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Zhou Y, Zhang Y, Du S. Antibiotic resistance in Helicobacter pylori among children and adolescents in East Asia: A systematic review and meta-analysis. Chin Med J (Engl) 2024; 137:1926-1938. [PMID: 38230488 PMCID: PMC11332731 DOI: 10.1097/cm9.0000000000002884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND In East Asia, Helicobacter pylori ( H. pylori ) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations. METHODS We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori , and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies. RESULTS We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40-62%) for metronidazole; 37% (95% CI: 20-53%) for clarithromycin; 19% (95% CI: 11-28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21-36%) and 10% (95% CI: 7-14%), highlighting the potential for diverse resistance patterns. CONCLUSIONS H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem. REGISTRATION PROSPERO, No. CRD42023402510.
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Affiliation(s)
- Yuhang Zhou
- Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yanli Zhang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shiyu Du
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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2
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Egli K, Wagner K, Keller PM, Risch L, Risch M, Bodmer T. Comparison of the Diagnostic Performance of qPCR, Sanger Sequencing, and Whole-Genome Sequencing in Determining Clarithromycin and Levofloxacin Resistance in Helicobacter pylori. Front Cell Infect Microbiol 2020; 10:596371. [PMID: 33392106 PMCID: PMC7773895 DOI: 10.3389/fcimb.2020.596371] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 11/17/2020] [Indexed: 12/21/2022] Open
Abstract
Helicobacter pylori antibiotic resistance is increasing worldwide, emphasizing the urgent need for more rapid resistance detection prior to the administration of H. pylori eradication regimens. Macrolides and fluoroquinolones are widely used to treat H. pylori. In this study, we aimed to compare the diagnostic performance of A) 23SrDNA qPCR (with melting curve analysis) and an in-house developed gyrA qPCR followed by Sanger sequencing with a commercial IVD-marked hybridization probe assay (for 23SrDNA and gyrA) using 142 gastric biopsies (skipping culturing) and B) the same two qPCR for 23SrDNA and gyrA (including Sanger sequencing) with whole-genome sequencing (WGS) and phenotypic characterization of clarithromycin and levofloxacin resistance using 76 cultured isolates. The sensitivity of both qPCRs was 100% compared to that of the commercial IVD-marked hybridization probe assay for the detection of H. pylori in gastric biopsies (without resistance testing). The specificity of the qPCR gyrA followed by Sanger sequencing was 100%, indicating that the best sequence identity was always H. pylori. The results show good agreement between molecular tests, especially between qPCR (inclusive Sanger sequencing) and WGS. Discrepancies (concerning mutated or wild type of positive H. pylori gastric biopsies) were observed between Sanger sequencing of the gyrA gene and the corresponding commercial hybridization probe assay, mostly because the high sequence diversity of the gyrA gene even at positions adjacent to the relevant codons of 87 and 91 interfered with obtaining correct results from the hybridization probe assay. Interestingly, we found several mixed sequences, indicating mixed populations in the gastric biopsies (direct detection without culturing). There was a high percentage of both levofloxacin and clarithromycin resistance in gastric biopsies (both between 22% and 29%, direct detection in gastric biopsies). Therefore, we recommend analyzing both targets in parallel. We confirmed that phenotypic resistance is highly correlated with the associated mutations. We concluded that the two qPCR followed by Sanger sequencing of the gyrA gene is a fast, cost-effective and comprehensive method for resistance testing of H. pylori directly in gastric biopsies.
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Affiliation(s)
- Konrad Egli
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland
| | - Karoline Wagner
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.,Laboratory Medicine, University Hospital of Basel, Basel, Switzerland
| | - Peter M Keller
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.,Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - Lorenz Risch
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland.,Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
| | - Martin Risch
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland
| | - Thomas Bodmer
- Labormedizinisches zentrum Dr Risch, Buchs, Switzerland
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3
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Hanafiah A, Binmaeil H, Raja Ali RA, Mohamed Rose I, Lopes BS. Molecular characterization and prevalence of antibiotic resistance in Helicobacter pylori isolates in Kuala Lumpur, Malaysia. Infect Drug Resist 2019; 12:3051-3061. [PMID: 31632095 PMCID: PMC6774992 DOI: 10.2147/idr.s219069] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 07/25/2019] [Indexed: 12/12/2022] Open
Abstract
Aims and objectives Helicobacter pylori has been classified as high priority pathogen by the WHO in 2017. The emergence of antibiotic-resistant strains is one of the main causes of treatment failure in H. pylori infection. This study determined and characterized primary and secondary resistances in H. pylori in Malaysia. Materials and methods Gastric biopsies from antrum (n=288) and corpus (n=283) were obtained from 288 patients who underwent endoscopy at Universiti Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. Antibiotic susceptibility to six classes of antibiotics was determined by the E-test. Mutations conferring in resistance in functional genes were identified by PCR and sequencing. Results Overall resistance rates to metronidazole, clarithromycin and levofloxacin were 59.3% (35/59), 35.6% (21/59) and 25.4% (15/59), respectively. Secondary isolates showed significantly higher resistance rates to clarithromycin compared to the primary isolates. Mixed infection with susceptible and resistant isolates was observed in 16.2% (6/37) of cases, of which 83.3% (n=5) had infection with the same strain. 41% (18/44) of isolates were resistant to more than one class of antibiotics of which 50% (9/18) were multidrug-resistant, two being primary and seven being secondary isolates. Mutations in rdxA, 23S rRNA and gyrA genes were associated with resistance to metronidazole, clarithromycin and levofloxacin, respectively. Conclusion The high level of resistance to metronidazole, clarithromycin and levofloxacin seen in H. pylori isolates in our setting warrants the need for continuous surveillance and highlights caution in use of antibiotics generally used as first-line therapy in H. pylori eradication regimen.
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Affiliation(s)
| | | | | | - Isa Mohamed Rose
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia
| | - Bruno S Lopes
- Department of Medical Microbiology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
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4
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Mori H, Suzuki H, Matsuzaki J, Masaoka T, Kanai T. Acquisition of double mutation in gyrA caused high resistance to sitafloxacin in Helicobacter pylori after unsuccessful eradication with sitafloxacin-containing regimens. United European Gastroenterol J 2018; 6:391-397. [PMID: 29774152 PMCID: PMC5949976 DOI: 10.1177/2050640617737215] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Accepted: 09/14/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIM Although sitafloxacin (STFX)-containing regimens are effective rescue treatments for Helicobacter pylori infection, prevalence of fluoroquinolone resistance in H. pylori has increased rapidly worldwide. The change in resistance levels and gyrA mutations, a major cause of fluoroquinolone resistance, after unsuccessful STFX-containing treatment has not been investigated. METHODS We conducted a retrospective, non-randomized study to compare the minimum inhibitory concentrations (MICs) of STFX and the location of gyrA mutations in H. pylori before and after unsuccessful eradication with STFX-containing regimens at Keio University Hospital between December 2011 and March 2015. RESULTS A total of 266 patients treated with STFX-containing regimens for third-line H. pylori eradication were evaluated. Double mutations in gyrA were acquired by 20.8% of strains that exhibited seven-fold increased STFX MICs, compared to pre-treatment MICs. The STFX MICs did not increase, however, when the location of the gyrA mutations did not change after treatment. Double mutations in gyrA developed in 60.0% of the strains in which eradication failed, which exhibited a baseline mutation at position D91, and in 11.1% of strains with baseline mutations at position N87. CONCLUSION Acquisition of double mutations in gyrA evoked high-level resistance to STFX in H. pylori after unsuccessful eradication with STFX-containing regimens.
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Affiliation(s)
- Hideki Mori
- Division of Gastroenterology and
Hepatology, Department of Internal Medicine, Keio University School of Medicine,
Tokyo, Japan
- Department of Gastroenterology, National
Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Hidekazu Suzuki
- Medical Education Center, Keio
University School of Medicine, Tokyo, Japan
| | - Juntaro Matsuzaki
- Division of Gastroenterology and
Hepatology, Department of Internal Medicine, Keio University School of Medicine,
Tokyo, Japan
- Division of Molecular and Cellular
Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Tatsuhiro Masaoka
- Division of Gastroenterology and
Hepatology, Department of Internal Medicine, Keio University School of Medicine,
Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and
Hepatology, Department of Internal Medicine, Keio University School of Medicine,
Tokyo, Japan
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5
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Urushibara N, Suzaki K, Kawaguchiya M, Aung MS, Shinagawa M, Takahashi S, Kobayashi N. Contribution of Type II Topoisomerase Mutations to Fluoroquinolone Resistance inEnterococcus faeciumfrom Japanese Clinical Setting. Microb Drug Resist 2018; 24:1-7. [DOI: 10.1089/mdr.2016.0328] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Noriko Urushibara
- Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keisuke Suzaki
- Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Mitsuyo Kawaguchiya
- Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Meiji Soe Aung
- Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masaaki Shinagawa
- Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan
| | - Satoshi Takahashi
- Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Nobumichi Kobayashi
- Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo, Japan
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Mori H, Suzuki H, Matsuzaki J, Masaoka T, Kanai T. Antibiotic resistance and gyrA mutation affect the efficacy of 10-day sitafloxacin-metronidazole-esomeprazole therapy for Helicobacter pylori in penicillin allergic patients. United European Gastroenterol J 2017; 5:796-804. [PMID: 29026593 PMCID: PMC5625875 DOI: 10.1177/2050640616688995] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 12/20/2016] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) eradication regimen has not been standardized for patients with penicillin allergy. We investigated the association between the efficacy of a 10-day sitafloxacin, metronidazole, and esomeprazole triple regimen and antibiotic resistance, in patients with penicillin allergy. METHODS Penicillin-allergic patients infected with H. pylori were enrolled between March 2014 and November 2015. The minimum inhibitory concentrations (MICs) of sitafloxacin and metronidazole, and the gyrA mutation status of the H. pylori strains were determined before treatment. The cut-off points for antimicrobial resistance were defined as 8.0 µg/ml for metronidazole and 0.12 µg/ml for sitafloxacin. The patients received the triple therapy (20 mg esomeprazole, bid; 250 mg metronidazole, bid; and 100 mg sitafloxacin, bid) for 10 days. Successful eradication was evaluated using the [13C] urea breath test or the H. pylori stool antigen test. RESULTS Fifty-seven patients were analyzed, and the overall eradication rate was 89.5%. The eradication rate in cases of double antibiotic resistance to metronidazole and sitafloxacin was 40.0%, whereas for other combinations of resistance, this was above 90.0%. Finally, the eradication rate of gyrA mutation-negative strains was 96.2%, whereas for gyrA mutation-positive strains, it was 83.9%. Adverse events were reported in 31.6% of cases, all of which were mild and tolerable. CONCLUSION Ten days of sitafloxacin and metronidazole triple therapy was safe and highly effective in eradicating H. pylori in penicillin-allergic patients. Double resistance to metronidazole and sitafloxacin was an important predicting factor for eradication failure. However, 10 days of the sitafloxacin and metronidazole triple therapy was highly effective if the strain was susceptible to either sitafloxacin or metronidazole.
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Affiliation(s)
- Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Hidekazu Suzuki
- Medical Education Center, Keio University School of Medicine, Tokyo, Japan
| | - Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Tatsuhiro Masaoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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7
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Doosti A, Mokhtari-Farsani A, Chehelgerdi M. Molecular Characterization of Gyr-A
Gene Polymorphism in Salmonella Enterica
Serovar Enteritidis Isolated of Egg Shells. J Food Saf 2016. [DOI: 10.1111/jfs.12276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Abbas Doosti
- Biotechnology Research Center, Islamic Azad University; Shahrekord Branch Shahrekord Iran
| | - Abbas Mokhtari-Farsani
- Biotechnology Research Center, Islamic Azad University; Shahrekord Branch Shahrekord Iran
- Young Researchers and Elite Club, Shahrekord Branch; Islamic Azad University; Shahrekord Iran
| | - Mohammad Chehelgerdi
- Biotechnology Research Center, Islamic Azad University; Shahrekord Branch Shahrekord Iran
- Young Researchers and Elite Club, Shahrekord Branch; Islamic Azad University; Shahrekord Iran
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Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Uotani T, Sahara S, Ichikawa H, Yamada T, Osawa S, Sugimoto K, Watanabe H, Umemura K. Sitafloxacin-based third-line rescue regimens for Helicobacter pylori infection in Japan. J Gastroenterol Hepatol 2014; 29:487-93. [PMID: 24224808 DOI: 10.1111/jgh.12442] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUNDS Quinolone-based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin-based eradication regimens as rescue for the eradication of H. pylori. METHODS We attempted to eradicate H. pylori in 180 Japanese patients who had never failed in eradication of H. pylori with the triple proton pump inhibitor/amoxicillin/clarithromycin therapy (1st line) and the triple proton pump inhibitor/amoxicillin/metronidazole therapy (2nd line). They were assigned to either the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., amoxicillin 500 mg q.i.d, and sitafloxacin 100 mg b.i.d. (RAS) for 1 or 2 weeks or the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., metronidazole 250 mg b.i.d., and sitafloxacin 100 mg b.i.d. (RMS) for 1 or 2 weeks. Eradication was assessed via the (13) C-urea breath test and rapid urease test. RESULTS Intention-to-treat and per-protocol analyses of eradication rates were 84.1% (37/44) and 86.4% (37/43) with RAS for 1 week, 88.9% (40/45) and 90.9% (40/44) for RAS for 2 weeks, 90.9% (40/44) and 90.9% (40/44) for 1 week-RMS and 87.2% (41/47) and 91.1% (41/45) with RMS for 2 weeks. We noted no statistical significant differences in eradication rates among four regimens. CONCLUSION All of the above-described rescue regimens proved relatively equally useful in the eradication of H. pylori. Of them, RAS for 2 weeks and RMS for 1 or 2 weeks could attain the rescue eradication rates higher than 90% by per-protocol analysis.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Abstract
Helicobacter pylori (H. pylori) has been identified as the most important risk factor for chronic active gastritis and peptic ulcer disease. Resistance to antibiotics is increasing in H. pylori and is the main reason for failure of H. pylori eradication therapy. It is now widely accepted that resistance to fluoroquinolones (levofloxacin) is related with mutations of H. pylori gyrA gene. Molecular mechanisms of and detection methods for H. pylori resistance to levofloxacin have become the focus of current research. Therefore, study on H. pylori resistance to antibiotics is of great significance for eradication therapy of H. pylori infection.
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Abstract
GOALS To determine the susceptibility of Helicobacter pylori strains isolated from a Vietnamese population to 5 antibiotics. BACKGROUND The incidence of antibiotic resistance in H. pylori infection is increasing worldwide and has become a leading cause for failure of treatment. Antibiotic susceptibility testing is very important to provide optimal regimens in a clinical setting. STUDY We isolated 103 H. pylori strains from the gastric mucosa of H. pylori-infected patients from 2 areas in Vietnam (Ho Chi Minh and Hanoi) in 2008. Epsilometer test was used to determine the minimum inhibitory concentrations of amoxicillin, clarithromycin (CLR), metronidazole (MNZ), levofloxacin, and tetracycline. RESULTS Among the 103 strains, the resistance rates were 0% (amoxicillin), 33% (CLR), 69.9% (MNZ), 18.4% (levofloxacin), and 5.8% (tetracycline). The resistant strains showed a high-level of resistance (≥ 256 µg/mL) to CLR, 23.5% (8/34), and MNZ, 29.1% (21/72). The resistance rate for CLR was significantly higher in Ho Chi Minh than in Hanoi (49% vs. 18.5%, P=0.001). Resistance to both CLR and MNZ was most commonly observed (24.3%). Two strains (1.9%) were resistant to 4 of the 5 antibiotics. No significant association was observed between antibiotic resistance rates and age, sex, or clinical outcomes of the patients. CONCLUSIONS High incidence of resistance to CLR and MNZ suggests that standard triple therapies may not be useful as first-line treatment in Vietnam. Alternative strategies such as bismuth-based quadruple therapies or sequential therapy may be more effective in Vietnam.
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Caro SD, Fini L, Daoud Y, Grizzi F, Gasbarrini A, Lorenzo AD, Renzo LD, McCartney S, Bloom S. Levofloxacin/amoxicillin-based schemes vs quadruple therapy for Helicobacter pylori eradication in second-line. World J Gastroenterol 2012; 18:5669-78. [PMID: 23155306 PMCID: PMC3484334 DOI: 10.3748/wjg.v18.i40.5669] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2012] [Revised: 05/29/2012] [Accepted: 06/08/2012] [Indexed: 02/06/2023] Open
Abstract
Worldwide prevalence of Helicobacter pylori (H. pylori) infection is approximately 50%, with the highest being in developing countries. We compared cure rates and tolerability (SE) of second-line anti-H. pylori levofloxacin/amoxicillin (LA)-based triple regimens vs standard quadruple therapy (QT). An English language literature search was performed up to October 2010. A meta-analysis was performed including randomized clinical trials comparing 7- or 10-d LA with 7-d QT. In total, 10 articles and four abstracts were identified. Overall eradication rate in LA was 76.5% (95% CI: 64.4%-97.6%). When only 7-d regimens were included, cure rate was 70.6% (95% CI: 40.2%-99.1%), whereas for 10-d combinations, cure rate was significantly higher (88.7%; 95% CI: 56.1%-109.9%; P < 0.05). Main eradication rate for QT was 67.4% (95% CI: 49.7%-67.9%). The 7-d LA and QT showed comparable efficacy [odds ratio (OR): 1.09; 95% CI: 0.63-1.87], whereas the 10-d LA regimen was significantly more effective than QT (OR: 5.05; 95% CI: 2.74-9.31; P < 0.001; I2 = 75%). No differences were reported in QT eradication rates among Asian and European studies, whereas LA regimens were more effective in European populations (78.3% vs 67.7%; P = 0.05). Incidence of SE was lower in LA therapy than QT (OR: 0.39; 95% CI: 0.18-0.85; P = 0.02). A higher rate of side effects was reported in Asian patients who received QT. Our findings support the use of 10-d LA as a simple second-line treatment for H. pylori eradication with an excellent eradication rate and tolerability. The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.
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Garcia M, Raymond J, Garnier M, Cremniter J, Burucoa C. Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France. Antimicrob Agents Chemother 2012; 56:550-1. [PMID: 22064536 PMCID: PMC3256052 DOI: 10.1128/aac.05243-11] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Accepted: 10/24/2011] [Indexed: 01/30/2023] Open
Abstract
We determined the prevalence of gyrA mutations conferring fluoroquinolone resistance in 97 Helicobacter pylori isolates collected in France from 2007 to 2010. Ninety-four harbored one or two mutations already found in the quinolone resistance determining region (QRDR) of gyrA (for T87I, n = 23; for N87K, n = 32; for D91N, n = 30; for D91G, n = 7; for D91Y, n = 6), 2 harbored a mutation never previously described (D91H and A88P), and one strain was resistant (ciprofloxacin MIC of 8 mg/liter) without a detected mutation conferring this resistance in gyrA or gyrB genes.
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Affiliation(s)
- Magali Garcia
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
| | - Josette Raymond
- CHU Cochin Port Royal, Unité Postulante de Pathogénèse de Helicobacter, Institut Pasteur, Paris, France
| | - Martine Garnier
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
| | - Julie Cremniter
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
| | - Christophe Burucoa
- EA 4331 LITEC, Université de Poitiers, CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
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13
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Francesco VD, Zullo A, Hassan C, Giorgio F, Rosania R, Ierardi E. Mechanisms of Helicobacter pylori antibiotic resistance: An updated appraisal. World J Gastrointest Pathophysiol 2011; 2:35-41. [PMID: 21860834 PMCID: PMC3158889 DOI: 10.4291/wjgp.v2.i3.35] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Revised: 05/29/2011] [Accepted: 06/05/2011] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) antibiotic resistance is the main factor affecting the efficacy of the current eradicating therapies. The aim of this editorial is to report on the recent information about the mechanisms accounting for the resistance to the different antibiotics currently utilized in H. pylori eradicating treatments. Different mechanisms of resistance to clarithromycin, metronidazole, quinolones, amoxicillin and tetracycline are accurately detailed (point mutations, redox intracellular potential, pump efflux systems, membrane permeability) on the basis of the most recent data available from the literature. The next hope for the future is that by improving the knowledge of resistance mechanisms, the elaboration of rational and efficacious associations for the treatment of the infection will be possible. Another auspicious progress might be the possibility of a cheap, feasible and reliable laboratory test to predict the outcome of a therapeutic scheme.
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Ahmad N, Zakaria WR, Mohamed R. Analysis of antibiotic susceptibility patterns of Helicobacter pylori isolates from Malaysia. Helicobacter 2011; 16:47-51. [PMID: 21241412 DOI: 10.1111/j.1523-5378.2010.00816.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prevalence of antibiotic resistance varies in geographic areas. The information on the antibiotic susceptibility patterns of Helicobacter pylori (H. pylori) in our local setting is therefore relevant as a guide for the treatment options. OBJECTIVE This study was conducted to determine the primary resistance rates among H. pylori isolated from Malaysian patients. MATERIALS AND METHODS Biopsy samples were obtained from the stomach antrum and corpus of 777 patients from September 2004 until 2007. H. pylori isolated from these patients were then subjected to minimum inhibitory concentration (MICs) determination using E-test method, against metronidazole, clarithromycin, levofloxacin, ciprofloxacin, amoxicillin, and tetracycline. RESULTS From 777 patients, 119 were positive for H. pylori where a total of 187 strains were isolated. The resistance rates were noted to be 37.4% (metronidazole), 2.1% (clarithromycin), 1% (levofloxacin and ciprofloxacin), and 0% (amoxicillin and tetracycline). Different resistance profiles were observed among isolates from the antrum and corpus of 13 patients. Resistance to one type of antibiotic was observed in 36.4% of the strains where mono-resistance to metronidazole was the most common. Resistance to ≥2 antibiotics was noted in 3.3% of isolates. High metronidazole MICs of ≥256 μg/mL were observed among the resistant strains. CONCLUSIONS The resistance rates of the antibiotics used in primary treatment of H. pylori infections in Malaysia are low, and multi-antibiotic-resistant strains are uncommon. Infections with mixed populations of metronidazole-sensitive and -resistant strains were also observed. However, the high metronidazole MIC values seen among the metronidazole-resistant strains are a cause for concern.
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Affiliation(s)
- Norazah Ahmad
- Bacteriology Unit, Institute for Medical Research, Jalan Pahang, 50588, Kuala Lumpur, Malaysia.
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Pan X, Li Y, Qiu Y, Tang Q, Qian B, Yao L, Shi R, Zhang G. Efficacy and tolerability of first-line triple therapy with levofloxacin and amoxicillin plus esomeprazole or rabeprazole for the eradication of Helicobacter pylori infection and the effect of CYP2C19 genotype: A 1-week, randomized, open-label study in chinese adults. Clin Ther 2010; 32:2003-11. [PMID: 21118735 DOI: 10.1016/j.clinthera.2010.11.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/21/2010] [Indexed: 01/02/2023]
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Change in antibiotic resistance of Helicobacter pylori strains and the effect of A2143G point mutation of 23S rRNA on the eradication of H. pylori in a single center of Korea. J Clin Gastroenterol 2010; 44:536-43. [PMID: 20179610 DOI: 10.1097/mcg.0b013e3181d04592] [Citation(s) in RCA: 110] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The current prevalence of primary antibiotic resistance of H. pylori is not known in Korea. This study was done to evaluate the prevalence of primary antibiotic resistance of H. pylori, and to evaluate the effect of point mutations of 23S rRNA on the rate of eradication of H. pylori. METHODS H. pylori were isolated from gastric mucosal biopsy specimens obtained from 222 Koreans. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin were examined using the agar dilution method. DNA sequencing was carried out to detect H. pylori 23S rRNA mutations. RESULTS The resistance to clarithromycin, tetracycline, ciprofloxacin, and levofloxacin increased during the period of 2007 to 2009 compared with 2003 to 2005 (P<0.05). However, amoxicillin and metronidazole resistance slightly decreased. The rates of eradication were 95.5% for the clarithromycin-sensitive strains, which was higher than the 67.9% for the clarithromycin-resistant strains (P=0.001). By contrast, the eradication rate was 100% in patients with amoxicillin-resistant H. pylori. Among 26 clarithromyin-resistant strains, 6 (23%) had A2143G mutations, and all of the cases in which these mutations were present were not eradicated by proton pump inhibitor-based triple therapy (P=0.0004). By contrast, none of the 26 clarithromyin-sensitive strains had A2143G mutations. The T2183C and A2223G mutations were frequently found in the sensitive strains and in the resistant strains. CONCLUSIONS Clarithromycin resistance of H. pylori, which determined the efficacy of H. pylori eradication of proton pump inhibitor triple regimen, was found to be increased in a single center study. A2143G was an important 23S rRNA mutation associated with clarithromycin resistance and affected the H. pylori eradication efficacy.
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Yang JC, Lee PI, Hsueh PR. In vitro activity of nemonoxacin, tigecycline, and other antimicrobial agents against Helicobacter pylori isolates in Taiwan, 1998-2007. Eur J Clin Microbiol Infect Dis 2010; 29:1369-75. [PMID: 20658256 DOI: 10.1007/s10096-010-1009-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2010] [Accepted: 06/20/2010] [Indexed: 12/17/2022]
Abstract
The minimum inhibitory concentrations (MICs) of 330 nonduplicate Helicobacter pylori isolates to nemonoxacin, tigecycline, and eight other antimicrobial agents were determined by using the agar dilution method. Sequencing the quinolone resistance-determining regions (QRDRs) in the gyrA gene of these isolates was also performed. Resistance to clarithromycin showed an increasing trend during the ten-year study period and was highest (38%) in 2005. Tigecycline had potent in vitro activities against all isolates, with an MIC(90) of 0.06 μg/ml. Among the quinolones tested, nemonoxacin (MIC(50) of 0.12 μg/ml and MIC(90) of 0.25 μg/ml) and gemifloxacin had one to two-fold better in vitro activities than ciprofloxacin, levofloxacin, and moxifloxacin. Among the nine isolates (2.7%) with levofloxacin resistance, four (44.4%) were also resistant to metronidazole, three (33.3%) to clarithromycin, and two (22.2%) to amoxicillin. Isolates with levofloxacin resistance exhibited one or two of three amino acid alterations (Ser-70, Asn-87, and Asp-91) involved in QRDRs in the gyrA gene. A double mutation at Ser70Cys and Asn87Ile had a higher level of resistance. The results of this study suggest a potentially useful role of nemonoxacin and tigecycline in the treatment of infections caused by H. pylori. The gyrA mutation at Ser-70 is a novel finding and has an impact on levofloxacin resistance.
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Affiliation(s)
- J-C Yang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Boyanova L, Mitov I. Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. Expert Rev Anti Infect Ther 2010; 8:59-70. [PMID: 20014902 DOI: 10.1586/eri.09.113] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Antibiotic resistance in Helicobacter pylori is the major cause of eradication failure. Primary H. pylori susceptibility patterns, however, are becoming less predictable. Currently, high (> or =20%) clarithromycin resistance rates have been observed in the USA and in developed countries in Europe and Asia, while the highest (> or =80%) metronidazole-resistance rates have been reported in Africa, Asia and South America. Primary quinolone-resistance rates of 10% or more have already been reported in developed countries in Europe and Asia. Primary amoxicillin resistance has been low (0 to <2%) in Europe but higher (6-59%) in Africa, Asia and South America. Similarly, tetracycline resistance has been absent or low (<5%) in most countries and higher (9-27%) in Asia and South America. The increasing clarithromycin and quinolone resistance, and multidrug resistance detected in 0 to less than 5% in Europe and more often (14.2%) in Brazil are worrying. Growing resistance often parallels national antibiotic consumption and may vary within patient groups according to the geographic region, patient's age and sex, type of disease, birthplace, other infections and other factors. The geographic map and evolution of primary H. pylori resistance are clinically important, should be considered when choosing eradication regimens, and should be monitored constantly at national and global levels in an attempt to reach the recently recommended goal of eradication of more than 95%.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, Zdrave street 2, 1431 Sofia, Bulgaria.
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Chisholm SA, Owen RJ. Frequency and molecular characteristics of ciprofloxacin- and rifampicin-resistant Helicobacter pylori from gastric infections in the UK. J Med Microbiol 2009; 58:1322-1328. [PMID: 19589906 DOI: 10.1099/jmm.0.011270-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Treatment failure with standard Helicobacter pylori eradication regimes may require the use of 'rescue' therapies containing fluoroquinolones or rifamycins. The susceptibilities of H. pylori in the UK to such antimicrobials are unknown; therefore, this study aimed to determine the frequencies and molecular markers of resistance. Ciprofloxacin and rifampicin susceptibilities were determined by Etest and/or disc diffusion for 255 isolates of H. pylori, including 171 isolates from adult dyspeptic patients with refractive infections. Mutations in known resistance-determining regions of gyrA and rpoB were determined. The ciprofloxacin resistance rate was 7.5 %, and gyrA mutations, predominantly at codon position 91, were identified in most resistant isolates. One isolate (<1 %) had an unequivocal rifampicin-resistant phenotype by Etest yet had no associated mutations in the rpoB gene. As resistance rates were low in H. pylori isolates, including those from patients with refractive infections, it was concluded that fluoroquinolones or rifamycins might be considered in the UK for inclusion in 'rescue' therapies.
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Affiliation(s)
- Stephanie A Chisholm
- Gastrointestinal, Emerging and Zoonotic Infections Department, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5HT, UK
| | - Robert J Owen
- Gastrointestinal, Emerging and Zoonotic Infections Department, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5HT, UK
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Kuo CH, Hu HM, Kuo FC, Hsu PI, Chen A, Yu FJ, Tsai PY, Wu IC, Wang SW, Li CJ, Weng BC, Chang LL, Jan CM, Wang WM, Wu DC. Efficacy of levofloxacin-based rescue therapy for Helicobacter pylori infection after standard triple therapy: a randomized controlled trial. J Antimicrob Chemother 2009; 63:1017-24. [PMID: 19246508 DOI: 10.1093/jac/dkp034] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES This prospective study was designed to determine the efficacy of a levofloxacin-based rescue therapy for Helicobacter pylori infection after failure of standard triple therapies. We also surveyed the predictors of this rescue therapy. PATIENTS AND METHODS From June 2005 to March 2007, 1036 patients infected with H. pylori received standard triple regimens (proton pump inhibitor, clarithromycin and amoxicillin). H. pylori eradication was achieved in 855 (82.5%) subjects. One hundred and sixty-six eradication-failure patients were enrolled and randomly assigned to receive a 7 day eradication therapy with esomeprazole, bismuth subcitrate, tetracycline and metronidazole (EBTM) or esomeprazole, amoxicillin and levofloxacin (EAL). Follow-up endoscopy was done 16 weeks later to assess the treatment response. Patients' response, CYP2C19 genotypes and antibiotic resistances were also examined. RESULTS Intention-to-treat analysis revealed that both groups showed similar eradication rates [EBTM 63.9%; 95% confidence interval (CI): 53.6-74.2 and EAL 69.9%; 95% CI: 60.1-79.7] (P = 0.89). Per-protocol results were EBTM = 84.1% (95% CI: 75.1-93.1) and EAL = 75.3% (95% CI: 65.8-84.8) (P = 0.82). Both regimens had similar compliance (P = 0.32), but the EBTM group had more adverse events (P = 0.27). Logistic regression analysis showed that poor compliance, CYP2C19 homozygous extensive metabolizer genotype and levofloxacin resistance were important predictors for eradication failure. CONCLUSIONS The EAL regimen can achieve an efficacy similar to that of the standard EBTM therapy. It may be very useful in countries where bismuth salts are not available. Compliance, CYP2C19 genotype and resistances to antibiotics may influence the outcome of levofloxacin-based rescue therapy. It seems advisable to reserve levofloxacin for rescue treatment to avoid an increase in the resistance phenomenon.
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Sitafloxacin and garenoxacin may overcome the antibiotic resistance of Helicobacter pylori with gyrA mutation. Antimicrob Agents Chemother 2009; 53:1720-1. [PMID: 19188389 DOI: 10.1128/aac.00049-09] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Nishizawa T, Suzuki H, Nakagawa I, Iwasaki E, Masaoka T, Hibi T. Gatifloxacin-based triple therapy as a third-line regimen for Helicobacter pylori eradication. J Gastroenterol Hepatol 2008; 23 Suppl 2:S167-70. [PMID: 19120892 DOI: 10.1111/j.1440-1746.2008.05407.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM This study was designed to investigate the efficacy of gatifloxacin (GAT)-based triple therapy as a third-line treatment for Helicobacter pylori (H. pylori) eradication, according to the assessment of the susceptibility to GAT and gyrA mutation. METHODS Fourteen patients who had eradication failure following both clarithromycin-based triple therapy and metronidazole-based triple therapy, or who were infected with H. pylori isolates that were resistant to both clarithromycin and metronidazole after failure of clarithromycin-based triple therapy, were enrolled. These patients were randomly assigned to two groups: (i) rabeprazole and amoxicillin (RA) and (ii) rabeprazole, amoxicillin, and GAT for 7 days (RAG). The minimal inhibitory concentrations were determined by the agar dilution method. The gyrA gene was examined by sequencing. RESULTS The eradication rate was 0% in the RA group and 75% in the RAG group. The eradication rate in the RAG group was 100% in patients infected with GAT-susceptible bacteria and/or bacteria without gyrA mutations, but was only 33.3% in those infected with GAT-resistant bacteria or bacteria with gyrA mutations. CONCLUSION Although GAT may be a promising candidate for third-line therapy, its selection must be based on the results of drug susceptibility testing or gyrA analyses.
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Affiliation(s)
- Toshihiro Nishizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
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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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Lee CC, Lee VWY, Chan FKL, Ling TKW. Levofloxacin-resistant Helicobacter pylori in Hong Kong. Chemotherapy 2007; 54:50-3. [PMID: 18073471 DOI: 10.1159/000112416] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2006] [Accepted: 06/03/2007] [Indexed: 12/17/2022]
Abstract
BACKGROUND Fluoroquinolone-resistant Helicobacter pylori emerged in 1995 and the resistance was due to point mutation in the gyrA gene. In this study we investigate the resistance mechanism and the antimicrobial susceptibilities of clarithromycin, metronidazole, amoxicillin, tetracycline and telithromycin against levofloxacin-resistant H. pylori in Hong Kong. METHODS One hundred and ninety-one nonduplicate H. pylori isolates were collected during 2004 and 2005, and 25 isolates with levofloxacin zone sizes less than 30 mm were selected for minimal inhibitory concentration determination by agar dilution, gyrA gene amplication and sequencing the amplified gyrA gene. RESULTS The prevalence of levofloxacin-resistant H. pylori was 11.5% (22/191). Among these levofloxacin-resistant strains, 7 (31.8%) and 10 (45.5%) were resistant to clarithromycin and metronidazole, respectively, 17 (77.3%) had point mutations in gyrA gene at amino acids 87, 91 and 130 and the most frequent mutation point was at position 91. CONCLUSIONS Amoxicillin, tetracycline and telithromycin were active against levofloxacin-resistant H. pylori and levofloxacin resistance was mainly due to point mutation in the gyrA gene, especially at amino acid position 91.
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Affiliation(s)
- Ching Ching Lee
- Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China
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Perna F, Zullo A, Ricci C, Hassan C, Morini S, Vaira D. Levofloxacin-based triple therapy for Helicobacter pylori re-treatment: role of bacterial resistance. Dig Liver Dis 2007; 39:1001-5. [PMID: 17889627 DOI: 10.1016/j.dld.2007.06.016] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2007] [Revised: 05/21/2007] [Accepted: 06/28/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND First-line Helicobacter pylori therapy fails in more than 20% of patients. Quadruple therapy is the suggested second-line therapy, but bismuth salts are not anymore available worldwide. This study aimed to assess the efficacy of a levofloxacin-amoxycillin triple therapy as a second-line treatment, and the role of primary levofloxacin resistance. METHODS Forty patients, in whom first treatment with either standard 10-day triple or sequential therapy had failed, received 10-day triple therapy with rabeprazole (20mg b.d.), levofloxacin (250mg b.d.), and amoxycillin (1g b.d.). Cure rates were evaluated by the (13)C-urea breath test. Primary levofloxacin resistance was detected by culture. RESULTS Bacterial culture was available in 33 (82.5%) out 40 patients, and primary levofloxacin resistance was detected in 10 (30.3%) patients. Overall, 33 of 40 patients accepted to participate in this study, and all returned for follow-up after therapy. Compliance to the therapy was safe except 1 patient only who stopped earlier the treatment due to side effects (oral candidiasis). H. pylori infection was eradicated in 24 patients, accounting for a 72.7% (95% CI: 57-88) eradication rate at both intention-to-treat and per protocol analyses. The eradication rate was higher in patients harbouring levofloxacin-susceptible than resistant strains (75% versus 33.3%; P=0.074). CONCLUSIONS The eradication rate achieved by a levofloxacin-based re-treatment seems to be decreasing, and its efficacy is reduced in presence of levofloxacin resistance.
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Affiliation(s)
- F Perna
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy
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Lin GY. Progress in research into the molecular mechanism of drug resistance of Helicobacter pylori. Shijie Huaren Xiaohua Zazhi 2007; 15:2698-2703. [DOI: 10.11569/wcjd.v15.i25.2698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a pathogen of chronic and active gastritis. It is the main cause of chronic gastritis and peptic ulcer disease, and is directly related to diseases of the stomach and duodenum. This pathogen can also induce gastric carcinoma. With the extensive use of antibiotics, the number of drug resistant strains of H. pylori has rapidly increased. As a result, there are some difficulties in applying clinical therapy for diseases related to H. pylori. This paper aimed to first analyze the status and prevalence of antibiotic resistance, and then to review various drugs such as macrolides, imidazoles, tetracyclines, β-lactams and quinolones for systematically treating H. pylori infection. The mechanisms of various drug resistances, as well as detection and identification assays for typing drug resistance, are discussed. This paper presents accumulated clinical data and evidence for the clinical diagnosis and treatment of diseases related to H. pylori.
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Abstract
Eradication therapy for Helicobacter pylori is recommended in a number of clinical conditions. In this article, we discuss the epidemiology and cellular mechanisms that result in antimicrobial resistance, the results of current eradication therapies, and new approaches to the management of Helicobacter pylori infection.
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Affiliation(s)
- Nimish Vakil
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
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Zullo A, De Francesco V, Scaccianoce G, Manes G, Efrati C, Hassan C, Maconi G, Piglionica D, Cannaviello C, Panella C, Morini S, Ierardi E. Helicobacter pylori eradication with either quadruple regimen with lactoferrin or levofloxacin-based triple therapy: a multicentre study. Dig Liver Dis 2007; 39:806-10. [PMID: 17644057 DOI: 10.1016/j.dld.2007.05.021] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2007] [Revised: 05/07/2007] [Accepted: 05/21/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND Helicobacter pylori eradication rate following standard triple therapy is decreasing worldwide. A quadruple therapy with lactoferrin and a levofloxacin-based triple therapy has been found to achieve a very high (>90%) cure rate. This study aimed to confirm these encouraging results. METHODS This was a prospective, open-label, randomised, multicentre, Italian study enrolling consecutive H. pylori infected patients. The infection at entry was assessed by endoscopy and biopsies (histology plus rapid urease test) in all patients, whilst bacterial eradication was assessed by 13C-urea breath test 4-6 weeks after therapy ended. Patients were randomised to receive either a 7-day, triple therapy with rabeprazole 20mg o.d., levofloxacin 500 mg o.d., and amoxycillin 1g b.i.d. (4 tablets/day) or a 7-day quadruple therapy comprising of rabeprazole 20mg, clarithromycin 500 mg, tinidazole 500 mg plus bovine lactoferrin 200mg, all given twice daily (10 tablets/day). RESULTS Overall, 144 consecutive patients were enrolled in the study. Following the triple therapy, H. pylori infection was cured in 49 out of 72 (68.1%; 95% CI=57-79) patients and in 49 out of 71 (69.1%; 95% CI=58-80) at intention-to-treat and per protocol analyses, respectively. Following the quadruple regimen, the infection was cured in 52 out of 72 (72.2%; 95% CI=62-83) and in 52 out of 68 (76.5; 95% CI=66-87) patients at intention-to-treat and per protocol analyses, respectively. No statistically significant difference emerged between the two therapy regimens. CONCLUSIONS H. pylori eradication rate following both quadruple therapy with lactoferrin and a low-dose PPI, triple therapy with levofloxacin is disappointingly low.
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Affiliation(s)
- A Zullo
- Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy.
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Cattoir V, Nectoux J, Lascols C, Deforges L, Delchier JC, Megraud F, Soussy CJ, Cambau E. Update on fluoroquinolone resistance in Helicobacter pylori: new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility. Int J Antimicrob Agents 2007; 29:389-96. [PMID: 17303392 DOI: 10.1016/j.ijantimicag.2006.11.007] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2006] [Revised: 11/07/2006] [Accepted: 11/07/2006] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. pylori strains isolated in 2004-2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC(50) = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 91, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a 'test and treat' strategy that can confidently rely on QRDR gyrA sequencing.
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Affiliation(s)
- Vincent Cattoir
- Laboratoire de Bactériologie-Virologie-Hygiène, Centre Hospitalier, Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris XII, Créteil, France
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Carothers JJ, Bruce MG, Hennessy TW, Bensler M, Morris JM, Reasonover AL, Hurlburt DA, Parkinson AJ, Coleman JM, McMahon BJ. The relationship between previous fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection. Clin Infect Dis 2006; 44:e5-8. [PMID: 17173210 DOI: 10.1086/510074] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2006] [Accepted: 09/11/2006] [Indexed: 12/19/2022] Open
Abstract
The relationship between prior fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection is unknown. Among 125 enrolled patients, 8.8% had H. pylori isolates that were resistant to levofloxacin. Levofloxacin resistance was associated with any prior fluoroquinolone use over the previous 10 years and with the total number of fluoroquinolone courses prescribed (P<.001).
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Nishizawa T, Suzuki H, Umezawa A, Muraoka H, Iwasaki E, Masaoka T, Kobayashi I, Hibi T. Rapid detection of point mutations conferring resistance to fluoroquinolone in gyrA of Helicobacter pylori by allele-specific PCR. J Clin Microbiol 2006; 45:303-5. [PMID: 17122023 PMCID: PMC1829027 DOI: 10.1128/jcm.01997-06] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori strains with reduced susceptibility to fluoroquinolones have a mutation at either codon 87 Asn or 91 Asp of the gyrA gene. A rapid test based on an allele-specific PCR (AS-PCR) was designed to detect the gyrA mutations. Clinical H. pylori isolates were obtained from the stomachs of 51 patients with H. pylori infections who showed treatment failure. The MICs of gatifloxacin (GAT) were determined by the agar dilution method. Identical genotyping results were obtained with AS-PCR and conventional PCR. The gyrA mutations of H. pylori causing reduced susceptibility to fluoroquinolones could be detected successfully by this method. A significant association was observed between the presence of mutations, as detected by AS-PCR, and the resistance of the strains to GAT. Moreover, genotyping by AS-PCR took less than 3 to 4 h. The AS-PCR method for the detection of gyrA mutations in H. pylori is useful for easy identification of fluoroquinolone-resistant strains of H. pylori.
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Affiliation(s)
- Toshihiro Nishizawa
- Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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Glocker E, Stueger HP, Kist M. Quinolone resistance in Helicobacter pylori isolates in Germany. Antimicrob Agents Chemother 2006; 51:346-9. [PMID: 17043117 PMCID: PMC1797685 DOI: 10.1128/aac.00614-06] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
We show that quinolone resistance in Helicobacter pylori has reached an alarming level in Germany. Our data suggest that the use of quinolones requires prior antimicrobial susceptibility testing, especially for isolates from patients who have already undergone previous unsuccessful eradication treatments, and also underline the further need for surveillance studies to monitor antibiotic resistance in H. pylori.
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Affiliation(s)
- Erik Glocker
- Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany
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Bogaerts P, Berhin C, Nizet H, Glupczynski Y. Prevalence and mechanisms of resistance to fluoroquinolones in Helicobacter pylori strains from patients living in Belgium. Helicobacter 2006; 11:441-5. [PMID: 16961806 DOI: 10.1111/j.1523-5378.2006.00436.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Because of the increasing resistance of Helicobacter pylori against metronidazole and clarithromycin, alternative regimens including newer fluoroquinolones have been developed. We aimed to assess the prevalence as well as the mechanisms of this resistance in clinical isolates originating from patients living in Belgium. METHODS Minimal inhibitory concentration (MIC) values of ciprofloxacin, levofloxacin, and moxifloxacin were determined by Etest method on 488 H. pylori isolates originating from patients who underwent upper gastrointestinal endoscopy at 10 different centers. Resistant strains (MIC values > 1 microg/ml) were evaluated for the presence of point mutations in the quinolone resistance-determining region (QRDR) of the gyrA by amplification and nucleotide sequence. RESULTS Eighty-two (16.8%) of the strains were found resistant to all fluoroquinolones and 70 of these were further analyzed. Homogeneous and heterogeneous resistance were observed in 55 (78.6%) and in 15 (21.4%) of the strains, respectively. QRDR sequencing revealed various mutations of the codons corresponding to Asn-87 and Asp-91 in all isolates with homogeneous resistance. However, in 12 of 15 strains displaying heterogenous resistance, mutations were only detected after subcultures of isolated colonies growing within the ellipse inhibition zone of the E-test. Amino acid substitutions in the QRDR of GyrA could not be directly related with the MIC values of the isolates. Fluoroquinolone-resistant mutants were easily selected in vitro at frequencies ranging between 10(-6) and 10(-7). Such selected mutants stably persisted after several serial passage in antibiotic-free agar. CONCLUSIONS These results suggest that H. pylori resistance to fluoroquinolones is occurring at a high frequency in the Belgian population and that it is essentially mediated through a variety of point mutations occurring in a few loci of GyrA. As a consequence, we strongly suggest to determine the susceptibility of the infecting isolates to fluoroquinolones before administration of an anti-H. pylori regimen including these agents.
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Affiliation(s)
- Pierre Bogaerts
- Laboratoire de Bactériologie, Cliniques Universitaires UCL de Mont-Godinne, Université Catholique de Louvain, B-5530 Yvoir, Belgium
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Kim N, Kim JM, Kim CH, Park YS, Lee DH, Kim JS, Jung HC, Song IS. Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea. J Clin Gastroenterol 2006; 40:683-7. [PMID: 16940878 DOI: 10.1097/00004836-200609000-00004] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
GOALS This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori isolates could be different between 2 institutions, which are located in the different areas in Korea, and to evaluate the effect of antibiotic resistance on the eradication rate of H. pylori. STUDY H. pylori were isolated from gastric mucosal biopsy specimens obtained from 113 Koreans, who did not have any eradication history. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin were examined according to the agar dilution method by 1 technician. RESULTS All of these patients were treated with the same regimen, proton pump inhibitor-amoxicillin-clarithromycin triple therapy. There was a statistical difference in resistance to metronidazole, levofloxacin, and moxifloxacin among 6 antibiotics between 2 institutions located in Seoul and Gyeonggi province. The rates of eradication were 94.2% for the clarithromycin and amoxicillin-susceptible strains, and 42.8% for the amoxicillin-susceptible and clarithromycin-resistant strains. In contrast, eradication rate was 100% for the amoxicillin-resistant strains. CONCLUSIONS These results show that there is institutional difference of antibiotic resistance of H. pylori, explaining the institutional difference of eradication rate of H. pylori. The resistance to clarithromycin seems to be an important determinant for the eradication by proton pump inhibitor triple therapy but resistance to amoxicillin does not have any effect.
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Affiliation(s)
- Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Seoul, Korea
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Miyachi H, Miki I, Aoyama N, Shirasaka D, Matsumoto Y, Toyoda M, Mitani T, Morita Y, Tamura T, Kinoshita S, Okano Y, Kumagai S, Kasuga M. Primary levofloxacin resistance and gyrA/B mutations among Helicobacter pylori in Japan. Helicobacter 2006; 11:243-9. [PMID: 16882327 DOI: 10.1111/j.1523-5378.2006.00415.x] [Citation(s) in RCA: 112] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Recent years have witnessed a decrease in the rate of Helicobacter pylori eradication due to antimicrobial resistance, clarithromycin or metronidazole resistance in particular. As one of the alternatives to the standard regimens, levofloxacin-containing therapy has been considered a promising regimen. Nevertheless, there is a little information concerning the prevalence of levofloxacin resistance and this resistance mechanism. MATERIALS AND METHODS Levofloxacin susceptibility was examined using E-test in 507 H. pylori strains clinically isolated in Japan from 2001 to 2004. Mutation patterns in the quinolone resistance-determining regions of the gyrA and gyrB genes were evaluated, performing direct sequencing of 68 levofloxacin-resistant and 50 susceptible strains. RESULTS Primary levofloxacin resistance was found in 76 (15.0%) strains. Fifty-seven (83.8%) of 68 levofloxacin-resistant strains analyzed had point mutations in gyrA at Asn-87 or Asp-91, while seven (14.0%) of 50 susceptible strains had gyrA mutations. There was a significant difference in the occurrence of gyrA mutations between levofloxacin-resistant and -susceptible strains (p < .001). In levofloxacin-resistant strains, the occurrence of gyrA mutations at Asn-87 was most common regardless of minimal inhibitory concentration levels, and that of gyrA mutations at Asp-91 tended to be associated with low-level resistance. A double gyrA mutation at Asn-87 and Asp-91 might have an additional impact. As for gyrB, three (4.4%) of 68 levofloxacin-resistant strains with no susceptible strains had mutations. CONCLUSIONS Primary levofloxacin resistance was common in Japan and primarily related to gyrA mutations at Asn-87 and Asp-91.
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Affiliation(s)
- Hideyuki Miyachi
- Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
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Sharara AI, Chaar HF, Aoun E, Abdul-Baki H, Araj GF, Kanj SS. Efficacy and safety of rabeprazole, amoxicillin, and gatifloxacin after treatment failure of initial Helicobacter pylori eradication. Helicobacter 2006; 11:231-6. [PMID: 16882325 DOI: 10.1111/j.1523-5378.2006.00416.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To evaluate the efficacy of a 7-day regimen of gatifloxacin (400 mg daily), amoxicillin (1 g twice a day), and rabeprazole (20 mg twice a day) in the secondary eradication of Helicobacter pylori infection. METHODS Eligible patients with persistent infection following one or more conventional clarithromycin-containing triple therapies were enrolled in this open-label trial. Eradication of infection was documented by (14)C-urea breath test a minimum of 4 weeks after therapy and 2 weeks off any acid suppressive therapy. Culture of H. pylori and in vitro susceptibility testing to amoxicillin, clarithromycin, and gatifloxacin was done in cases of failed eradication. RESULTS A total of 45 patients (22 females:23 males; mean age 44.5 +/- 13 years) were enrolled. Eradication occurred in 38 patients [both per-protocol (PP) and intention-to-treat analysis: 84.4%; 95% CI: 74-95%]. No significant adverse effects were reported. In vitro susceptibility testing showed no secondary resistance to gatifloxacin or amoxicillin in any of the seven nonresponders. Smoking, age, and sex were not predictors of potential eradication failure. CONCLUSIONS A 7-day regimen of gatifloxacin, rabeprazole, and amoxicillin is effective after failed eradication therapy for H. pylori and does not appear to result in secondary resistance. This combination is simple, well tolerated, and may lead to higher compliance and lower costs.
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Affiliation(s)
- Ala I Sharara
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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Nishizawa T, Suzuki H, Kurabayashi K, Masaoka T, Muraoka H, Mori M, Iwasaki E, Kobayashi I, Hibi T. Gatifloxacin resistance and mutations in gyra after unsuccessful Helicobacter pylori eradication in Japan. Antimicrob Agents Chemother 2006; 50:1538-40. [PMID: 16569878 PMCID: PMC1426923 DOI: 10.1128/aac.50.4.1538-1540.2006] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
A high resistance rate (47.9%) to gatifloxacin (GAT; 8-methoxy fluoroquinolone) in Helicobacter pylori (H. pylori) strains from 48 Japanese patients is observed after unsuccessful H. pylori eradication. A significant association between MICs for GAT equal to or above 1 microg/ml and mutations of the gyrA gene of H. pylori was demonstrated.
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Affiliation(s)
- Toshihiro Nishizawa
- Department of Internal Medicine, Keio University School of Medicine, and Department of Gastroenterology, Kitasato Institute Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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Abstract
PURPOSE OF REVIEW Inherited marrow failure syndromes (IMFSs) are rare genetic diseases with varying degrees of cytopenia. Many of the syndromes are also characterized by nonhematological manifestations and a high risk of cancer. This review summarizes recent advances in understanding the genetic background of the common IMFSs. RECENT FINDINGS Over recent years, numerous known and novel genes have been found to be associated with IMFSs. Although the functions of the proteins are largely unknown, they are postulated to play critical roles in fundamental cellular processes such as DNA repair, telomere maintenance, RNA metabolism, ribosomal biogenesis, growth-factor-signaling pathways and cell survival. For example, the telomere-related genes, DKC1 and TERC, have been identified as causes of dyskeratosis congenita. Also, homozygosity for the common cancer-associated gene, BRCA2, has been found to cause a rare subtype of Fanconi anemia. SUMMARY The knowledge of the genetics of IMFSs has started to be translated into clinical practice. The identification of IMFS-related genes provided new diagnostic tools and better classification of the various disorders. Also, these advances enabled the design of clinical trials using gene therapy and preimplantation genetic diagnosis followed by in-vitro fertilization for selection of suitable embryos for hematopoietic stem-cell transplantation.
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Affiliation(s)
- Kathryn Edwards
- Division of Infectious Diseases, CCC-5323 Medical Center North, Vanderbilt University Medical Center, Nashville, Tennessee 37223, USA.
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Kim JM, Kim JS, Kim N, Jung HC, Song IS. Distribution of fluoroquinolone MICs in Helicobacter pylori strains from Korean patients. J Antimicrob Chemother 2005; 56:965-7. [PMID: 16159928 DOI: 10.1093/jac/dki334] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The aim of this study was to assess the prevalence rate of primary fluoroquinolone resistance in Helicobacter pylori isolates from Korean patients over the past 16 years. METHODS One hundred and thirty-five strains of H. pylori (34 strains in 1987, 36 in 1994 and 65 in 2003) were isolated from antral gastric mucosal biopsy specimens. The determination of MICs for the H. pylori isolates of ciprofloxacin, levofloxacin and moxifloxacin was examined by using the serial 2-fold agar dilution method. DNA sequences of the gyrA gene in fluoroquinolone-resistant strains were determined. RESULTS The distribution of fluoroquinolone MICs (ciprofloxacin, levofloxacin and moxifloxacin) shifted to higher concentrations during 1987-2003. All of the levofloxacin- or moxifloxacin-resistant strains were resistant to ciprofloxacin. Sequence analysis in fluoroquinolone-resistant strains showed point mutation of the gyrA gene at A272G and G271A, indicating mutations of the codon Asp-91 in the fluoroquinolone-resistance-determining region of the DNA gyrase. CONCLUSIONS These results suggest that resistance to fluoroquinolones has been increasing in the Korean population and the resistance is most likely mediated through point mutation in gyrA.
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Affiliation(s)
- Jung Mogg Kim
- Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea.
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Abstract
The diagnosis of Helicobacter pylori infection continues to challenge practicing physicians around the world. In the last year, several reports from Africa tried to examine the epidemiology of H. pylori infection in nursing babies, while others investigated the association between recurrent abdominal pain symptoms and H. pylori. In the diagnostic arena, attempts were made to improve diagnostic accuracy, mainly by using a new monoclonal version of the stool antigen test, and by applying the urea breath test in smaller children. In the current report, the most important studies on H. pylori infection in children published in the last year are also reviewed.
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Affiliation(s)
- Yoram Elitsur
- Department of Pediatrics, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA.
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