium has now been accepted as the causative agent of several gastroduodenal disorders, ranging from chronic active gastritis and peptic ulcer disease to gastric cancer. The recognition of H pylori as a gastric pathogen has had a substantial effect on gastroenterological practice, since many untreatable gastroduodenal disorders with uncertain cause became curable infectious diseases. Treatment of H pylori infection results in ulcer healing and can reduce the risk of gastric cancer development. Although H pylori is susceptible to many antibiotics in vitro, only a few antibiotics can be used in vivo to cure the infection. The frequent indication for anti-H pylori therapy, together with the limited choice of antibiotics, has resulted in the development of antibiotic resistance in H pylori, which substantially impairs the treatment of H pylori-associated disorders. Antimicrobial resistance in H pylori is widespread, and although the prevalence of antimicrobial resistance shows regional variation per antibiotic, it can be as high as 95%. We focus on the treatment of H pylori infection and on the clinical relevance, mechanisms, and diagnosis of antimicrobial resistance.
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Affiliation(s)
- Monique M Gerrits
- Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands
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Cheon JH, Kim SG, Kim JM, Kim N, Lee DH, Kim JS, Jung HC, Song IS. Combinations containing amoxicillin-clavulanate and tetracycline are inappropriate for Helicobacter pylori eradication despite high in vitro susceptibility. J Gastroenterol Hepatol 2006; 21:1590-5. [PMID: 16928222 DOI: 10.1111/j.1440-1746.2006.04291.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The purpose of the present paper was to evaluate the efficacy and tolerability of amoxicillin-clavulanate and tetracycline-based quadruple therapy as an alternative second-line treatment for H. pylori infection. METHODS The study subjects consisted of 54 patients infected with H. pylori, in whom initial triple therapy had failed. Subjects were randomized to receive the following 7-day therapies: (i) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., amoxicillin-clavulanate 1000 mg b.i.d., and tetracycline 500 mg q.i.d. (PBAT); or (ii) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. (PBMT). Eradication rates based on antibiotic susceptibility, drug compliance and side-effect rates were evaluated and compared. RESULTS The H. pylori eradication rates were 16.0%/17.4% with PBAT and 65.5%/70.4% with PBMT by intention-to-treat (P<0.001) and per-protocol analyses (P<0.001), respectively. In patients who received PBAT, the eradication rates were only 16.7% (2/12) for both amoxicillin and tetracycline-susceptible H. pylori strains. Drug compliance and side-effect rates were similar in the two groups. CONCLUSIONS Despite high individual in vitro antimicrobial activity, amoxicillin-clavulanate and tetracycline-based quadruple therapy showed low eradication rates, which strongly suggests that it should not be considered as a therapeutic option for H. pylori eradication.
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Affiliation(s)
- Jae Hee Cheon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Korea
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Gisbert JP, Castro-Fernández M, Bermejo F, Pérez-Aisa A, Ducons J, Fernández-Bermejo M, Bory F, Cosme A, Benito LM, López-Rivas L, Lamas E, Pabón M, Olivares D. Third-line rescue therapy with levofloxacin after two H. pylori treatment failures. Am J Gastroenterol 2006; 101:243-7. [PMID: 16454825 DOI: 10.1111/j.1572-0241.2006.00457.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin fails in a considerable number of cases. A rescue therapy still fails in more than 20% of the cases. Our aim was to evaluate the efficacy and tolerability of a third-line levofloxacin-based regimen in patients with two consecutive Helicobacter pylori eradication failures. DESIGN Prospective multicenter study. PATIENTS In whom a first treatment with omeprazole-clarithromycin-amoxicillin and a second with omeprazole-bismuth-tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed. INTERVENTION A third eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. OUTCOME Eradication was confirmed with 13C-urea breath test 4-8 wk after therapy. RESULTS One-hundred patients were initially included, and nine were lost for follow-up. All patients but five took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 66% (95% CI = 56-75%) and 60% (50-70%). Adverse effects were reported in 25% of the patients, mainly including metallic taste (8%), nausea (8%), myalgia/arthralgia (5%), and diarrhea (4%); none of them were severe. CONCLUSION Levofloxacin-based rescue therapy constitutes an encouraging empirical third-line strategy after multiple previous H. pylori eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, and tetracycline.
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Cheon JH, Kim N, Lee DH, Kim JM, Kim JS, Jung HC, Song IS. Efficacy of moxifloxacin-based triple therapy as second-line treatment for Helicobacter pylori infection. Helicobacter 2006; 11:46-51. [PMID: 16423089 DOI: 10.1111/j.0083-8703.2006.00371.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Metronidazole and tetracycline-based second-line quadruple therapy, widely used for Helicobacter pylori infection, often ends up in failure due to antibiotic resistance and poor compliance in Korea. Our aim is to evaluate the efficacy and tolerability of moxifloxacin-based triple therapy as an alternative second-line treatment for H. pylori infection. METHODS The subjects consisted of 85 patients infected with H. pylori, in whom initial proton pump inhibitor triple therapy had failed. They were randomized to receive the following 7-day therapy: 1, moxifloxacin 400 mg q.d., esomeprazole 20 mg b.i.d., and amoxicillin 1 g b.i.d.; and 2, esomeprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. Eradication rates, drug compliance, and side-effect rates of each group were evaluated. RESULTS The eradication rates were 75.6 and 83.8% with moxifloxacin triple therapy, and 54.5 and 72.7% with quadruple therapy by intention-to-treat (p = .042) and per-protocol analyses (p = .260), respectively. Moxifloxacin triple therapy was significantly superior to quadruple therapy in terms of side-effect rates (p = .039). Compliance for therapy, i.e., the percentage of tablets taken (> 85%), was 90.2 and 75.0%, numerically higher in moxifloxacin triple therapy group than in quadruple therapy group, but without statistical difference (p = .065). CONCLUSIONS Moxifloxacin-based triple therapy showed high eradication rates with few side effects and good drug compliance, suggesting this regimen could be a safe and effective option as second-line therapy for H. pylori infection in Korea.
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Affiliation(s)
- Jae Hee Cheon
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Matsushima M, Suzuki T, Kurumada T, Watanabe S, Watanabe K, Kobayashi K, Deguchi R, Masui A, Takagi A, Shirai T, Muraoka H, Kobayashi I, Mine T. Tetracycline, metronidazole and amoxicillin-metronidazole combinations in proton pump inhibitor-based triple therapies are equally effective as alternative therapies against Helicobacter pylori infection. J Gastroenterol Hepatol 2006; 21:232-6. [PMID: 16460479 DOI: 10.1111/j.1440-1746.2006.04171.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND A proton pump inhibitor (PPI)-based triple therapy with clarithromycin (CAM) and amoxicillin (AMPC) is now a standard regimen for Helicobacter pylori (HP) eradication in Japan. However, the CAM-resistant rate has increased recently and alternative therapies are sorely needed. Therefore the aim of the present study was to evaluate the effectiveness and safety of the PPI-tetracycline (TC)-metronidazole (MNZ) regimen (the PTM regimen) as an alternative therapy in comparison with the PPI-AMPC-MNZ (PAM) regimen. METHODS Sixty-four HP-positive patients visiting the HP-eradication clinic in Tokai University Hospital from July 1998 to March 2003 were treated with either PTM or PAM as alternative therapies. The HP eradication was assessed by urea breath test (UBT), HP stool antigen test, or HP culture method more than 2 months after completion of the treatments. The drug resistances against CAM, AMPC, TC, and MNZ were assessed by the agar dilution method. RESULTS Fifty-six patients (26 PTM and 30 PAM) completed medication and evaluation of the eradication. The eradication rates of PTM were 82.8% (24/29) and 92.3% (24/26), while those of PAM were 74.3% (26/35) and 89.7% (26/29) by intention-to-treat and per-protocol analysis, respectively. The differences between the regimens were not statistically significant. There were no severe adverse effects observed in either of the regimens. The drug-resistance analyses showed 15 CAM- and one MNZ-resistant cases but no TC or AMPC resistance in the available 25 samples. CONCLUSION The PTM and PAM regimens were equally effective and safe as alternative HP eradication therapies. And PTM would be particularly useful in penicillin allergy cases.
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Affiliation(s)
- Masashi Matsushima
- Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
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Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 2006; 23:35-44. [PMID: 16393278 DOI: 10.1111/j.1365-2036.2006.02737.x] [Citation(s) in RCA: 193] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND A quadruple therapy has been generally recommended as rescue regimen for Helicobacter pylori eradication failures. AIMS To systematically review the efficacy and tolerance of levofloxacin-based rescue regimens, and to conduct a meta-analysis of studies comparing these regimens with quadruple therapy for H. pylori eradication failures. METHODS Selection of studies -- levofloxacin-based rescue regimens. For the meta-analysis, randomized-controlled trials comparing levofloxacin-based and quadruple regimens. Search strategy -- electronic and manual. Assessment of study quality -- independently by two reviewers. Data synthesis --'intention-to-treat' eradication rate. RESULTS Mean eradication rate with levofloxacin-based regimens was 80%. Ten-day regimens were more effective than 7-day combinations (81% vs. 73%; P < 0.01). The meta-analysis showed better results with levofloxacin than with the quadruple combination (81% vs. 70%; OR = 1.80; 95% CI = 0.94-3.46). This difference reached statistical significance and heterogeneity markedly decreased when a single outlier study was excluded or when only high-quality studies were considered. Meta-analysis showed less adverse effects with levofloxacin than with quadruple regimen, both overall (19% vs. 44%; OR = 0.27; 95% CI = 0.16-0.46) and regarding severe adverse effects (0.8% vs. 8.4%; OR = 0.20; 95% CI =0.06-0.67). CONCLUSIONS After H. pylori eradication failure, levofloxacin-based rescue regimen is more effective and better tolerated than the generally recommended quadruple therapy. A 10-day combination of levofloxacin-amoxicillin-proton pump inhibitor constitutes an encouraging second-line alternative.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital of 'La Princesa', Madrid, Spain.
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Abstract
AIM: To examine the frequency of antibiotic resistance in Iranian Helicobacter pylori (H pylori) strains isolated from two major hospitals in Tehran.
METHODS: Examination of antibiotic resistance was performed on 120 strains by modified disc diffusion test and PCR-RFLP methods. In addition, in order to identify the possible causes of the therapeutic failure in Iran, we also determined the resistance of these strains to the most commonly used antibiotics (metronidazole, amoxicillin, and tetracycline) by modified disc diffusion test.
RESULTS: According to modified disc diffusion test, 1.6% of the studied strains were resistant to amoxicillin, 16.7% to clarithromycin, 57.5% to metronidazole, and there was no resistance to tetracycline. Of the clarithromycin resistant strains, 73.68% had the A2143G mutation in the 23S rRNA gene, 21.05% A2142C, and 5.26% A2142G. None of the sensitive strains were positive for any of the three point mutations. Of the metronidazole resistant strains, deletion in rdxA gene was studied and detected in only 6 (5%) of the antibiogram-based resistant strains. None of the metronidazole sensitive strains possessed rdxAgene deletion.
CONCLUSION: These data show that despite the fact that clarithromycin has not yet been introduced to the Iranian drug market as a generic drug, nearly 20% rate of resistance alerts toward the frequency of macrolide resistance strains, which may be due to the widespread prescription of erythromycin in Iran. rdxA gene inactivation, if present in Iranian H pylori strains, may be due to other genetic defects rather than gene deletion.
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Affiliation(s)
- Marjan Mohammadi
- Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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27
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Abstract
Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face Helicobacter pylori treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final--overall--eradication rate. After failure of a combination of proton pump inhibitor (PPI), amoxicillin, and clarithromycin, the use of empirical quadruple therapy (PPI-bismuth-tetracycline-metronidazole), has been generally used as the optimal second-line therapy. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several "rescue" therapies are consecutively given. It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximize H. pylori eradication, based on the different possibilities of empirical treatment (when antibiotic susceptibilities are unknown). Thus, if one does not want to perform culture before the administration of the third treatment after failure of the first two, different empirical treatments exist, including regimens based on: 1, amoxicillin (amoxicillin-PPI at high doses); 2, amoxicillin plus tetracycline (PPI-bismuth-tetracycline-amoxicillin, or ranitidine-bismuth-citrate-tetracyline-amoxicillin); 3, rifabutin (rifabutin-amoxicillin-PPI); 4, levofloxacin (levofloxacin-amoxicillin-PPI); and 5, furazolidone (furazolidone-bismuth-tetracycline-PPI).
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Affiliation(s)
- Javier P Gisbert
- Department of Gastroenterology, University Hospital of La Princesa, Madrid, Spain.
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Glocker E, Berning M, Gerrits MM, Kusters JG, Kist M. Real-time PCR screening for 16S rRNA mutations associated with resistance to tetracycline in Helicobacter pylori. Antimicrob Agents Chemother 2005; 49:3166-70. [PMID: 16048919 PMCID: PMC1196286 DOI: 10.1128/aac.49.8.3166-3170.2005] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The effectiveness of recommended first-line therapies for Helicobacter pylori infections is decreasing due to the occurrence of resistance to metronidazole and/or clarithromycin. Quadruple therapies, which include tetracycline and a bismuth salt, are useful alternative regimens. However, resistance to tetracycline, mainly caused by mutations in the 16S rRNA genes (rrnA and rrnB) affecting nucleotides 926 to 928, are already emerging and can impair the efficacies of such second-line regimens. Here, we describe a novel real-time PCR for the detection of 16S rRNA gene mutations associated with tetracycline resistance. Our PCR method was able to distinguish between wild-type strains and resistant strains exhibiting single-, double, or triple-base-pair mutations. The method was applicable both to DNA extracted from pure cultures and to DNA extracted from fresh or frozen H. pylori-infected gastric biopsy samples. We therefore conclude that this real-time PCR is an excellent method for determination of H. pylori tetracycline resistance even when live bacteria are no longer available.
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Affiliation(s)
- Erik Glocker
- Nationales Referenzzentrum für Helicobacter pylori, Abteilung Medizinische Mikrobiologie und Hygiene, Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany
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Dai G, Cheng N, Dong L, Muramatsu M, Xiao S, Wang MW, Zhu DX. Bactericidal and morphological effects of NE-2001, a novel synthetic agent directed against Helicobacter pylori. Antimicrob Agents Chemother 2005; 49:3468-73. [PMID: 16048962 PMCID: PMC1196265 DOI: 10.1128/aac.49.8.3468-3473.2005] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The antibacterial activities of NE-2001 were tested against 24 clinical isolates of Helicobacter pylori and compared with those of amoxicillin, clarithromycin, metronidazole, and furazolidone. The MIC(50) and MIC(90) of this synthetic compound on the isolates were 8 and 16 mug/ml, respectively. This action was highly selective against Helicobacter pylori; there was a >4-fold difference between the concentration of NE-2001 required to inhibit the growth of Helicobacter pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of Helicobacter pylori (ATCC43504) to NE-2001 at the MIC (4 mug/ml), or at a greater concentration, resulted in an extensive loss of viability. The phenomenon was also observed at pH levels between 3.0 and 7.0. When two clinical Helicobacter pylori strains were successively cultured at subinhibitory concentrations of NE-2001, no significant changes in the bactericidal effects were found. The morphological alterations of Helicobacter pylori cells (ATCC43504), exposed to NE-2001 at various concentrations for 6 h, were observed using transmission electron microcopy. The bacterium displayed features such as swelling, vacuole-like structures in the cytoplasm, and cell destruction following exposure to NE-2001. The efficacy of NE-2001 was maintained when evaluated in eight clinical isolates resistant to metronidazole and five isolates resistant to both metronidazole and clarithromycin (MIC ranging between 4 and 16 mug/ml). The above-described results suggest that NE-2001 may have the potential to be developed as a candidate agent for the treatment of Helicobacter pylori infection.
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Affiliation(s)
- Guofei Dai
- Department of Biochemistry, Nanjing University, Nanjing 210093, P.R. China
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Gisbert JP, Calvet X, Gomollón F, Monés J. Tratamiento erradicador de Helicobacter pylori. Recomendaciones de la II Conferencia Española de Consenso. Med Clin (Barc) 2005; 125:301-16. [PMID: 16159556 DOI: 10.1157/13078424] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Madrid, Spain.
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Köksal AS, Parlak E, Filik L, Yolcu OF, Odemiş B, Ulker A, Saşmaz N, Ozden A, Sahin B. Ranitidine bismuth citrate-based triple therapies as a second-line therapy for Helicobacter pylori in Turkish patients. J Gastroenterol Hepatol 2005; 20:637-42. [PMID: 15836716 DOI: 10.1111/j.1440-1746.2005.03801.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline is recommended as the optimal second-line therapy of Helicobacter pylori infection in the Maastricht Consensus Report. The aim of the present paper was to evaluate the efficacy of ranitidine bismuth citrate (RBC)-based regimens as second-line therapies after failure of the standard Maastricht triple therapy. MATERIALS AND METHODS One hundred and sixteen H. pylori-positive patients were given omeprazole 20 mg b.d., clarithromycin 500 mg b.d., and amoxicillin 1 g b.d for 10 days. Patients remaining H. pylori-positive (n = 29) were combined with 27 patients enrolled after an initial eradication failure from proton-pump inhibitor (PPI), amoxicillin and clarithromycin therapy for at least 7 days and were randomly given one of the following second-line 10-day treatments: RBC 400 mg b.d., amoxicillin 1 g b.d and clarithromycin 500 mg b.d. (RAC group, n = 28) and RBC 400 mg b.d., metronidazole 500 mg b.d and tetracycline 500 mg b.d. (RMT group, n = 28). Eradication was assessed by either histology and rapid urease test or (13)C urea breath test 8 weeks after therapy. RESULTS The eradication rate of first-line Maastricht therapy was 67% for intention-to-treat analysis (95% confidence interval [CI]: 58-75). Per-protocol and intention-to-treat eradication was achieved in 60.7% of patients (95%CI: 42-79) in the RAC group and in 85.7% of patients (95%CI: 73-98) in the RMT group (P = 0.03). Fifty-three percent of patients in the RAC and 50% of patients in the RMT group experienced at least one slight side-effect (P = 0.6). CONCLUSIONS RMT is an effective and well-tolerated second-line therapy after H. pylori eradication failure from PPI, amoxicillin, and clarithromycin.
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Affiliation(s)
- Aydin S Köksal
- Department of Gastroenterology, Türkiye Yüksek Ihtisas Hospital, Ankara, Turkey.
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Toracchio S, Capodicasa S, Soraja DB, Cellini L, Marzio L. Rifabutin based triple therapy for eradication of H. pylori primary and secondary resistant to tinidazole and clarithromycin. Dig Liver Dis 2005; 37:33-8. [PMID: 15702857 DOI: 10.1016/j.dld.2004.09.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Rifabutin has been empirically used in Helicobacter pylori infections resistant to triple therapy. There are no data on primary and secondary resistance to rifabutin and its use in specific cases. AIM To analyse the susceptibility and resistance to rifabutin in H. pylori-positive patients with or without previous H. pylori therapy and to test the efficacy of rifabutin in H. pylori resistant to clarithromycin and tinidazole. METHODS Four hundred and twenty H. pylori-positive patients without previous exposure to triple therapy and 104 patients who had already received one course of triple therapy underwent upper endoscopy for dyspeptic symptoms and H. pylori susceptibility test. Amoxicillin, clarithromycin, tinidazole and rifabutin were evaluated for resistance and susceptibility. Forty patients with primary resistance to both clarithromycin and tinidazole and with susceptibility to amoxicillin and rifabutin, and 65 patients with secondary resistance and susceptibility to the same antibiotics were identified. All these patients received a 10-day triple therapy with pantoprazole amoxicillin and rifabutin. Treatment success was evaluated by the 13C-Urea Breath test. RESULTS In naive patients 23% of strains were resistant to clarythromycin, 35% to tinidazole, 9% to both antibiotics, and none was resistant to rifabutin In patients already treated the percentages of resistant strains were 76, 64.4, 62.5 and 1%, respectively. With rifabutin based triple therapy eradication rates were (Per Protocol and Intention-to-Treat analysis) 100 and 87.5% in primary resistance to clarithromycin and tinidazole and 82.2 and 78.5% in secondary resistance. CONCLUSION H. pylori primary and secondary resistances to clarithromycin and tinidazole are high in our geographic area, while resistance to rifabutin is rare. Rifabutin-based triple therapy, can be successfully used in primary and secondary resistance to clarithromycin and tinidazole according to the in vitro susceptibility test.
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Affiliation(s)
- S Toracchio
- Section of Molecular Pathology, Department of Oncology and Neuroscience, G. d'Annunzio University, Chieti-Pescara, Italy
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Abstract
At present, antisecretory drugs--foremost among them the proton pump inhibitors (PPIs)--represent a keystone in Helicobacter pylori eradication therapy. The present article shall first compare the role of PPIs as compared with histamine H2 receptor antagonists, both of them in the role of antibiotic-associated antisecretory therapy, and shall then address the contribution of each of the various PPIs that have been developed until the present time to the H. pylori eradication therapies. In summary, it may be concluded that PPIs are more effective overall than H2 receptor antagonists when the two groups of antisecretory drugs are given at the usual standard doses together with antibiotics with the intention of eradicating H. pylori infection. However, all PPIs (omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole) are equivalent when given together with two antibiotics to cure the infection.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Service, La Princesa University Hospital, Madrid, Spain.
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Elizalde JI, Pérez-Pujol S, Heras M, Sionis A, Casanovas N, Martorell T, Lozano M, González J, Escolar G, Sanz G, Piqué JM. Effects of Helicobacter pylori eradication on platelet activation and disease recurrence in patients with acute coronary syndromes. Helicobacter 2004; 9:681-9. [PMID: 15610084 DOI: 10.1111/j.1083-4389.2004.00271.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Platelet activation is consistently observed in animal models of Helicobacter pylori infection and could help to explain the alleged epidemiological association between H. pylori and coronary heart disease. MATERIALS AND METHODS Ninety-two patients with recent acute coronary syndromes were enrolled. Helicobacter pylori-positive patients were randomized to receive a 7-day course of omeprazole, amoxycillin and metronidazole or placebos. Two months later, H. pylori status was reassessed and baseline parameters, including soluble P-selectin and platelet surface expression of CD62P, CD63 and CD41, were measured again. Patients were followed-up for 1 year or until death or readmission. RESULTS No baseline differences were observed between H. pylori-positive and -negative cases. Among H. pylori-positive patients, 18 received placebo and 31 received active medication resulting in eradication in 21 cases. No differences were observed in inflammatory parameters or platelet activation markers between patients with persistent or resolved H. pylori infection. However, coronary events recurred at 6 and 12 months, respectively, in 35% and 55% of patients with persisting H. pylori infection compared with 10% and 25% of patients in whom H. pylori was either absent or eradicated (p = .01). Only final H. pylori status [RR 3.07 (95% CI 1.35-98)] and number of coronary risk factors [RR 2.58 (95% CI 1.51-4.41)] were independent predictors of recurrence. CONCLUSIONS Infection with H. pylori does not induce significant platelet activation in patients treated for coronary disease. Helicobacter pylori-infected patients, however, may have an increased risk of recurrence of coronary events.
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Affiliation(s)
- J Ignasi Elizalde
- Gastroenterology Department, Institut Clínic de Malalties Digestives, University of Barcelona, Barcelona, Spain
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Turi S, Schilling D, Riemann JF. [Eradication and chronic acid suppression. Advances and pseudo-advances]. Internist (Berl) 2004; 45:1305-14. [PMID: 15232691 DOI: 10.1007/s00108-004-1237-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Guidelines for Helicobacter pylori therapy were proposed at the Maastricht 2/2000 conference. Since then no further major developments have been made. An evidenced based choice of treatment is thereby nearly impossible as large randomized trials have not been performed. Minor progress could be achieved in the areas of second-line and rescue treatment options after failure of the standard therapy. At present proton pump inhibitors are the most powerful drugs for the treatment of gastro-oesophageal reflux disease. No additional progress has been achieved concerning therapy of reflux disease in the last years. Reasonable anxiety about the safety of long-term acid suppression with proton pump inhibitors diminished over years as no significant increase in cancer development could be detected.
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Affiliation(s)
- S Turi
- Medizinische Klinik C, Klinikum der Stadt Ludwigshafen gGmbH.
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36
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Abstract
AIM To perform a systematic review on the efficacy of esomeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of esomeprazole and other proton pump inhibitors when co-prescribed with antibiotics. METHODS Studies evaluating esomeprazole plus antibiotics were considered. Only randomised trials comparing esomeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographical searches were conducted. The percentage (weighted mean) of eradication success was calculated. Meta-analysis was performed combining the odd ratios of the individual studies. RESULTS Mean cure rates with dual regimens (esomeprazole plus clarithromycin) were 51 and 54%, respectively, by intention-to-treat and by per-protocol. Corresponding figures with triple regimens (esomeprazole plus clarithromycin and either amoxicillin or metronidazole) were 82% (intention-to-treat) and 86% (per-protocol). Four studies were included in the meta-analysis: mean H. pylori eradication rates (intention-to-treat) with esomeprazole plus antibiotics was 85 and 82% when omeprazole was used (odds ratio = 1.19; 95% confidence interval = 0.81-1.74), results being statistically homogeneous. When subanalysis included only high quality studies, the odds ratio for this comparison was closer to one (1.08; 95% confidence interval = 0.4-1.47) and results were more homogeneous. CONCLUSIONS Esomeprazole-based triple therapy is highly effective for the eradication of H. pylori infection and offers comparable efficacy to omeprazole-based therapy.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital of "la Princesa", Playa de Mojácar 29. Urb. Bonanza, 28669 Boadilla del Monte, Madrid, Spain.
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37
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Ribeiro ML, Gerrits MM, Benvengo YHB, Berning M, Godoy APO, Kuipers EJ, Mendonça S, van Vliet AHM, Pedrazzoli J, Kusters JG. Detection of high-level tetracycline resistance in clinical isolates of Helicobacter pylori using PCR-RFLP. ACTA ACUST UNITED AC 2004; 40:57-61. [PMID: 14734187 DOI: 10.1016/s0928-8244(03)00277-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Tetracycline is one of four antibiotics commonly used for the treatment of Helicobacter pylori infection, but its effectiveness is decreasing as the incidence of tetracycline resistance is increasing. In five Brazilian tetracycline-resistant (Tet(R)) H. pylori isolates, high-level tetracycline resistance is mediated by the triple-base-pair substitution AGA(926-928)-->TTC in both 16S rRNA genes, as was previously observed in two independent high-level Tet(R) H. pylori strains. A polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) assay was developed for the detection of the AGA(926-928)-->TTC substitution, and confirmed the presence of the aforementioned triple-base-pair substitution in all five Brazilian Tet(R) isolates. This PCR-RFLP-based approach distinguishes the high-level Tet(R) isolates from low-level Tet(R) and Tet(S) H. pylori strains and thus allows the direct detection of Tet(R) H. pylori isolates.
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Affiliation(s)
- Marcelo L Ribeiro
- Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP, Brazil
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38
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Gisbert JP, Gisbert JL, Marcos S, Pajares JM. Empirical Helicobacter pylori "rescue" therapy after failure of two eradication treatments. Dig Liver Dis 2004; 36:7-12. [PMID: 14971810 DOI: 10.1016/j.dld.2003.09.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM Even with the current most effective Helicobacter pylori treatment regimens, approximately 20% of patients do not eradicate the infection. Several "rescue" therapies have been recommended, but they still fail to eradicate H. pylori in approximately 20-30% of the cases. Our aim was to evaluate the efficacy of different rescue therapies prescribed to patients in whom two consecutive H. pylori eradication regimens had failed. METHODS Design. Prospective single-centre study. Patients. Consecutive patients in whom two eradication regimens had failed to eradicate H. pylori. Intervention. Third eradication regimens included: (1) omeprazole-amoxicillin-clarithromycin for 7 days; (2) quadruple therapy with omeprazole-bismuth-tetracycline-metronidazole for 7 days; (3) omeprazole-amoxicillin-clarithromycin-bismuth for 14 days; and (4) omeprazole-amoxicillin-rifabutin for 14 days. H. pylori antibiotic susceptibility was unknown and, therefore, rescue regimens were chosen empirically. In no case, was the same regimen repeated. Outcome. H. pylori eradication was defined as a negative in 13C-urea breath test 8 weeks after completing the therapy. RESULTS Forty-eight patients were included (mean age 45 years, 44% males, 82% with peptic ulcer and 18% with functional dyspepsia). No patient was lost from follow-up. Adverse effects were described in 21% of the patients. One patient receiving omeprazole, amoxicillin and rifabutin was removed from medication due to adverse effects (vomiting). Overall, mean H. pylori eradication with third therapy after failure of two eradication treatments was 34/48 (71%; 95% confidence interval 57-82%) by intention-to-treat and 34/47 (72%; 95% confidence interval 58-83%) by per-protocol. CONCLUSION It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximise H. pylori eradication, based on the different possibilities of empirical treatment.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, La Princesa University Hospital, Madrid, Spain.
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39
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Gisbert JP, Khorrami S, Calvet X, Pajares JM. Pantoprazole based therapies in Helicobacter pylori eradication: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2004; 16:89-99. [PMID: 15095858 DOI: 10.1097/00042737-200401000-00014] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM To perform a systematic review on the efficacy of pantoprazole based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of pantoprazole and other proton pump inhibitors (PPIs) when co-prescribed with antibiotics. METHODS Studies evaluating pantoprazole combined with antibiotics were considered. Only randomized clinical trials comparing pantoprazole and other PPIs when co-prescribed with antibiotics, and differing only in the PPI (pantoprazole vs other), were eligible for inclusion in the meta-analysis. Bibliographical searches in several electronic databases, and manual search of abstracts from congresses, were conducted. The percentage (weighted mean) of patients with eradication success was calculated. Meta-analysis was performed combining the odds ratios (ORs) of the individual studies in a global OR. RESULTS The mean eradication rate with pantoprazole plus clarithromycin for 14 days was 60%. Cure rates with 7 day pantoprazole based triple regimens were higher: pantoprazole, amoxicillin and clarithromycin (78%); pantoprazole, clarithromycin and nitroimidazole (84%); and pantoprazole, amoxicillin and nitroimidazole (74%). Twelve studies comparing pantoprazole and other PPIs were selected for the meta-analysis, including 534 and 603 patients, respectively. The mean eradication rate for H. pylori using pantoprazole plus antibiotics was 83%, and 81% when other PPIs were used (OR = 1; 95% confidence interval (CI) from 0.61 to 1.64). When sub-analysis was performed, including only studies comparing pantoprazole with omeprazole, or pantoprazole with lansoprazole, differences were also statistically non-significant. The meta-analysis of the six studies prescribing equivalent doses of all PPIs demonstrated similar results with pantoprazole and with other PPIs (OR = 1.07; 95% CI from 0.71 to 1.62), the results being statistically homogeneous. CONCLUSIONS Pantoprazole achieves similar cure rates to those of omeprazole and lansoprazole when co-prescribed with antibiotics for the eradication of H. pylori infection.
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Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Madrid, Spain.
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40
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Gisbert JP, Khorrami S, Calvet X, Gabriel R, Carballo F, Pajares JM. Meta-analysis: proton pump inhibitors vs. H2-receptor antagonists--their efficacy with antibiotics in Helicobacter pylori eradication. Aliment Pharmacol Ther 2003; 18:757-66. [PMID: 14535868 DOI: 10.1046/j.1365-2036.2003.01766.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND It is unknown whether proton pump inhibitors are superior to H2-receptor antagonists in Helicobacter pylori eradication regimens. AIM To perform a meta-analysis comparing the efficacy of both antisecretors when co-prescribed with antibiotics. METHODS Randomized clinical trials comparing proton pump inhibitors vs. H2-receptor antagonists with the same antibiotics were selected. Data sources included PubMed, the Cochrane Controlled Trials Register and abstracts from congresses up to January 2002. A meta-analysis was performed by combining the odds ratios. RESULTS Twenty studies fulfilled the inclusion criteria. In the intention-to-treat analysis, the mean eradication rates with proton pump inhibitors and H2-receptor antagonists plus antibiotics were 74% [95% confidence interval (CI), 71-76%] and 69% (95% CI, 66-71%), respectively. The odds ratio for this comparison was 1.31 (95% CI, 1.09-1.58). The number needed to treat with proton pump inhibitors to achieve eradication success, compared with H2-receptor antagonists, was 25. When studies prescribing very high doses of H2-receptor antagonists (two of the outliers) were excluded, the odds ratio (for proton pump inhibitors vs. H2-receptor antagonists) increased to 1.37, the number needed to treat decreased to 20 and the heterogeneity between the studies decreased. CONCLUSIONS Overall, proton pump inhibitors are more effective than H2-receptor antagonists when prescribed at usual doses with antibiotics to eradicate H. pylori infection.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital, Madrid, Spain.
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41
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Gisbert JP, Calvet X, Bujanda L, Marcos S, Gisbert JL, Pajares JM. 'Rescue' therapy with rifabutin after multiple Helicobacter pylori treatment failures. Helicobacter 2003; 8:90-4. [PMID: 12662375 DOI: 10.1046/j.1523-5378.2003.00128.x] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
AIM Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin is extensively used, although it fails in a considerable number of cases. A 'rescue' therapy with a quadruple combination of omeprazole, bismuth, tetracycline and metronidazole (or ranitidine bismuth citrate with these same antibiotics) has been recommended, but it still fails in approximately 20% of cases. Our aim was to evaluate the efficacy and tolerability of a rifabutin-based regimen in patients with two consecutive H. pylori eradication failures. PATIENTS AND METHODS DESIGN Prospective multicenter study. PATIENTS Consecutive patients in whom a first eradication trial with omeprazole, clarithromycin and amoxicillin and a second trial with omeprazole, bismuth, tetracycline and metronidazole (three patients) or ranitidine bismuth citrate with these same antibiotics (11 patients) had failed were included. INTERVENTION A third eradication regimen with rifabutin (150 mg bid), amoxicillin (1 g bid) and omeprazole (20 mg bid) was prescribed for 14 days. All drugs were administered together after breakfast and dinner. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. OUTCOME H. pylori eradication was defined as a negative 13C-urea breath test 8 weeks after completing therapy. RESULTS Fourteen patients have been included. Mean age +/- SD was 42 +/- 11 years, 41% males, peptic ulcer (57%), functional dyspepsia (43%). All patients took all the medications and completed the study protocol. Per-protocol and intention-to-treat eradication was achieved in 11/14 patients (79%; 95% confidence interval = 49-95%). Adverse effects were reported in five patients (36%), and included: abdominal pain (three patients), nausea and vomiting (one patient), and oral candidiasis (one patient); no patient abandoned the treatment due to adverse effects. CONCLUSION Rifabutin-based rescue therapy constitutes an encouraging strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline.
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Affiliation(s)
- Javier P Gisbert
- Department of Gastroenterology, La Princesa University Hospital, Madrid, Spain
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42
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Gisbert JP, Pajares JM. Treatment of Helicobacter pylori Eradication Failures. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2003; 6:147-156. [PMID: 12628073 DOI: 10.1007/s11938-003-0015-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Even with the current most effective treatment regimens, about 10% to 20% of patients will fail to eradicate Helicobacter pylori infection. Therefore, in designing a treatment strategy, we should not focus on the results of primary therapy alone but also on the final (overall) eradication rate. The choice of a second-line treatment depends on which treatment was used initially, because retreatment with the same regimen is not recommended. Therefore, it seems that performing culture after a first eradication failure is not necessary and assessing H. pylori sensitivity to antibiotics only after failure of the second treatment is suggested in clinical practice. Different possibilities of empirical treatment are suggested. After failure of proton pump inhibitor (PPI)-amoxicillin-clarithromycin, quadruple therapy has been generally used. More recently, replacing the PPI and the bismuth compound by ranitidine bismuth citrate has also achieved good results. After PPI-amoxicillin-nitroimidazole failure, retreatment with PPI-amoxicillin-clarithromycin has proved to be effective. Finally, the first therapy should not combine clarithromycin and metronidazole in the same regimen because of the problem of resistance against both antibiotics. Recently, rifabutin-based rescue therapies have been shown to constitute an encouraging strategy for eradication failures because they are effective for H. pylori strains resistant to antibiotics.
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Affiliation(s)
- Javier P. Gisbert
- Gastroenterology Unit, La Princesa University Hospital, Playa de Mojácar 29, 28669 Boadilla del Monte, Madrid, Spain.
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Gisbert JP, Khorrami S, Calvet X, Pajares JM. Systematic review: Rabeprazole-based therapies in Helicobacter pylori eradication. Aliment Pharmacol Ther 2003; 17:751-64. [PMID: 12641497 DOI: 10.1046/j.1365-2036.2003.01450.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co-prescribed with antibiotics. METHODS Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta-analysis was performed by combining the odds ratios (OR) of the individual studies. RESULTS The eradication rates were as follows: 14-day rabeprazole-amoxicillin, 73%; rabeprazole-amoxicillin-clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low-dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high-dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7-day rabeprazole-clarithromycin-nitroimidazole, 85%. Twelve comparative studies were included in the meta-analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93-1.42). Sub-analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences. CONCLUSIONS Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co-prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection.
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Affiliation(s)
- J P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Madrid, Spain.
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Leong RWL, Lee CC, Ling TKW, Leung WK, Sung JJY. Evaluation of the string test for the detection of Helicobacter pylori. World J Gastroenterol 2003; 9:309-11. [PMID: 12532455 PMCID: PMC4611335 DOI: 10.3748/wjg.v9.i2.309] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Helicobacter pylori can be diagnosed by invasive or non-invasive tests but to obtain bacteria for culture and antibiotic susceptibility testing, an upper GI endoscopy is often required. The string test may be a minimally-invasive alternative method of obtaining H. pylori samples. This study evaluates the sensitivity and specificity of the string test in the diagnosis of H. pylori in comparison with endoscopic means of diagnosis.
METHODS: This was a prospective open comparative study of patients with dyspepsia with endoscopy-based tests as gold standard (defined as a positive CLO test and antral histology). Fasting patients swallowed the encapsulated-string (Entero-test Hp), which was withdrawn after 1 h. The gastric juice from the string was plated onto H. pylori-selective media for culture. Helicobacter pylori was identified by typical colony morphology, gram stain and biochemical test results.
RESULTS: Thirty dyspeptic patients were recruited of whom 21 (70%) were positive for H. pylori according to the gold standard. The sensitivity, specificity, positive predictive value, and negative predictive value for the string test were 38%, 100%, 100% and 41% respectively, and for endoscopic biopsies 81%, 100%, 100%, 69% respectively (P = 0.004). Logistic regression showed that only abundant growth density from endoscopic biopsy cultures to be a predictor of a positive string test (P = 0.018).
CONCLUSION: The string test is an alternative method to endoscopy in obtaining H. pylori but has a low sensitivity compared to endoscopic biopsies.
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Affiliation(s)
- Rupert W L Leong
- Department of Gastroenterology, University of New South Wales, Bankstown Hospital, Sydney, Australia
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45
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Dailidiene D, Bertoli MT, Miciuleviciene J, Mukhopadhyay AK, Dailide G, Pascasio MA, Kupcinskas L, Berg DE. Emergence of tetracycline resistance in Helicobacter pylori: multiple mutational changes in 16S ribosomal DNA and other genetic loci. Antimicrob Agents Chemother 2002; 46:3940-6. [PMID: 12435699 PMCID: PMC132778 DOI: 10.1128/aac.46.12.3940-3946.2002] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Tetracycline is useful in combination therapies against the gastric pathogen Helicobacter pylori. We found 6 tetracycline-resistant (Tet(r)) strains among 159 clinical isolates (from El Salvador, Lithuania, and India) and obtained the following four results: (i) 5 of 6 Tet(r) isolates contained one or two nucleotide substitutions in one part of the primary tetracycline binding site in 16S rRNA (AGA(965-967) [Escherichia coli coordinates] changed to gGA, AGc, guA, or gGc [lowercase letters are used to represent the base changes]), whereas the sixth (isolate Ind75) retained AGA(965-967); (ii) PCR products containing mutant 16S ribosomal DNA (rDNA) alleles transformed recipient strains to Tet(r) phenotypes, but transformants containing alleles with single substitutions (gGA and AGc) were less resistant than their Tet(r) parents; (iii) each of 10 Tet(r) mutants of reference strain 26695 (in which mutations were induced with metronidazole, a mutagenic anti-H. pylori agent) contained the normal AGA(965-967) sequence; and (iv) transformant derivatives of Ind75 and of one of the Tet(r) 26695 mutants that had acquired mutant rDNA alleles were resistant to tetracycline at levels higher than those to which either parent strain was resistant. Thus, tetracycline resistance in H. pylori results from an accumulation of changes that may affect tetracycline-ribosome affinity and/or other functions (perhaps porins or efflux pumps). We suggest that the rarity of tetracycline resistance among clinical isolates reflects this need for multiple mutations and perhaps also the deleterious effects of such mutations on fitness. Formally equivalent mutations with small but additive effects are postulated to contribute importantly to traits such as host specificity and virulence and to H. pylori's great genetic diversity.
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Affiliation(s)
- Daiva Dailidiene
- Department of Molecular Microbiology, Washington University Medical School, St. Louis, Missouri 63110, USA
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46
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Gerrits MM, de Zoete MR, Arents NLA, Kuipers EJ, Kusters JG. 16S rRNA mutation-mediated tetracycline resistance in Helicobacter pylori. Antimicrob Agents Chemother 2002; 46:2996-3000. [PMID: 12183259 PMCID: PMC127406 DOI: 10.1128/aac.46.9.2996-3000.2002] [Citation(s) in RCA: 83] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Most Helicobacter pylori strains are susceptible to tetracycline, an antibiotic commonly used for the eradication of H. pylori. However, an increase in incidence of tetracycline resistance in H. pylori has recently been reported. Here the mechanism of tetracycline resistance of the first Dutch tetracycline-resistant (Tet(r)) H. pylori isolate (strain 181) is investigated. Twelve genes were selected from the genome sequences of H. pylori strains 26695 and J99 as potential candidate genes, based on their homology with tetracycline resistance genes in other bacteria. With the exception of the two 16S rRNA genes, none of the other putative tetracycline resistance genes was able to transfer tetracycline resistance. Genetic transformation of the Tet(s) strain 26695 with smaller overlapping PCR fragments of the 16S rRNA genes of strain 181, revealed that a 361-bp fragment that spanned nucleotides 711 to 1071 was sufficient to transfer resistance. Sequence analysis of the 16S rRNA genes of the Tet(r) strain 181, the Tet(s) strain 26695, and four Tet(r) 26695 transformants showed that a single triple-base-pair substitution, AGA(926-928)-->TTC, was present within this 361-bp fragment. This triple-base-pair substitution, present in both copies of the 16S rRNA gene of all our Tet(r) H. pylori transformants, resulted in an increased MIC of tetracycline that was identical to that for the Tet(r) strain 181.
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Affiliation(s)
- Monique M Gerrits
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, The Netherlands
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47
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Boixeda D, Bermejo F, Martín-De-Argila C, López-Sanromán A, Defarges V, Hernández-Ranz F, Milicua JM, García-Plaza A. Efficacy of quadruple therapy with pantoprazole, bismuth, tetracycline and metronidazole as rescue treatment for Helicobacter pylori infection. Aliment Pharmacol Ther 2002; 16:1457-60. [PMID: 12182745 DOI: 10.1046/j.1365-2036.2002.01304.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
AIM To study the efficacy of a 7-day quadruple regimen combining pantoprazole, bismuth, tetracycline and metronidazole as rescue treatment for Helicobacter pylori infection after failure of standard triple therapy. METHODS A prospective study was made of 140 patients infected with H. pylori and diagnosed with peptic ulcer or non-ulcer dyspepsia in whom triple therapy with proton pump inhibitor, clarithromycin and amoxicillin had failed. The patients were treated with quadruple therapy including pantoprazole, 40 mg twice daily, colloidal bismuth subcitrate, 120 mg four times daily, tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily, for 7 days. Two months after completion of therapy, a 13C-urea breath test was performed to confirm eradication. RESULTS With quadruple therapy, the H. pylori eradication rates were 82% (95% confidence interval (CI), 75-88%) by 'intention-to-treat' and 85% (95% CI, 79-91%) by 'per protocol'. No major side-effects were observed. No differences in eradication success were observed in relation to underlying disease (peptic ulcer: 85% (95% CI, 76-91%) vs. non-ulcer dyspepsia: 83% (95% CI, 68-93%)) or smoking habits (smokers: 86% (95% CI, 75-93%) vs. non-smokers: 83% (95% CI, 71-91%)). CONCLUSION Quadruple therapy with pantoprazole, bismuth, tetracycline and metronidazole for 7 days is an effective H. pylori eradication treatment for patients in whom standard triple therapy has failed.
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Affiliation(s)
- D Boixeda
- Department of Gastroenterology, Ramón y Cajal Hospital, University of Alcalá, Madrid, Spain
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48
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Gisbert JP, Pajares JM. Review article: Helicobacter pylori "rescue" regimen when proton pump inhibitor-based triple therapies fail. Aliment Pharmacol Ther 2002; 16:1047-57. [PMID: 12030945 DOI: 10.1046/j.1365-2036.2002.01276.x] [Citation(s) in RCA: 178] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Even with the currently most effective treatment regimens, about 10-20% of patients will fail to obtain eradication of Helicobacter pylori infection. Therefore, in designing a treatment strategy, we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of second-line treatment depends on which treatment was used initially, as re-treatment with the same regimen is not recommended. Therefore, it is not necessary to perform culture after the first eradication failure. Assessment of the sensitivity of H. pylori to antibiotics only after failure of the second treatment is suggested in clinical practice. Different possibilities of empirical treatment have been suggested. After failure of proton pump inhibitor-amoxicillin-clarithromycin, quadruple therapy has generally been used. More recently, replacement of the proton pump inhibitor and the bismuth compound by ranitidine bismuth citrate has also achieved good results. After proton pump inhibitor-amoxicillin-nitroimidazole failure, re-treatment with proton pump inhibitor-amoxicillin-clarithromycin has been proven to be effective. Finally, first-line treatment should not combine clarithromycin and metronidazole in the same regimen, because of the problem of resistance to both antibiotics. Recently, rifabutin-based rescue therapies have been shown to constitute an encouraging strategy for eradication failures, as they are effective against H. pylori strains resistant to antibiotics.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital of La Princesa, Playa de Mojácar 29, Urb. Bonanza, 28669 Boadilla del Monte, Madrid, Spain.
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