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Characteristics of Antibiotic Resistance and Tolerance of Environmentally Endemic Pseudomonas aeruginosa. Antibiotics (Basel) 2022; 11:antibiotics11081120. [PMID: 36009989 PMCID: PMC9404893 DOI: 10.3390/antibiotics11081120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/15/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Antibiotic-resistant bacteria remain a serious public health threat. In order to determine the percentage of antibiotic-resistant and -tolerant Pseudomonas aeruginosa cells present and to provide a more detailed infection risk of bacteria present in the environment, an isolation method using a combination of 41 °C culture and specific primers was established to evaluate P. aeruginosa in the environment. The 50 strains were randomly selected among 110 isolated from the river. The results of antibiotic susceptibility evaluation showed that only 4% of environmental strains were classified as antibiotic-resistant, while 35.7% of clinical strains isolated in the same area were antibiotic-resistant, indicating a clear difference between environmental and clinical strains. However, the percentage of antibiotic-tolerance, an indicator of potential resistance risk for strains that have not become resistant, was 78.8% for clinical strains and 90% for environmental strains, suggesting that P. aeruginosa, a known cause of nosocomial infections, has a high rate of antibiotic-tolerance even in environmentally derived strains. It suggested that the rate of antibiotic-tolerance is not elicited by the presence or absence of antimicrobial exposure. The combination of established isolation and risk analysis methods presented in this study should provide accurate and efficient information on the risk level of P. aeruginosa in various regions and samples.
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Nhu LTT, Nguyen VL, Tran VD, Tran NA, Nguyen VT. Evaluation of the Antibiotic Resistance Rate of Helicobacter pylori in Peptic Ulcer Patients in Tien Giang Central General Hospital, Tien Giang Province, Vietnam. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.10216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND: Peptic ulcer (PU), trauma on the lining of the stomach and/or small intestine, is among the top five reasons for hospitalization in Tien Giang, a province in the South of Vietnam. Since Helicobacter pylori (HP) is one of the main causes of PU, its features, especially the antibiotic-resistant status, have critical significance in PU treatment.
AIM: This study evaluates the HP infection prevalence, HP antibiotic resistance rate, and its associations with the patients’ sociodemographic characteristics.
MATERIALS AND METHODS: A cross-sectional study was conducted on PU patients in Tien Giang province, Vietnam, from June 2020 to June 2021. The volunteers were tested for HP infection and antibiotic resistance using three methods, where appropriate, including Gram staining, CLO (urease) test, and bacterial culture method.
RESULTS: Among 368 samples, 31.5% had infected with antibiotic-resistant HP. The resistance rates to five antibiotics commonly used in HP treatment, including metronidazole, clarithromycin, tetracycline, levofloxacin, and amoxicillin, were 96.6%, 94.8%, 70.7%, 61.2%, and 53.4%, respectively. The rates of tetracycline and clarithromycin resistance were related to alcohol consumption (t-test, p < 0.05). The HP treatment history was significantly associated with the levofloxacin resistance (t-test, p < 0.05).
CONCLUSIONS: The emergence of antibiotic-resistant HP is a major public health concern in Tien Giang, Vietnam. This issue should be tackled at the national level to avoid the further spread of these multi-drug resistant HP strains.
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Chen J, Huang Y, Ding Z, Liang X, Lu H. E-Test or Agar Dilution for Metronidazole Susceptibility Testing of Helicobacter pylori: Importance of the Prevalence of Metronidazole Resistance. Front Microbiol 2022; 13:801537. [PMID: 35359733 PMCID: PMC8964178 DOI: 10.3389/fmicb.2022.801537] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/07/2022] [Indexed: 01/13/2023] Open
Abstract
Background A number of studies have shown that E-test overestimated the presence of Helicobacter pylori resistance compared to agar dilution. Objective The purpose of this study was to explore whether E-test could be an alternative for agar dilution to detect the metronidazole susceptibility of H. pylori. Method E-test and agar dilution were used to assess the susceptibility of H. pylori to metronidazole, clarithromycin, and levofloxacin in 281 clinical isolates obtained from China where the resistance was high. Cohen’s kappa analysis, McNemar’s test, and essential and categorical agreement analysis were performed for these two methods. Results Overall, the result of the E-test showed a similar prevalence of resistance rate to all antibiotics compared with agar dilution. The essential agreement of the E-test method and agar dilution in the evaluation susceptibility of H. pylori to clarithromycin and levofloxacin was moderate at 89.0 and 79.7%, respectively, but only 45.9% for metronidazole. The results shown by a categorical agreement (CA) between the E-test and agar dilution were 100% for both clarithromycin and levofloxacin. As for metronidazole, the CA was 98.7%, no major error was identified, and the rate of a very major error was 1.8%. Conclusion E-test can be an alternative method to detect the metronidazole susceptibility of H. pylori.
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Affiliation(s)
- Jinnan Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, School of Medicine, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Huang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, School of Medicine, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Zhaohui Ding
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, School of Medicine, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Liang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, School of Medicine, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Hong Lu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, School of Medicine, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
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4
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Tshibangu-Kabamba E, Yamaoka Y. Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications. Nat Rev Gastroenterol Hepatol 2021; 18:613-629. [PMID: 34002081 DOI: 10.1038/s41575-021-00449-x] [Citation(s) in RCA: 277] [Impact Index Per Article: 69.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been intensively studied and are discussed in this Review. Three profiles of resistance - single drug resistance, multidrug resistance and heteroresistance - seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens.
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Affiliation(s)
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan. .,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA.
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5
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Saracino IM, Pavoni M, Zullo A, Fiorini G, Lazzarotto T, Borghi C, Vaira D. Next Generation Sequencing for the Prediction of the Antibiotic Resistance in Helicobacter pylori: A Literature Review. Antibiotics (Basel) 2021; 10:437. [PMID: 33919811 PMCID: PMC8070836 DOI: 10.3390/antibiotics10040437] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/08/2021] [Accepted: 04/13/2021] [Indexed: 12/12/2022] Open
Abstract
Background and aims: Only a few antimicrobials are effective against H. pylori, and antibiotic resistance is an increasing problem for eradication therapies. In 2017, the World Health Organization categorized clarithromycin resistant H. pylori as a "high-priority" bacterium. Standard antimicrobial susceptibility testing can be used to prescribe appropriate therapies but is currently recommended only after the second therapeutic failure. H. pylori is, in fact, a "fastidious" microorganism; culture methods are time-consuming and technically challenging. The advent of molecular biology techniques has enabled the identification of molecular mechanisms underlying the observed phenotypic resistance to antibiotics in H. pylori. The aim of this literature review is to summarize the results of original articles published in the last ten years, regarding the use of Next Generation Sequencing, in particular of the whole genome, to predict the antibiotic resistance in H. pylori.Methods: a literature research was made on PubMed. The research was focused on II and III generation sequencing of the whole H. pylori genome. Results: Next Generation Sequencing enabled the detection of novel, rare and complex resistance mechanisms. The prediction of resistance to clarithromycin, levofloxacin and amoxicillin is accurate; for other antimicrobials, such as metronidazole, rifabutin and tetracycline, potential genetic determinants of the resistant status need further investigation.
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Affiliation(s)
- Ilaria Maria Saracino
- Microbiology Unit, Department of Specialized, Experimental, and Diagnostic Medicine, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (I.M.S.); (T.L.)
| | - Matteo Pavoni
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
| | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, ‘Nuovo Regina Margherita’ Hospital, 00153 Rome, Italy;
| | - Giulia Fiorini
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
| | - Tiziana Lazzarotto
- Microbiology Unit, Department of Specialized, Experimental, and Diagnostic Medicine, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (I.M.S.); (T.L.)
| | - Claudio Borghi
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
| | - Dino Vaira
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
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Systematic Investigation of Resistance Evolution to Common Antibiotics Reveals Conserved Collateral Responses across Common Human Pathogens. Antimicrob Agents Chemother 2020; 65:AAC.01273-20. [PMID: 33106260 PMCID: PMC7927859 DOI: 10.1128/aac.01273-20] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 10/06/2020] [Indexed: 12/22/2022] Open
Abstract
As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will be increasingly relied upon to treat infections and to lower the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic effects a specific organism’s collateral response to a wide variety of antibiotics. The results of these studies have been used to identify networks of drugs which can be used to drive resistance in a particular direction. As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will be increasingly relied upon to treat infections and to lower the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic effects a specific organism’s collateral response to a wide variety of antibiotics. The results of these studies have been used to identify networks of drugs which can be used to drive resistance in a particular direction. However, little is known about the extent of evolutionary conservation of these responses across species. We sought to address this knowledge gap by performing a systematic resistance evolution study of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae) under uniform growth conditions using five clinically relevant antibiotics with diverse modes of action. Evolved lineages were analyzed for collateral effects and the molecular mechanisms behind the observed phenotypes. Fourteen universal cross-resistance and two global collateral sensitivity relationships were found among the lineages. Genomic analyses revealed drug-dependent divergent and conserved evolutionary trajectories among the pathogens. Our findings suggest that collateral responses may be preserved across species. These findings may help extend the contribution of previous collateral network studies in the development of treatment strategies to address the problem of antibiotic resistance.
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7
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Clinical Significance of Carbapenem-Tolerant Pseudomonas aeruginosa Isolated in the Respiratory Tract. Antibiotics (Basel) 2020; 9:antibiotics9090626. [PMID: 32967210 PMCID: PMC7558279 DOI: 10.3390/antibiotics9090626] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/18/2020] [Accepted: 09/18/2020] [Indexed: 12/22/2022] Open
Abstract
We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the correlation between clinical outcomes and antibiotic tolerance. This study aims to clarify the effect of antibiotic tolerance on clinical outcomes of respiratory tract infection caused by Pseudomonas aeuginosa (P. aeruginosa). We examined a total of 63 strains isolated from sputum samples of different patients and conducted a retrospective survey with the medical records of 37 patients with imipenem-sensitive P. aeruginosa infections. Among them, we selected 15 patients with respiratory infections, and they were divided into high-tolerance minimal bactericidal concentration for adherent bacteria (MBCAD)/minimal inhibitory concentration for adherent bacteria (MICAD) ≥ 32 (n = 9) group and low-tolerance MBCAD/MICAD ≤ 16 (n = 6) group for further investigations. The findings indicated that the high-tolerance group consisted of many cases requiring hospitalization. Chest computed tomography findings showed that the disease was more extensive in the high-tolerance group compared to the low-tolerance group. Regarding the bacterial phenotypic characterization, the high-tolerance group significantly upregulated the production of the virulence factors compared to the low-tolerance group. Our study provided evidence that carbapenem tolerance level is a potent prognostic marker of P. aeruginosa infections, and carbapenem tolerance could be a potential target for new antimicrobial agents to inhibit the progression of persistent P. aeruginosa infections.
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8
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Kwon YH, Kim JY, Kim N, Park JH, Nam RH, Lee SM, Kim JW, Kim JM, Park JY, Lee DH. Specific mutations of penicillin-binding protein 1A in 77 clinically acquired amoxicillin-resistant Helicobacter pylori strains in comparison with 77 amoxicillin-susceptible strains. Helicobacter 2017; 22. [PMID: 28840971 DOI: 10.1111/hel.12437] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Amoxicillin (Amx) is one of the most important antibiotics for eradication of Helicobacter pylori (H. pylori). Main determinants of genetically stable Amx resistance are mutations in the C-terminus of penicillin-binding protein 1A (pbp1A). However, contribution of individual mutation remains unclear. METHODS 77 Amx-resistant (AmxR ) and 77 Amx-susceptible (AmxS ) H. pylori strains were isolated from gastric tissues, and DNA sequencing was performed to compare C-terminus sequences of pbp1A gene between AmxR and AmxS strains. Natural transformation of these mutated genes into amoxicillin-susceptible strains was performed. RESULTS Among many mutations in pbp1A, D479E (OR: 37.4, 95% CI: 5.53-252.49, P < .001), and T593 mutation (OR: 32.0, 95% CI: 4.04-252.86, P < .001) independently contributed to Amx resistance in H. pylori strains. In the transformation experiment, T593 mutations were identified in their transformants showing Amx resistance. However, PCR product of D479E was not inserted into recipient (ATCC 43504) resulting in transformation failure. CONCLUSION Amx resistance is associated with various substitutions in pbp1A and T593 mutation contributes to Amx resistance of H. pylori.
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Affiliation(s)
- Yong Hwan Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Ji Yeon Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Sun Min Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jung Mogg Kim
- Department of Microbiology, Hanyang University School of Medicine, Seoul, South Korea
| | | | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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9
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Shi C, Zhao X, Meng R, Liu Z, Zhang G, Guo N. Synergistic antimicrobial effects of nisin and p-Anisaldehyde on Staphylococcus aureus in pasteurized milk. Lebensm Wiss Technol 2017. [DOI: 10.1016/j.lwt.2017.05.056] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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10
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Murakami K, Ono T, Noma Y, Minase I, Amoh T, Irie Y, Hirota K, Miyake Y. Explorative gene analysis of antibiotic tolerance-related genes in adherent and biofilm cells of Pseudomonas aeruginosa. J Infect Chemother 2017; 23:271-277. [PMID: 28274550 DOI: 10.1016/j.jiac.2017.01.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 01/11/2017] [Accepted: 01/17/2017] [Indexed: 11/25/2022]
Abstract
BACKGROUND Antibiotic tolerance has attracted worldwide attention, as it leads to chronic, refractory, and persistent infections that are difficult to control. Bacterial biofilms are well known to be more tolerant to antibiotics compared to planktonic bacteria. We previously revealed that adherent bacteria on a solid surface also exhibited tolerance to antibiotics before forming a biofilm. However, little is known about the mechanisms of antibiotic tolerance for adherent or biofilm cells. OBJECTIVES We investigated the mechanisms of antibiotic tolerance in the biofilm life cycle using adherent and biofilm cells, and evaluated the possibility that common mechanisms operate at each stage. METHODS We constructed transposon mutants of Pseudomonas aeruginosa PAO1 and screened for low-tolerant mutants with two different methods, using adherent cells and biofilm cells. RESULTS Fourteen and nine mutants exhibiting low antibiotic tolerance were detected in the adherent cells and biofilm cells, and 14 and 7 candidate genes linked to this tolerance were identified by sequencing, respectively. Eight of the 14 genes related to the antibiotic tolerance of the adherent cells were involved in biofilm formation. Two of the seven genes related to the antibiotic tolerance of biofilm cells participated in the antibiotic tolerance of adherent cells. CONCLUSIONS The antibiotic tolerance of adherent cells and biofilm formation appear to be under the same regulation mechanism to promote survival in the presence of antibiotics. Antibiotic tolerance shows a complex regulation mechanism at each stage of biofilm formation.
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Affiliation(s)
- Keiji Murakami
- Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
| | - Tsuneko Ono
- Department of Molecular Microbiology, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
| | - Yasuki Noma
- Department of Molecular Microbiology, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
| | - Issei Minase
- Department of Molecular Microbiology, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
| | - Takashi Amoh
- Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
| | - Yasuhiko Irie
- Department of Biology, University of Dayton, Dayton, OH, USA
| | - Katsuhiko Hirota
- Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
| | - Yoichiro Miyake
- Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan
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Miftahussurur M, Cruz M, Subsomwong P, Jiménez Abreu JA, Hosking C, Nagashima H, Akada J, Yamaoka Y. Clarithromycin-Based Triple Therapy is Still Useful as an Initial Treatment for Helicobacter pylori Infection in the Dominican Republic. Am J Trop Med Hyg 2017; 96:1050-1059. [PMID: 28193745 DOI: 10.4269/ajtmh.16-0729] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
AbstractHelicobacter pylori antibiotic susceptibility in the Dominican Republic has not been monitored. We assessed H. pylori antibiotic susceptibility in the Dominican Republic, and analyzed H. pylori mutations associated with antibiotic resistance. We recruited 158 dyspeptic patients in Santo Domingo and used agar dilution to test susceptibility to five antibiotics. Polymerase chain reaction-based sequencing was used to assess gyrA, gyrB, rdxA, frxA, and 23S rRNA mutations; next-generation sequencing was used to identify other metronidazole resistance-associated genes. Among 64 H. pylori strains isolated, we identified two (3.1%), one (1.6%), and no strains with clarithromycin, amoxicillin, and tetracycline resistance, respectively. Moreover, high frequency of metronidazole resistance (53/64, 82.8%) was observed, whereas levofloxacin resistance is emerging (23/64, 35.9%). We identified many rdxA and frxA mutations in metronidazole-resistant strains, but no synergistic effect was apparent. We revealed novel mutations in dppA, dppB, fdxA, and fdxB, irrespective of rdxA and frxA mutations. Novel mutations at Ser-14 of trx1 and Arg-221 of dapF were associated with different levels of metronidazole resistance. Most levofloxacin-resistant strains had a substitution at Asn-87 of gyrA, including the strain with the highest levofloxacin resistance, whereas only three substitutions were found at Ser-479 of gyrB with no synergistic effect. Besides the 23S rRNA A2142G mutation, we observed another mutation at T1958G in both clarithromycin-resistant strains. We confirmed high metronidazole and levofloxacin resistance associated with genetic mutations in the Dominican Republic. However, prevalence of clarithromycin resistance was low, suggesting that standard clarithromycin-based triple therapy remains useful as initial treatment of H. pylori infection.
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Affiliation(s)
- Muhammad Miftahussurur
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas.,Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital-Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Modesto Cruz
- Institute of Microbiology and Parasitology, Faculty of Science, Autonomous University of Santo Domingo, Santo Domingo, Dominican Republic.,Department of Biomedical Research, National Institute of Medicine and Diagnostic Imaging, Santo Domingo, Dominican Republic
| | - Phawinee Subsomwong
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - José A Jiménez Abreu
- Dominican-Japanese Digestive Disease Center, Dr. Luis E. Aybar Health and Hygiene City, Santo Domingo, Dominican Republic
| | - Celso Hosking
- Institute of Microbiology and Parasitology, Faculty of Science, Autonomous University of Santo Domingo, Santo Domingo, Dominican Republic
| | - Hiroyuki Nagashima
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Junko Akada
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan.,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas
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12
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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: 101] [Impact Index Per Article: 11.2] [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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13
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Lee DS, Eom SH, Kim YM, Kim HS, Yim MJ, Lee SH, Kim DH, Je JY. Antibacterial and synergic effects of gallic acid-grafted-chitosan with β-lactams against methicillin-resistant Staphylococcus aureus (MRSA). Can J Microbiol 2014; 60:629-38. [DOI: 10.1139/cjm-2014-0286] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is spreading worldwide, emphasizing the need to search for new antibiotics. The anti-MRSA activities of gallic acid-grafted-chitosans (GA-g-chitosans) were investigated against 2 MRSA standards and 10 MRSA clinical isolates by determining the minimum inhibitory concentrations (MICs). GA-g-chitosan (I), which has the highest gallic acid content, exhibited the strongest anti-MRSA activities, with MICs of 32–64 μg/mL. A time-kill investigation revealed that GA-g-chitosan (I) exhibited a bactericidal effect at twice the MIC, also demonstrating good thermal and pH stability. Investigation of cell envelope integrity showed the release of intracellular components with an increasing absorbance value at 260 nm, indicating cell envelope damage caused by the GA-g-chitosan (I), which was further confirmed by transmission electron microscopy. When GA-g-chitosans were combined with β-lactams, including ampicillin and penicillin, synergistic effects were observed on the 2 standard MRSA strains and on the 10 clinical isolates, with fractional inhibitory indices ranging from 0.125 to 0.625. In the time-kill dynamic confirmation test, synergistic bactericidal effects were observed for the combinations of GA-g-chitosans with β-lactams, and over 4.0 log CFU/mL reductions were observed after 24 h when combination treatment was used. These results may prove GA-g-chitosans to be a potent agent when combined with ampicillin and penicillin for the elimination of MRSA.
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Affiliation(s)
- Dae-Sung Lee
- Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea
| | - Sung-Hwan Eom
- Division of Platform Technology Research, Korea Food Research Institute, Sungnam 463-749, Republic of Korea
| | - Young-Mog Kim
- Department of Food Science and Technology, Pukyong National University, Busan 608-737, Republic of Korea
| | - Hye Seon Kim
- Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea
| | - Mi-Jin Yim
- Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea
| | - Sang-Hoon Lee
- Food Resource Research Center, Korea Food Research Institute, Sungnam 463-749, Republic of Korea
- University of Science and Technology, Daejeon 305-350, Republic of Korea
| | - Do-Hyung Kim
- Department of Aquatic Life Medicine, Pukyong National University, Busan 608-737, Republic of Korea
| | - Jae-Young Je
- Department of Marine-Bio Convergence Science, Pukyong National University, Busan 608-737, Republic of Korea
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Yang JC, Lu CW, Lin CJ. Treatment of Helicobacter pylori infection: current status and future concepts. World J Gastroenterol 2014; 20:5283-93. [PMID: 24833858 PMCID: PMC4017043 DOI: 10.3748/wjg.v20.i18.5283] [Citation(s) in RCA: 152] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/28/2013] [Accepted: 01/19/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly associated with the occurrence of gastrointestinal diseases, including gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma. Although alternative therapies, including phytomedicines and probiotics, have been used to improve eradication, current treatment still relies on a combination of antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, and levofloxacin, and antisecretory agents, such as proton pump inhibitors (PPIs). A standard triple therapy consisting of a PPI and two antibiotics (clarithromycin and amoxicillin/metronidazole) is widely used as the first-line regimen for treatment of infection, but the increased resistance of H. pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy. Alternatively, levofloxacin-based triple therapy can be used as rescue therapy for H. pylori infection after failure of first-line therapy. The increase in resistance to antibiotics, including levofloxacin, may limit the applicability of such regimens. However, since resistance of H. pylori to amoxicillin is generally low, an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy. In addition, the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H. pylori infection, though its efficacy needs to be verified in clinical studies.
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Efficacy and pharmacological mechanism of pronase-enhanced low-dose antibiotics for Helicobacter pylori eradication. Antimicrob Agents Chemother 2014; 58:3348-53. [PMID: 24687504 DOI: 10.1128/aac.02319-13] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
This study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian gerbils infected with H. pylori received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of H. pylori. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (P = 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in H. pylori eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on H. pylori collectively. Thus, pronase may enhance the level of antibiotics for eradication of H. pylori in the clinic.
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Kim BJ, Kim JG. Substitutions in penicillin-binding protein 1 in amoxicillin-resistant Helicobacter pylori strains isolated from Korean patients. Gut Liver 2013; 7:655-60. [PMID: 24312705 PMCID: PMC3848547 DOI: 10.5009/gnl.2013.7.6.655] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Revised: 02/05/2013] [Accepted: 02/05/2013] [Indexed: 12/11/2022] Open
Abstract
Background/Aims A worldwide increase in amoxicillin resistance in Helicobacter pylori is having an adverse effect on eradication therapy. In this study, we investigated the mechanism of the amoxicillin resistance of H. pylori in terms of amino acid substitutions in penicillin-binding protein 1 (PBP1). Methods In total, 150 H. pylori strains were isolated from 144 patients with chronic gastritis, peptic ulcers, or stomach cancer. The minimum inhibitory concentrations (MICs) of the strains were determined with a serial 2-fold agar dilution method. The resistance breakpoint for amoxicillin was defined as >0.5 µg/mL. Results Nine of 150 H. pylori strains showed amoxicillin resistance (6%). The MIC values of the resistant strains ranged from 1 to 4 µg/mL. A PBP1 sequence analysis of the resistant strains revealed multiple amino acid substitutions: Val16→Ile, Val45→Ile, Ser414→Arg, Asn562→Tyr, Thr593→Ala, Gly595→Ser, and Ala599→Thr. The natural transformation of these mutated genes into amoxicillin-sensitive strains was performed in two separate pbp1 gene segments. A moderate increase in the amoxicillin MIC was observed in the segment that contained the penicillin-binding motif of the C-terminal portion, the transpeptidase domain. Conclusions pbp1 mutation affects the amoxicillin resistance of H. pylori through the transfer of the penicillin-binding motif.
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Affiliation(s)
- Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
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High Helicobacter pylori resistance to metronidazole and clarithromycin in Brazilian children and adolescents. J Pediatr Gastroenterol Nutr 2013; 56:645-8. [PMID: 23403439 DOI: 10.1097/mpg.0b013e31828b3669] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE The aim of the present study was to assess the primary and secondary resistance of Helicobacter pylori strains to clarithromycin, amoxicillin, furazolidone, tetracycline, and metronidazole, the conventional antibiotics presently used in Brazilian children and adolescents. METHODS Seventy-seven consecutive H pylori strains, 71 of 77 strains obtained from patients without previous eradication treatment for H pylori infection, and 6 strains from patients in whom previous eradication treatment had failed. RESULTS Global rate of resistance was 49.3% (38/77): 40% of strains were resistant to metronidazole, 19.5% to clarithromycin, and 10.4% to amoxicillin. All of the tested H pylori strains were susceptible to furazolidone and tetracycline. Multiple resistance were detected in 18.2% (14/77 patients) of the strains: 6 of 14 (43%) simultaneously resistant to clarithromycin and metronidazole; 5 of 14 (36%) to amoxicillin and metronidazole; 2 of 14 (14%) to amoxicillin, clarithromycin, and metronidazole; and 1 of 14 (7%) to clarithromycin and amoxicillin. CONCLUSIONS The high resistance rate to metronidazole and clarithromycin observed in clinical H pylori isolates can exclude these antimicrobials in empirical eradication treatment in Brazil. Otherwise, furazolidone and tetracycline presented no resistance. Properly assessing the risks and benefits, these 2 antimicrobials and their derivatives could be used in empirical eradication schedules, both associated with amoxicillin, which showed a low resistance rate despite its wide use in pediatric patients.
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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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TRANG VT, SON VH, THANH LX, SARTER S, SHIMAMURA T, UKED H, TAKEUCHI H. Functional Properties of Maillard Reaction Products in Food: Antimicrobial Activity of Aminoreductone against Pathogenic Bacteria. FOOD SCIENCE AND TECHNOLOGY RESEARCH 2013. [DOI: 10.3136/fstr.19.833] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Sun HF, Li XM, Meng L, Cui CM, Gao SS, Li CS, Huang CG, Wang BG. Asperolides A-C, tetranorlabdane diterpenoids from the marine alga-derived endophytic fungus Aspergillus wentii EN-48. JOURNAL OF NATURAL PRODUCTS 2012; 75:148-52. [PMID: 22283451 DOI: 10.1021/np2006742] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Bioassay-guided fractionation of the culture extract of Aspergillus wentii EN-48, an endophytic fungus isolated from an unidentified marine brown algal species of the genus Sargassum, led to the isolation of three new tetranorlabdane diterpenoids, asperolides A-C (1-3), and five related derivatives (4-8). The structures of these compounds were established on the basis of spectroscopic interpretation, and compound 1 was confirmed by X-ray crystallographic analysis. The absolute configuration of 1 was determined by application of the modified Mosher's method. An X-ray structure for wentilactone B (6) is also reported. Compounds 1-8 were evaluated for cytotoxic and antibacterial activities.
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Affiliation(s)
- Hao-Fen Sun
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Nanhai Road 7, Qingdao 266071, People's Republic of China
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Helicobacter pylori eradication by sitafloxacin-lansoprazole combination and sitafloxacin pharmacokinetics in Mongolian gerbils and its in vitro activity and resistance development. Antimicrob Agents Chemother 2011; 55:4261-6. [PMID: 21730117 DOI: 10.1128/aac.01105-10] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A total of 293 strains of Helicobacter pylori, including strains resistant to levofloxacin, clarithromycin, metronidazole, or amoxicillin, were examined for in vitro susceptibility to 10 antimicrobial agents. Among these agents, sitafloxacin (a fluoroquinolone) showed the greatest activity (MIC(90), 0.06 μg/ml), with high bactericidal activity and synergy in sitafloxacin-lansoprazole (a proton pump inhibitor) combination. In a Mongolian gerbil model with a H. pylori ATCC 43504 challenge, marked eradication effects were observed at ≥1 mg/kg for sitafloxacin, ≥10 mg/kg for levofloxacin, and ≥10 mg/kg for lansoprazole, reflecting MIC levels for each agent (0.008, 0.25, and 2 μg/ml, respectively). The therapeutic rates were 83.3% for the sitafloxacin (0.3 mg/kg)-lansoprazole (2.5 mg/kg) combination and 0% for either sitafloxacin or lansoprazole alone. The maximum serum concentration (C(max)) of sitafloxacin was 0.080 ± 0.054 μg/ml at 30 min, when orally administered at 1 mg/kg. The simultaneous administration of lansoprazole resulted in no difference. In the resistance development assay, MICs of levofloxacin increased 64- to 256-fold with gyrA mutations (Ala88Pro and Asn87Lys), while MICs of sitafloxacin only up to 16-fold with the Asn87Lys mutation. The data suggest that sitafloxacin exhibited superior anti-H. pylori activity with low rates of resistance development in vitro and that, reflecting high in vitro activities, sitafloxacin-lansoprazole combination exhibited strong therapeutic effects in Mongolian gerbils with a C(max) of sitafloxacin that was 10-fold higher than the MIC value at a 1-mg/kg administration.
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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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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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Jin X, Wang X, Ren C, Miao Y, Yi L. Theoretical study on interactions of β-cyclodextrin with Helicobacter pylori eradicating agent (TG44). J Mol Model 2010; 17:913-20. [PMID: 20607331 DOI: 10.1007/s00894-010-0781-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2010] [Accepted: 06/11/2010] [Indexed: 11/29/2022]
Abstract
The inclusion complex of β-cyclodextrin (β-CD) and 4-methylbenzyl-4'-[trans-4- (guanidinomethyl)cylohexylcarbonyloxy]-biphenyl-4-carboxlylate monohydrochloride (TG44) had been investigated by using densify functional theory (DFT) and PM3 semiempirical method. The results indicate that the β-CD includes predominantly the biphenyl moiety of TG44, and the inclusion complex formed by TG44 entering into the cavity of β-CD from its narrow side (the primary hydroxyl group side) is more stable than that formed by TG44 entering into the cavity of β-CD from its wide side (the secondary hydroxyl group side). The negative enthalpy changes calculated from the statistical thermodynamic calculations at 1 atm and 298.15 K suggest that the inclusion complexes are favored enthalpy-driven processes. The molecular modeling results are in good agreement with the experiment for 2D (1)H-(13)C H HETCOR spectroscopic and H-NMR spectroscopic observations.
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Affiliation(s)
- Xin Jin
- Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, Hunan 411105, People's Republic of China
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Tseng YS, Wu DC, Chang CY, Kuo CH, Yang YC, Jan CM, Su YC, Kuo FC, Chang LL. Amoxicillin resistance with beta-lactamase production in Helicobacter pylori. Eur J Clin Invest 2009; 39:807-12. [PMID: 19614952 DOI: 10.1111/j.1365-2362.2009.02166.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Amoxicillin-resistant Helicobacter pylori with minimal inhibitory concentration (MIC) >or= 256 mg L(-1) was isolated from a gastritis patient. The aims were to investigate the mechanism of high-level amoxicillin resistance in H. pylori. MATERIALS AND METHODS The beta-lactamase production was determined by means of nitrocefin sticks and the presence of gene encoding the beta-lactam antibiotic resistance enzyme TEM beta-lactamase was analysed by polymerase chain reaction (PCR), sequencing and dot-blot hybridization. Sequencing analysis of pbp1A gene was performed and amoxicillin-susceptible isolate was transformed with pbp1A PCR products from the resistant isolate. The expression of hefC efflux system was analysed using real-time quantitative PCR. RESULTS Activity of beta-lactamase was detected. Sequence analysis showed that the PCR product derived from H. pylori 3778 was identical to the bla(TEM-1) (GenBank accession EU726527). Dot-blot hybridization confirmed the presence of beta-lactamase gene bla(TEM-1.) By transformation of PCR product of mutated pbp1A gene from H. pylori 3778 into amoxicillin-susceptible strain showed that substitutions in Thr(556)-->Ser, Lys(648)-->Gln, Arg(649)-->Lys and Arg(656)-->Pro contribute to low-level amoxicillin resistance. The MIC of amoxicillin for the transformants was 0.75 mg L(-1). Over-expression of hefC was not found. CONCLUSIONS High-level amoxicillin resistance is associated with beta-lactamase production in H. pylori. Low-level amoxicillin resistance is linked to a point mutation on pbp1A. Because H. pylori can exchange DNA through natural transformation, spreading of bla(TEM-1) amoxicillin resistance gene among H. pylori is a potential threat when treating H. pylori infection.
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Affiliation(s)
- Y-S Tseng
- Department of Microbiology, Kaohsiung Medical University, Kaohsiung, Taiwan
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Anzai K, Mizoguchi JI, Yanagi T, Hirayama F, Arima H, Uekama K. Improvement of Dissolution Properties of a New Helicobacter pylori Eradicating Agent (TG44) by Inclusion Complexation with .BETA.-Cyclodextrin. Chem Pharm Bull (Tokyo) 2007; 55:1466-70. [DOI: 10.1248/cpb.55.1466] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Kinsei Anzai
- Nagase ChemteX Corporation, Kobe Product Development Center
| | | | | | | | - Hidetoshi Arima
- Graduate School of Pharmaceutical Sciences, Kumamoto University
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Ibrahim M, Khan AA, Tiwari SK, Habeeb MA, Khaja MN, Habibullah CM. Antimicrobial activity of Sapindus mukorossi and Rheum emodi extracts against H pylori: In vitro and in vivo studies. World J Gastroenterol 2006; 12:7136-42. [PMID: 17131475 PMCID: PMC4087774 DOI: 10.3748/wjg.v12.i44.7136] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the antibacterial activity of Sapindus mukorossi (S. mukorossi) and Rheum emodi (R. emodi).
METHODS: Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzene, chloroform and ethanol and were concentrated in vacuum. The disk diffusion method was used for in vitro studies and in vivo studies were performed on male Wister rats. Thirty resistant clinical isolates of H pylori, as determined by their antibiotic sensitivity patterns by E-test, along with two Gram +ve (S. aureus, B. subtilis) and two Gram -ve (E. coli, P. vugaris) organisms were screened for their susceptibility patterns against these extracts.
RESULTS: In our screening, all 30 resistant isolates and the other four organisms (two Gram +ve S. aureus, B. subtilis and two Gram -ve, E. coli, P. vugaris) were sensitive to the test compounds. It was found that ethanol and chloroform extracts of S. mukorossi and ethanol and benzene extracts of R. emodi inhibited H pylori at very low concentrations. In the in vitro study, the isolates showed a considerable zone of inhibition at very low concentrations (10 μg/mL) for both the extracts. In the in vivo study, the H pylori infection was cleared with minimal doses of extracts of S. mukorossi (2.5 mg/mL) and R. emodi (3.0 mg/mL) given orally for seven days.
CONCLUSION: We can conclude from this study that the extracts of S. mukorossi and R. emodi inhibited the growth of pylori in vitro and, in in vivo studies, the H pylori infection cleared within seven days at very low concentrations. We also found that H pylori did not acquire resistance against these herbal extracts even after 10 consecutive passages.
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Affiliation(s)
- Mohammed Ibrahim
- Centre for Liver Research and Diagnostics, Deccan college of Medical Sciences and Allied Hospitals, Kanchanbagh, Hyderabad 500064, India.
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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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Takeuchi H, Nakazawa T, Okamoto T, Shirai M, Kimoto M, Nishioka M, Con SA, Morimoto N, Sugiura T. Cell elongation and cell death of helicobacter pylori is modulated by the disruption of cdrA (cell division-related gene A). Microbiol Immunol 2006; 50:487-97. [PMID: 16858140 DOI: 10.1111/j.1348-0421.2006.tb03819.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The cell division-related gene A (cdrA) of Helicobacter pylori is dispensable in vivo and unique in having a repressive role on cell division and long-term survival. To clarify its role, comparisons of the wildtype HPK5 and isogenic cdrA-disrupted mutant HPKT510 were examined by ultrastructural morphology, PBP profiles, and susceptibility to beta-lactam antibiotics during long-term cultivation. Ultrastructural analyses revealed that the shorter rods of HPKT510 had a slightly wider periplasmic space between the inner and the outer membrane than those of HPK5. Cell division of HPKT510 cells was complete even under high-salt conditions in which HPK5 cells became filamentous due to inhibition of division. The filamentous HPK5 cells constructed an inner membrane without a cell wall at the presumed division site. After 4 days of cultivation (the late stationary phase), most of the HPK5 cells turned into ghosts and aggregates, while some of the HPKT510 cells remained as curved rods, which coincided with the results of cell viability. HPKT510 cells became resistant to ampicillin killing compared to HPK5 cells, although their minimum inhibitory concentrations (MICs) and PBP profiles were not significantly different. These results suggest that the cdrA product represses cell division via inhibiting cell wall synthesis at division site. During infection in both mice and humans, inactivation of cdrA eventually gains biological aspects such as increased viability, long-term survival and tolerance to antibiotics and high-salt condition, which might enhance a persistent infection.
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Affiliation(s)
- Hiroaki Takeuchi
- Department of Clinical Laboratory Medicine, Kochi University School of Medicine, Nankoku, Kochi, Japan.
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Mirbagheri SA, Hasibi M, Abouzari M, Rashidi A. Triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H pylori eradication: A comparative three-armed randomized clinical trial. World J Gastroenterol 2006; 12:4888-91. [PMID: 16937475 PMCID: PMC4087627 DOI: 10.3748/wjg.v12.i30.4888] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the effectiveness of triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H pylori eradication in a comparative three-armed randomized clinical trial.
METHODS: A total of 360 H pylori-positive patients suffering from dyspepsia and aging 24-79 years with a median age of 42 years were enrolled in the study and randomly allocated into the following three groups: group A (n = 120) received a standard 1-wk triple therapy (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 500 mg clarithromycin b.i.d.); group B (n = 120) received a 10-d standard quadruple therapy (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 240 mg colloidal bismuth subcitrate b.i.d., and 500 mg metronidazole b.i.d.); group C (n = 120) received the new protocol, i.e. 375 mg sultamicillin (225 mg ampicillin plus 150 mg sulbactam) b.i.d. (before breakfast and dinner), instead of amoxicillin in the standard quadruple therapy for the same duration. Chi-square test with the consideration of P < 0.05 as significant was used to compare the eradication rates by intention-to-treat and per-protocol analyses in the three groups.
RESULTS: The per-protocol eradication rate was 91.81% (101 patients from a total of 110) in group A, 85.84% (97 patients from a total of 113) in group B, and 92.85% (104 patients from a total of 112) in group C. The intention-to-treat eradication rate was 84.17% in group A, 80.83% in group B, and 86.67% in group C. The new protocol yielded the highest eradication rates by both per-protocol and intention-to-treat analyses followed by the standard triple and quadruple regimens, respectively. However, the differences were not statistically significant between the three groups.
CONCLUSION: The results of this study provide further support for the equivalence of triple and quadruple therapies in terms of effectiveness, compliance and side-effect profile when administered as first-line treatment for H pylori infection. Moreover, the new protocol using ampicillin-sulbactam instead of amoxicillin in the quadruple regimen is a suitable first-line alternative to be used in regions with amoxicillin-resistant H pylori strains.
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Gerrits MM, Godoy APO, Kuipers EJ, Ribeiro ML, Stoof J, Mendonça S, van Vliet AHM, Pedrazzoli J, Kusters JG. Multiple mutations in or adjacent to the conserved penicillin-binding protein motifs of the penicillin-binding protein 1A confer amoxicillin resistance to Helicobacter pylori. Helicobacter 2006; 11:181-7. [PMID: 16684266 DOI: 10.1111/j.1523-5378.2006.00398.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Amoxicillin-based therapies are highly effective for the treatment of Helicobacter pylori infections, but the efficacy may decrease as the incidence of amoxicillin resistance is increasing. So far, the molecular mechanism underlying stable amoxicillin resistance has only been identified for a few naturally occurring amoxicillin-resistant (Amx) H. pylori isolates, and is mediated by mutations in penicillin-binding protein 1A (PBP1A). In this study the molecular mechanism underlying amoxicillin resistance of seven additional Amx H. pylori isolates has been established. METHODS H. pylori strain 26695 (minimal inhibitory concentration (MIC) 0.125 mg/l) was naturally transformed with total DNA and pbp1A polymerase chain reaction (PCR) products from the seven Amx H. pylori isolates, and the MIC of amoxicillin and pbp1A gene sequence of the obtained Amx transformants were determined. RESULTS Replacement of the wild-type pbp1A gene of H. pylori reference strain 26695 by the pbp1A gene of the Amx H. pylori isolates resulted in an increased MIC (0.5-1.0 mg/l). Sequence analysis of the smallest PBP1A fragments able to transfer the resistance indicated that several amino acid substitutions in or adjacent to the second (SKN402-404) and third (KTG555-557) conserved penicillin-binding protein motifs (PBP-motifs) mediate amoxicillin resistance in H. pylori. This was confirmed by site-directed mutagenesis using oligonucleotides that contained defined mutations in or adjacent to these PBP-motifs. CONCLUSION In naturally occurring Amx H. pylori isolates, amoxicillin resistance is mediated by various mutational changes located in or adjacent to the second and third PBP-motifs of the PBP1A. Although we cannot exclude the role of the other genes in amoxicillin resistance, it is likely that multiple mutational changes in the PBP1A gene are the predominant cause of amoxicillin resistance in H. pylori. The findings of this study currently preclude the rapid detection of amoxicillin resistance in H. pylori by molecular tests.
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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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Anzai K, Kono H, Mizoguchi JI, Yanagi T, Hirayama F, Arima H, Uekama K. Two-dimensional 13C–1H heteronuclear correlation NMR spectroscopic studies for the inclusion complex of cyclomaltoheptaose (β-cyclodextrin) with a new Helicobacter pylori eradicating agent (TG44) in the amorphous state. Carbohydr Res 2006; 341:499-506. [PMID: 16427035 DOI: 10.1016/j.carres.2005.12.008] [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] [Received: 11/17/2005] [Revised: 12/20/2005] [Accepted: 12/22/2005] [Indexed: 10/25/2022]
Abstract
The interaction of a newly developed Helicobacter pylori eradicating agent (TG44, 4-methylbenzyl-4'-[trans-4-(guanidinomethyl)cyclohexylcarbonyloxy]-biphenyl-4-carboxlylate monohydrochloride) with cyclomaltoheptaose (beta-cyclodextrin, beta-CyD) in the solid state was studied by high-speed frequency-switched Lee-Goldburg (FSLG) (13)C-(1)H heteronuclear correlation (HETCOR) NMR experiments. The TG44/beta-CyD solid complex in a 1:1 stoichiometry was prepared by the grinding method. Powder X-ray diffractometry confirmed that the complex is in an amorphous state. The solid-state (13)C signals of TG44 and beta-CyD were significantly broadened by the complexation. As the temperature increased, the (13)C signals of the aromatic moieties of TG44 were insignificantly influenced, whereas those of the cyclohexyl moiety became sharper. The T1(rho) H values of the aromatic moieties of TG44 were almost the same as those of the beta-CyD carbons, whereas those of other TG44 carbons gave much smaller values. The (13)C-(1)H HETCOR spectra gave the intermolecular correlation peaks between the aromatic carbons of TG44 and the beta-CyD protons or between the biphenyl protons of TG44 and the beta-CyD carbons, when measured using longer contact times (500 and 1500mus). On the basis of these solid NMR spectroscopic data together with aqueous NMR data, we assume that beta-CyD includes predominantly the biphenyl moiety of TG44 in the solid state. (13)C-(1)H HETCOR spectroscopy is particularly useful for the determination of inclusion modes of the complexes that occurring in an amorphous form.
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Affiliation(s)
- Kinsei Anzai
- Nagase ChemteX Corporation, Kobe Product Development Center, 2-2-3 Murotani, Nishi-ku, Kobe, Hyogo 651-2241, Japan
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Antos D, Schneider-Brachert W, Bästlein E, Hänel C, Haferland C, Buchner M, Meier E, Trump F, Stolte M, Lehn N, Bayerdörffer E. 7-day triple therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and high-dose esomeprazole in patients with known antimicrobial sensitivity. Helicobacter 2006; 11:39-45. [PMID: 16423088 DOI: 10.1111/j.0083-8703.2006.00375.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: 12/23/2022]
Abstract
BACKGROUND AND AIMS Failed primary anti-Helicobacter pylori therapy results in a high rate of antimicrobial resistance. This necessitates a search for new regimens to cure H. pylori infection. The aim of this study was to evaluate the efficacy and tolerability of a new levofloxacin-containing 7-day triple therapy and to compare it with that of standard French triple therapy in patients with known H. pylori susceptibility to MET (metronidazole) and CLA (clarithromycin). PATIENTS AND METHODS Sixty-one patients with documented antibiotic sensitivity (E-test) and an indication for anti-H. pylori treatment based on the Maastricht Consensus 2/2000 guidelines were randomized to receive either esomeprazole 2 x 40 mg, levofloxacin 2 x 500 mg, and amoxicillin 2 x 1 g for 7 days (ELA, n = 30), or esomeprazole 2 x 20 mg, clarithromycin 2 x 500 mg, and amoxicillin 2 x 1 g for 7 days (ECA, n = 31). A cure check was performed 4-6 weeks after conclusion of therapy. RESULTS Sixty-one patients were randomized to the two treatment groups. Twenty-eight of 30 patients of the ELA group were available for per-protocol (PP) analysis, of whom 26 (92.9% CI: 76-99%; intention-to-treat [ITT] analysis 86.7% CI: 68-96%) became H. pylori negative compared with 26 of the 31 patients of the ECA group (83.9%, CI: 66-93% both PP and ITT analyses). Five patients of the ELA group showed CLA resistance, three of whom also showed MET resistance, and all five were treated successfully. Two patients with levofloxacin-resistant strains, one in each group, were cured. Both regimens were generally well tolerated with minor adverse events being seen in 15 patients (51.7%) of the ELA group and in 13 (40.6%) of the ECA group. None of the patients discontinued treatment prematurely due to adverse events. CONCLUSION The data of this pilot study suggest a better than 80% efficacy of the new 7-day levofloxacin triple therapy, which is within the range of the French triple therapy in patients with MET- and CLA-susceptible strains. The data suggest that the new levofloxacin triple therapy may also be an option in patients with MET- and CLA-resistant H. pylori strains.
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Affiliation(s)
- David Antos
- Clinic for Pediatric Diseases, Ludwigs-Maximilians-University, Munich, Germany
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Lopes AI, Oleastro M, Palha A, Fernandes A, Monteiro L. Antibiotic-resistant Helicobacter pylori strains in Portuguese children. Pediatr Infect Dis J 2005; 24:404-9. [PMID: 15876938 DOI: 10.1097/01.inf.0000160941.65324.6b] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Data concerning the effectiveness of Helicobacter pylori eradication regimens based in antibiotic susceptibility testing are scanty in children. AIMS To identify the prevalence of antibiotic resistance in H. pylori strains isolated from Portuguese children in 1999-2003; to evaluate eradication rate after antibiotic susceptibility testing-based treatment; and to identify factors associated with resistance and eradication outcome. METHODS Included were 109 children with a gastric biopsy culture positive for H. pylori. First treatment (amoxicillin, omeprazole and clarithromycin or metronidazole) was guided by susceptibility testing (E test), and eradication was assessed by [C]urea breath test. RESULTS Strains were susceptible to amoxicillin and tetracycline; 39.4% were resistant to clarithromycin, 16.5% to metronidazole and 4.5% to ciprofloxacin. No significant association was found between resistance and sex, age, clinical status, gastritis scores, H. pylori density scores and genotype. Clarithromycin resistance was significantly associated with European origin [odds ratio (OR), 3.9], previous H. pylori empiric therapy (OR 2.8) and amoxicillin minimal inhibitory concentration, > or =0.016 (OR 6.0). Eradication rate after susceptibility-based treatment was 74.7% (59 of 79; 95% confidence interval, 65.9-82.9), and a significant association was found between eradication failure and presence of resistance to 1 or more antibiotics (P < 0.05). CONCLUSIONS The prevalence of H. pylori antibiotic resistance was high in the studied population. The modest therapeutic success of clarithromycin and metronidazole susceptibility-based regimens suggests that in addition to resistance, other factors may be involved. The need of susceptibility-based treatment studies in children and of antimicrobial resistance surveillance in high prevalence areas for H. pylori are emphasized.
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Affiliation(s)
- Ana Isabel Lopes
- Unit of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, INSA, Lisbon, Portugal.
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Watanabe K, Tanaka A, Imase K, Tokunaga K, Sugano H, Kai A, Ishida H, Itoh T, Takahashi S. Amoxicillin resistance in Helicobacter pylori: studies from Tokyo, Japan from 1985 to 2003. Helicobacter 2005; 10:4-11. [PMID: 15691310 DOI: 10.1111/j.1523-5378.2005.00286.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Previous reports revealed no resistant strains of amoxicillin (AMPC), which is usually used in eradication therapy for H. pylori infection. However, the frequency and evolution of natural AMPC-resistant strains in the Japanese population remains unknown. AIM To assess the prevalence of H. pylori resistance against AMPC in the Tokyo area, a collection of 648 H. pylori strains isolated from patients with GI diseases from 1985 to 2003 was tested for their sensitivity to AMPC. METHODS The susceptibility of the strains was assessed by determination of the minimal inhibitory concentration (MIC) using the E-test and/or the Dry-plate method. The susceptibility breakpoints of AMPC for H. pylori were: sensitive (AMPC-S); MIC < 0.04 microg/ml, intermittent resistance (AMPC-I); 0.04-1, resistant (AMPC-R); > 1. RESULTS No AMPC-R strains were detected in the strains isolated between 1985 and 1996, while the rate of resistance was determined to be 1.1%, 2.1%, 5.4%, 5.6%, 0%, 8.8%, and 1.5% every year, respectively, from 1997 to 2003. The percentage of AMPC-I strains increased from 2000 to 2003. The total eradication rate of H. pylori in the patients who received triple therapy containing AMPC was 81.4% (214/263). Classified as above, the rates of AMPC-S, AMPC-I, and AMPC-R were 84.6%, 77.8%, 25%, respectively. CONCLUSION H. pylori resistance to AMPC is still rare in Japan, although the percentage of AMPC-I strains has increased over the last 4 years. The frequency of isolation of strains showing true resistance to AMPC may increase in the future, along with an increase in the frequency of isolation of AMPC-I strains.
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Affiliation(s)
- Kazuhiro Watanabe
- Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
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Nahar S, Mukhopadhyay AK, Khan R, Ahmad MM, Datta S, Chattopadhyay S, Dhar SC, Sarker SA, Engstrand L, Berg DE, Nair GB, Rahman M. Antimicrobial susceptibility of Helicobacter pylori strains isolated in Bangladesh. J Clin Microbiol 2004; 42:4856-8. [PMID: 15472362 PMCID: PMC522322 DOI: 10.1128/jcm.42.10.4856-4858.2004] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Antimicrobial susceptibility of 120 Helicobacter pylori isolates to metronidazole, tetracycline, clarithromycin, and amoxicillin was determined, and 77.5, 15, 10, and 6.6% of the isolates, respectively, were resistant. Only rdxA inactivation and both rdxA and frxA inactivation were responsible for metronidazole resistance in 66% (8 of 12) and 33% (4 of 12) of the isolates, respectively.
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Affiliation(s)
- Shamsun Nahar
- International Center for Diarrhoeal Disease Research, Dhaka, Bangladesh
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Abstract
The discovery that most stomach diseases are a consequence of an Helicobacter pylori infection has completely changed the management of stomach diseases. Antibacterials are the treatment of choice in addition to proton pump inhibitors (PPIs) or ranitidine bismuth. We are now faced with the problem of antimicrobial resistance, which is the main cause of treatment failure. H. pylori acquires resistance essentially via point mutations, and today this phenomenon is found with most antibacterials. The most important resistance to consider is that to clarithromycin, since it is the first-choice antibacterial and clarithromycin resistance is highly clinically significant. Quadruple therapy or triple therapies with amoxicillin-metronidazole or tetracycline-metronidazole and a PPI or ranitidine bismuth can then be used despite a possible resistance to metronidazole if the strain is resistant to clarithromycin. Resistance to both clarithromycin and metronidazole may lead to the use of other combinations, i.e. amoxicillin-rifabutin, amoxicillin-levofloxacin or amoxicillin-furazolidone. Resistance to any of these drugs means their use must be avoided. In some instances, it may also be advisable to prescribe amoxicillin as the sole antibacterial, or to use a quadruple therapy with furazolidone instead of metronidazole. Although it is theoretically possible to cure a drug-resistant H. pylori infection, a practical limitation is the availability of the drugs in certain countries. Furthermore, the progressive increase in drug resistance warrants the need for new antibacterials in the near future.
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Affiliation(s)
- Francis Mégraud
- Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, Bordeaux, France.
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Ruzsovics A, Molnar B, Tulassay Z. Review article: Deoxyribonucleic acid-based diagnostic techniques to detect Helicobacter pylori. Aliment Pharmacol Ther 2004; 19:1137-1146. [PMID: 15153166 DOI: 10.1111/j.1365-2036.2004.01934.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Helicobacter pylori is an important cause of many gastrointestinal disorders, ranging from chronic gastritis to gastric lymphoma and adenocarcinoma. The deoxyribonucleic acid-based assays have the potential to be a powerful diagnostic tool given its ability to specifically identify H. pylori deoxyribonucleic acid. Markers used to include general H. pylori structures and pathogenetic factors like ureaseA, cagA, vacA, iceA. Deoxyribonucleic acid or bacterial ribonucleic acid for polymerase chain reaction assays can be collected from gastric biopsy, gastric juice, stool, buccal specimens. Polymerase chain reaction can yield quantitative and genotyping results with sensitivity and specificity that approaches 100%. A clear trend in the direction of the determination of quantitative H. pylori infection by real-time polymerase chain reaction can be observed. Fluorescent in situ hybridization is suggested for routine antibiotic resistance determination. To identify the organism, deoxyribonucleic acid structure and its virulence factors may be feasible by using oligonucleotide microarray specifically recognizing and discriminating bacterial deoxyribonucleic acid and various virulence factors. Deoxyribonucleic acid-based H. pylori diagnosis yields higher sensitivity, however, specificity requires sophisticated labour environment and associated with higher costs.
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Affiliation(s)
- A Ruzsovics
- Semmelweis University, Faculty of Medicine, Second Department of Medicine Budapest, Budapest, Hungary
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Dore MP, Realdi G, Sepulveda AR, Graham DY. Detection of genomic Helicobacter pylori DNA in the blood of patients positive for the infection. Dig Liver Dis 2003; 35:839-40. [PMID: 14674676 DOI: 10.1016/s1590-8658(03)00450-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Perna F, Gatta L, Figura N, Ricci C, Tampieri A, Holton J, Miglioli M, Vaira D. Susceptibility of Helicobacter pylori to metronidazole. Am J Gastroenterol 2003; 98:2157-61. [PMID: 14572561 DOI: 10.1111/j.1572-0241.2003.07681.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The reliability of the Epsilometer-test (E-Test) and the disk diffusion (DD) method in the assessment of susceptibility of Helicobacter pylori (H. pylori) to metronidazole has recently been questioned, with possible clinical implications for the management of patients undergoing H. pylori eradication. The aims of this study were: 1) to compare the E-Test and disk diffusion methods to the agar dilution method for determining the susceptibility of H. pylori to metronidazole; and 2) to investigate whether potential discrepancies could be caused by the simultaneous presence of metronidazole susceptible and metronidazole resistant bacterial subpopulations. METHODS A total of 109 H. pylori strains from 121 consecutive patients were examined. All tests were carried out at the same time starting from primary plates. Agar dilution was performed according to National Committee for Clinical Laboratory Standard (NCCLS) standards, the E-Test according to the manufacturer's guidelines, and disk diffusion according to standard procedure using 5-mug metronidazole disks. Isolates were considered to be metronidazole resistant if the minimal inhibitory concentration was >8 mug/ml for the agar dilution and the E-Test, or if the inhibition zone around the disk was <20 mm for disk diffusion. Of 109 isolates, 43 were also investigated to detect mixed infection. Quantities of 100 mul of bacterial suspensions of each strain were seeded onto plain agar plates and plates containing 8 mug/ml of metronidazole. Cultures were considered to be mixed if the number of colonies on agar plates exceeded by at least 30% those on the metronidazole plates. RESULTS According to agar dilution, 57 strains (52.3%, 95% CI = 43-61.4) were metronidazole resistant. E-Test misdiagnosed two strains that were considered sensitive to metronidazole, but according to the agar dilution test they were resistant. Disk diffusion misdiagnosed three strains. Two of these strains (the same as the E-Test) were sensitive, but according to agar dilution they were metronidazole resistant; the third strain was resistant, but according to agar dilution it was sensitive. The percentages of discordance were 1.9 (95% CI = 0.5-6.6) and 2.8 (95% CI = 0.9-7.8), respectively, when the E-Test and disk diffusion were compared to agar dilution. Intertest variability among agar dilution and the E-Test showed that 39.4% (95% CI = 30.8-48.8) of minimal inhibitory concentrations were equivalent (within +/-1 log(2)), 60.6% (95% CI = 51.2-69.2) were major errors (more than +/-1 log(2)), and 3% (95% CI = 0.8-10.4) were very major errors (change in susceptibility pattern). Mixed infection was found in six of the 43 cases examined (13.9%). In four cases, metronidazole resistant strains were 1 log(10) less numerous than those that were metronidazole susceptible. In the remaining two cases, the metronidazole resistant strains were 2-3 log(10) less numerous, which caused the two misdiagnoses. CONCLUSIONS The E-Test and disk diffusion method are very good alternatives to agar dilution. Mixed infections are a possible cause of the discrepancies between these tests and the reference method.
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Affiliation(s)
- Federico Perna
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy
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Miehlke S, Kirsch C, Schneider-Brachert W, Haferland C, Neumeyer M, Bästlein E, Papke J, Jacobs E, Vieth M, Stolte M, Lehn N, Bayerdörffer E. A prospective, randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Helicobacter 2003; 8:310-9. [PMID: 12950604 DOI: 10.1046/j.1523-5378.2003.00158.x] [Citation(s) in RCA: 96] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Failure of primary anti-H. pylori therapy results in a high rate of antimicrobial resistance. Here, we investigated the efficacy of high-dose dual therapy and quadruple therapy as salvage treatments for eradication of H. pylori resistant to both metronidazole and clarithromycin. PATIENTS AND METHODS Patients with at least one treatment failure and infected with H. pylori resistant to both metronidazole and clarithromycin, were randomized to receive either omeprazole 4 x 40 mg and amoxicillin 4 x 750 mg; or omeprazole 2 x 20 mg, bismuthcitrate 4 x 107 mg, metronidazole 4 x 500 mg and tetracycline 4 x 500 mg. Both regimens were given for 14 days. In cases of persistent infection, a cross-over therapy was performed. RESULTS Eighty-four patients were randomized. Cure of H. pylori infection was achieved in 31 patients after dual therapy and in 35 patients after quadruple therapy (per protocol: 83.8% (95% CI, 67.9-93.8) and 92.1% (95% CI, 78.6-98.3), respectively (p=0.71); intention to treat: 75.6% (95% CI: 59.7-87.6) and 81.4% (95% CI: 66.6-91.6), respectively (p=0.60)). Cross-over therapy was performed in six of nine patients, four of whom were cured of the infection. CONCLUSION Both high-dose dual therapy and quadruple therapy are effective in curing H. pylori infection resistant to both metronidazole and clarithromycin in patients who experienced previous treatment failures.
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Affiliation(s)
- Stephan Miehlke
- Medical Department I, Technical University Hospital, Dresden, Germany
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Sun CQ, O'Connor CJ, Roberton AM. Antibacterial actions of fatty acids and monoglycerides against Helicobacter pylori. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 2003; 36:9-17. [PMID: 12727360 DOI: 10.1016/s0928-8244(03)00008-7] [Citation(s) in RCA: 133] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The bactericidal potencies of saturated and unsaturated fatty acids (FAs) and monoglycerides (MGs) against Helicobacter pylori were determined following short incubations with freshly harvested cells over a range of pHs. FAs and their derivatives with an equivalent-carbon number of 12 were the most potent: lauric acid had a minimum bactericidal concentration (MBC) at pH 7.4 of 1 mM, myristoleic and linolenic acid were the most potent unsaturated FAs (MBCs of 0.5 mM, pH 7.4), and monolaurin was the most potent MG (MBC 0.5 mM). Potencies of saturated FAs were increased sharply by lowering pH, and a decrease of only 0.5 pH units can cause a change from non-lethal to lethal conditions. Conversely, the bactericidal action of monolaurin was not pH-dependent. The bactericidal potencies of unsaturated FAs increased with degree of unsaturation. When more than one FA or FA plus MGs were present, their combined action was additive. Urea and endogenous urease did not protect H. pylori from the bactericidal action of FAs. These results suggest that H. pylori present in the stomach contents (but not necessarily within the mucus barrier) should be rapidly killed by the millimolar concentrations of FAs and MGs that are produced by pre-intestinal lipase(s) acting on suitable triglycerides such as milk fat.
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Affiliation(s)
- Cynthia Q Sun
- Department of Chemistry, The University of Auckland, Private Bag 92019, Auckland, New Zealand
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Mahady GB, Pendland SL, Stoia A, Chadwick LR. In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis. Phytother Res 2003; 17:217-21. [PMID: 12672149 DOI: 10.1002/ptr.1108] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Methanol extracts of the rhizomes of Sanguinaria canadensis, and the roots and rhizomes of Hydrastis canadensis, two plants used traditionally for the treatment of gastrointestinal ailments, were screened for in vitro antibacterial activity against 15 strains of Helicobacter pylori. The rhizome extracts, as well as a methanol extract of S. canadensis suspension-cell cultures inhibited the growth of H. pylori in vitro, with a MIC50 range of 12.5-50.0 microg/ml. Three isoquinoline alkaloids were identified in the active fraction. Sanguinarine and chelerythrine, two benzophenanthridine alkaloids, inhibited the growth of the bacterium, with an MIC50 of 50.0 and 100.0 microg/ml, respectively. Protopine, a protopine alkaloid, also inhibited the growth of the bacterium, with a MIC50 of 100 microg/ml. The crude methanol extract of H. canadensis rhizomes was very active, with an MIC50 of 12.5 microg/ml. Two isoquinoline alkaloids, berberine and beta-hydrastine, were identified as the active constituents, and having an MIC50 of 12.5 and 100.0 microg/ml, respectively.
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Affiliation(s)
- Gail B Mahady
- Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
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44
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Kim JJ, Tao H, Carloni E, Leung WK, Graham DY, Sepulveda AR. Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells. Gastroenterology 2002; 123:542-53. [PMID: 12145807 DOI: 10.1053/gast.2002.34751] [Citation(s) in RCA: 128] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Helicobacter pylori infection is a major gastric cancer risk factor. H. pylori gastritis occurs more frequently in individuals with microsatellite instability-positive than those with microsatellite instability-negative gastric cancers, raising the possibility that H. pylori infection affects DNA mismatch repair (MMR). The aim of this study was to determine the effect of H. pylori on the expression of DNA MMR proteins and RNA in gastric epithelial cells. METHODS Gastric cancer cell lines were cocultured with H. pylori, bacterial extracts, and Campylobacter jejuni or Escherichia coli. MutS (hMSH2 and hMSH6) and MutL (hMLH1, hPMS2, and hPMS1) DNA MMR protein and RNA levels were determined. RESULTS All cell lines examined showed decreased levels of MutS and MutL DNA MMR proteins in a dose-dependent manner after coculture with H. pylori strains. The reduction in DNA MMR protein levels was caused by heat-sensitive H. pylori products. The levels of DNA MMR proteins were affected by C. jejuni but not by E. coli. RNA levels of hMSH2 and hMSH6 were also reduced after exposure to H. pylori. CONCLUSIONS H. pylori infection of gastric epithelial cells leads to a decrease in DNA MMR proteins that is at least in part related to an H. pylori-induced decrease in messenger RNA levels of repair genes. These data suggest that H. pylori infection might lead to a deficiency of DNA MMR in gastric epithelial cells that may increase the risk of mutation accumulation in gastric mucosa cells and the risk of gastric cancer during chronic H. pylori infection.
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Affiliation(s)
- Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Gerrits MM, Schuijffel D, van Zwet AA, Kuipers EJ, Vandenbroucke-Grauls CMJE, Kusters JG. Alterations in penicillin-binding protein 1A confer resistance to beta-lactam antibiotics in Helicobacter pylori. Antimicrob Agents Chemother 2002; 46:2229-33. [PMID: 12069978 PMCID: PMC127293 DOI: 10.1128/aac.46.7.2229-2233.2002] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.3] [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 amoxicillin, an important component of combination therapies for H. pylori eradication. The isolation and initial characterization of the first reported stable amoxicillin-resistant clinical H. pylori isolate (the Hardenberg strain) have been published previously, but the underlying resistance mechanism was not described. Here we present evidence that the beta-lactam resistance of the Hardenberg strain results from a single amino acid substitution in HP0597, a penicillin-binding protein 1A (PBP1A) homolog of Escherichia coli. Replacement of the wild-type HP0597 (pbp1A) gene of the amoxicillin-sensitive (Amx(s)) H. pylori strain 1061 by the Hardenberg pbp1A gene resulted in a 100-fold increase in the MIC of amoxicillin. Sequence analysis of pbp1A of the Hardenberg strain, the Amx(s) H. pylori strain 1061, and four amoxicillin-resistant (Amx(r)) 1061 transformants revealed a few amino acid substitutions, of which only a single Ser(414)-->Arg substitution was involved in amoxicillin resistance. Although we cannot exclude that mutations in other genes are required for high-level amoxicillin resistance of the Hardenberg strain, this amino acid substitution in PBP1A resulted in an increased MIC of amoxicillin that was almost identical to that for the original Hardenberg strain.
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Affiliation(s)
- M M Gerrits
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
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McNulty C, Owen R, Tompkins D, Hawtin P, McColl K, Price A, Smith G, Teare L. Helicobacter pylori susceptibility testing by disc diffusion. J Antimicrob Chemother 2002; 49:601-9. [PMID: 11909833 DOI: 10.1093/jac/49.4.601] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The bacterium Helicobacter pylori is found in c. 40% of the population and is responsible for the development of duodenal disease. Triple treatment with a proton-pump inhibitor or bismuth salt plus two antibiotics is now commonplace in all patients diagnosed. As antibiotic resistance reduces treatment efficacy, it is time to consider routine susceptibility testing to guide individual patient treatment and surveillance of antibiotic resistance. There are no published nationally agreed standards for disc diffusion testing of H. pylori. After reviewing the literature, we recommend the following method for disc diffusion tests. A suspension of cultures < or = 4 days old equivalent to McFarland Standard no. 4 (10(8) cfu/mL) should be used on Mueller-Hinton or Columbia agar base with 5-10% blood, using a metronidazole disc strength of 5 Ig and a clarithromycin disc strength of 2 microg. Anaerobic pre-incubation of plates is unnecessary. A H. pylori control susceptible to metronidazole (e.g. NCTC 12822) should be used. Zone sizes with the Mueller-Hinton agar base for metronidazole testing are <16 mm resistant, 16-21 mm intermediate and >21 mm susceptible. We suggest that isolates in the intermediate zone should be re-tested by Etest. Zone sizes with the Columbia agar base for metronidazole testing are <10 mm resistant and > or = 10 mm susceptible. Co-infection with two strains, which may be a mixture of isolates susceptible and resistant to metronidazole leading to conflicting susceptibility results, occurs in 5-10% of patients. Zone sizes with Mueller-Hinton agar and Columbia blood agar for clarithromycin testing are resistant no zone and susceptible any zone.
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Affiliation(s)
- Cliodna McNulty
- Public Health Laboratory, Gloucestershire Royal Hospital, Great Western Road, Gloucester GL1 3NN, UK.
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Cuchí Burgos E, Forné Bardera M, Quintana Riera S, Lite Lite J, Garau Alemany J. [Evolution of the sensitivity of 235 strains of Helicobacter pylori from 1995 to 1998 and impact of antibiotic treatment]. Enferm Infecc Microbiol Clin 2002; 20:157-60. [PMID: 11996701 DOI: 10.1016/s0213-005x(02)72778-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND The aim of this study was to investigate the sensitivity of Helicobacter pylori to the antibiotics used in its eradication over a period of four years and to determine the influence of previous treatment on sensitivity. MATERIAL AND METHODS During the period from 1995 to 1998 we determined the sensitivity of 235 consecutive Helicobacter pylori isolates to amoxicillin, metronidazole, clarythromycin and tetracycline by means of E-test methodology. The MIC values found were related with the prior use of eradicating treatment. RESULTS The percentage of resistant strains were as follows: 23.5% to metronidazole, 12.9% to clarythromycin and 0.7% to tetracycline; none of the strains was resistant to amoxicillin. There were no significant changes in percentage of resistance to the drugs studied over the 4-year period. Resistance to metronidazole and clarythromycin was significantly higher (p 5 0.03 and p < 0.001 respectively) in strains isolated from patients who had received previous treatment. CONCLUSIONS Monitorization of H. pylori sensitivity to the drugs used in its eradication is particularly important in patients who have undergone prior treatment.
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Affiliation(s)
- Eva Cuchí Burgos
- Servicio de Microbiología, Hospital Mútua de Terrassa, Barcelona, Spain
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Kalach N, Benhamou PH, Bergeret M, Gottrand F, Husson MO, Barbier C, Dupont C, Raymond J. [Acquisition of secondary resistance after failure of a first treatment of Helicobacter pylori infection in children]. Arch Pediatr 2002; 9:130-5. [PMID: 11915493 DOI: 10.1016/s0929-693x(01)00720-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
AIMS To assess the frequency of acquisition of secondary Helicobacter pylori resistant-strains after a first course of antimicrobial treatment. PATIENTS AND METHODS A retrospective study was performed during the 1994-2000 period, in 15 girls and eight boys, mean age 10.9 +/- 4.8 years (1.4-17 years), with Helicobacter pylori gastritis (culture and antimicrobial susceptibility) presenting a failure of first course treatment, with during one week a proton pump inhibitor and amoxicillin together with either clarithromycin (n = 14) or metronidazole (n = 9). Two endoscopies were performed, the first at the time of diagnosis and the second after the failure of bacterial eradication demonstrated by a positive 13C urea breath test six weeks after the end of treatment. Antimicrobial susceptibility of all Helicobacter pylori strains was tested after each endoscopy and before starting a second course of the treatment. RESULTS Comparison of antimicrobial susceptibility before and after the first course of treatment showed that Helicobacter pylori strains were all sensitive to amoxicillin, clarithromycin-resistant in eight children (34.7%) before treatment vs 12 (52.1%) after treatment, p = 0.42, ns, metronidazole-resistant in 13 (56.5%) vs 12 (52.1%), p = 0.80, ns, and both clarithromycin and metronidazole-resistant in four (17.3%) vs seven (30.4%), p = 0.63, ns. Among the 14 children treated by a triple therapy including clarithromycin, three (21.4%) developed a secondary resistance to clarithromycin and in one metronidazole resistance was no more detected. Among the nine children treated with a triple therapy including metronidazole, none developed a secondary resistance to metronidazole and one developed a secondary resistance to clarithromycin. CONCLUSION This study shows the absence of amoxicillin-resistant strains, a high initial clarithromycin-resistant strains level (primary resistance), increasing after a first course of treatment, and for metronidazole a high initial level of resistance not influenced by treatment. Secondary clarithromycin-resistance of Helicobacter pylori strains following the first course of treatment could account for failure of bacterial eradication and suggests the importance of antimicrobial susceptibility.
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Affiliation(s)
- N Kalach
- Service de pédiatrie, hôpital Saint-Vincent-de-Paul, 82, avenue Denfert-Rochereau, 75674 Paris, France
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Poon SK, Chang CS, Su J, Lai CH, Yang CC, Chen GH, Wang WC. Primary resistance to antibiotics and its clinical impact on the efficacy of Helicobacter pylori lansoprazole-based triple therapies. Aliment Pharmacol Ther 2002; 16:291-6. [PMID: 11860412 DOI: 10.1046/j.1365-2036.2002.01184.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM To evaluate Helicobacter pylori primary resistance and its clinical impact on the efficacy of two lansoprazole-based eradication triple therapies. METHODS H. pylori-positive patients (n=228) were randomized to receive one of the 1-week regimens: lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g (LAC), or lansoprazole 30 mg, clarithromycin 500 mg and metronidazole 500 mg (LMC), each given twice daily. H. pylori status was assessed by 13C-urea breath test and culture at diagnosis and by 13C-urea breath test 6 weeks after therapy. Antibiotic susceptibility was determined by E-test (n=98). RESULTS The eradication rates with per protocol/ intention-to-treat analyses were: LAC (n=95/114) 83%/69% and LMC (n=96/114) 85%/72%. Primary resistance was 11% for clarithromycin, 41% for metronidazole and 0% for amoxicillin. Eradication in metronidazole-susceptible/-resistant strains was 85%/82% in LAC and 83%/63% in LMC. Significantly lower cure rates were observed in clarithromycin-resistant patients treated with LAC (95% vs. 0%, P < 0.001) and LMC (86% vs. 0%, P < 0.001). CONCLUSIONS One-week LAC and LMC are similarly effective therapies. Clarithromycin resistance significantly affected H. pylori eradication in both regimens.
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Affiliation(s)
- S K Poon
- Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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