Drug resistance in Helicobacter pylori

Journal of Research in Medical Sciences the Official Journal of Isfahan University of Medical Sciences, 2013

Helicobacter, 2002

PICOLI(1), Luiz Edmundo MAZZOLENI(2), Heriberto FERNÁNDEZ(3), Laura Renata DE BONA(4), Erli NEUHAUSS(5), Larisse LONGO(4) & João Carlos PROLLA(6) SUMMARY Introduction: Helicobacter pylori is a bacteria which infects half the world population and is an important cause of gastric cancer. The eradication therapy is not always effective because resistance to antimicrobials may occur. The aim of this study was to determine the susceptibility profile of H. pylori to amoxicillin, clarithromycin and ciprofloxacin in the population of Southern Brazil. Material and methods: Fifty four samples of H. pylori were evaluated. The antibiotics susceptibility was determined according to the guidelines of the British Society for Antimicrobial Chemotherapy and the Comité de l'Antibiogramme de la Société Française de Microbiologie. Results: Six (11.1%) H. pylori isolates were resistant to clarithromycin, one (1.9%) to amoxicillin and three (5.5%) to ciprofloxacin. These indices of resistance are considered satisfactory and show that all of these antibiotics can be used in the empirical therapy. Conclusion: The antibiotics amoxicillin and clarithromycin are still a good option for first line anti-H. pylori treatment in the population of Southern Brazil.

Dig Liver Dis, 2000

Eradication of Helicobacter pylori (H. pylori) is attempted in many disease conditions and could be the means of preventing gastric cancer, but it is difficult to achieve. At present, there are no single agents capable of curing the infection, and combination regimens are needed to eradicate H. pylori. Many agents, including antibiotics and antisecretory agents, have been used and those that have resulted from different combinations of agents are numberless. However, they can be grouped into a few major categories. The so-called standard, or bismuth based, triple therapy comprises bismuth, metronidazole and tetracycline. This regimen can achieve high eradication rates and because of its low cost, has also been considered, for years, as the gold standard; however, because of its complexity and sometimes severe side-effects, its effectiveness is limited and significantly lower eradication rates appear when properly calculated by the intention-to-treat analysis. Dual therapy is another landmark in H. pylori eradication. Dual therapies comprise a proton pump inhibitor (PPI) plus one antibiotic; initially, it was amoxycillin, later clarithromycin was used. Preliminary studies claimed that omeprazole plus amoxycillin, administered for two weeks, could eradicate H. pylori in more than 90% of the cases. However, subsequent studies produced inconsistent results and accepted eradication rates by dual therapies are less than 60%. Both standard triple and dual therapies, however, in spite of their low applicability, should be considered as milestones because they have provided the background rationale for the development of short-term low-dose PPI triple therapies. A simple, safe, short-term low-dose triple therapy including a PPI and two antibiotics, has been developed in response to the problems encountered with standard triple and dual therapies. In fact, an analysis of the many studies in the literature has shown that, in addition to the hostile gastric environment that reduces bioavailability of antibiotics in the stomach, two other factors, namely side effects and patient non-compliance were significantly associated with treatment failure. These observations led to the hypothesis that by increasing the intragastric pH with a PPI and by using two antibiotics of high efficacy and low MIC, at low dosages and with a small number of tablets, drug availability would be increased, side-effects reduced and compliance improved. Initial eradication rates reported by this regimen and approaching 100% were regarded with skepticism; however, soon afterwards, many other authors from different countries were able to confirm the excellent performance of regimens based on the principle of administering a PPI plus two antibiotics, clarithromycin, metronidazole or amoxycillin, for one week. Furthermore, some time later, the rationale of adding a PPI and reducing the administration period to one week was also applied to the standard bismuth triple therapy resulting in the so-called quadruple therapy, nowadays the other well-established regimen for H. pylori eradication. The continuous flow of data in the literature confirms that the above-mentioned regimens should still be considered for the treatment of H. pylori. Nevertheless, there are many factors affecting H. pylori eradication, including not only side-effects and patient compliance, but also disease condition [peptic ulcer disease (PUD), non ulcer dyspepsia (NUD), etc.], different ge-5207

Alimentary Pharmacology & Therapeutics, 2000

Journal of Gastrointestinal and Liver Diseases Jgld, 2010

Prevalence of H. pylori antibiotic resistance is increasing worldwide, and it is the main factor affecting efficacy of current therapeutic regimens. Our aim was to review recent data on H. pylori resistance towards antibiotics in different countries. Methods. A systematic review of studies concerning primary H. pylori antibiotic resistance published through January 2006 to December 2009 was performed. Data were analyzed according to geographic area, age, sex, and gastroduodenal pathology. Results. The overall H. pylori antibiotic resistance rates were 17.2% (95% CI: 16.5-17.9%) for clarithromycin, 26.7% (95% CI: 25.2-28.1%) for metronidazole, 11.2% (95% CI: 9.6-12.7%) for amoxycillin, 16.2% (95% CI: 14.4-18%) for levofloxacin, 5.9% (95% CI: 4.7-7.1%) for tetracycline, 1.4% (95% CI: 0.81-9%) for rifabutin and 9.6% (95% CI: 8.5-10.7%) for multiple antibiotics. Prevalence rate of clarithromycin, metronidazole, and levofloxacin resistance significantly increased from Europe to Asia, America and Africa. Tetracycline resistance is low (<3%) in all countries, but Africa (43.9%). Prevalence of clarithromycin resistance was higher in non-ulcer dyspepsia patients, whilst metronidazole resistance was higher in peptic ulcer patients. Both resistances were significantly higher in female than in male patients. Data regarding amoxicillin resistance are highly conflicting. Conclusion. The worldwide H. pylori antibiotic resistance towards different antibiotics has increased. Such a phenomenon may affect therapeutic management in different countries.

on behalf of the Study Group participants* ABSTRACT Objective Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori infection. A study was conducted to assess prospectively the antibacterial resistance rates of H pylori in Europe and to study the link between outpatient antibiotic use and resistance levels in different countries. Design Primary antibiotic resistance rates of H pylori were determined from April 2008 to June 2009 in 18 European countries. Data on yearly and cumulative use over several years of systemic antibacterial agents in ambulatory care for the period 2001e8 were expressed in Defined Daily Doses (DDD) per 1000 inhabitants per day. The fit of models and the degree of ecological association between antibiotic use and resistance data were assessed using generalised linear mixed models. Results Of 2204 patients included, H pylori resistance rates for adults were 17.5% for clarithromycin, 14.1% for levofloxacin and 34.9% for metronidazole, and were significantly higher for clarithromycin and levofloxacin in Western/Central and Southern Europe (>20%) than in Northern European countries (<10%). Model fit improved for each additional year of antibiotic use accumulated, but the best fit was obtained for 2005. A significant association was found between outpatient quinolone use and the proportion of levofloxacin resistance (p¼0.0013) and between the use of longacting macrolides only and clarithromycin resistance (p¼0.036). Conclusion In many countries the high rate of clarithromycin resistance no longer allows its empirical use in standard anti-H pylori regimens. The knowledge of outpatient antibiotic consumption may provide a simple tool to predict the susceptibility of H pylori to quinolones and to macrolides and to adapt the treatment strategies.

World Journal of Gastroenterology, 2017

The management of Helicobacter pylori (H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture-or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori , but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available cultureor molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.

2004

Background: Clarithromycin resistance is an increasing problem in this part of the world and it potentially has an impact on the eradication rate of first line triple therapy (proton pump inhibitor- AmoxicillinClarithromycin) for Helicobacter pylori (H. pylori) infection. Objective: This study was designed to determine the effect of clarithromycin resistance on the efficacy of Pantoprazole-Amoxicillin-Clarithromycin for H. pylori eradication in Thai patients with non-ulcer dyspepsia (NUD). Patients and Methods: A total of 69 patients with NUD who had undergone upper endoscopy for dyspeptic symptom and had H. pylori infection as determined by positive urease test and positive culture for H. pylori were enrolled in this study. Minimal inhibitory concentrations (MICs) of Clarithromycin were identified using Epsilometer test (E-test). The value of MICs cutpoint for Clarithromycin resistant was &gt;1 microgram/ml. There were 16 patients who had Clarithromycin resistant H. pylori and 53 p...

International Journal of Antimicrobial Agents, 1999

Helicobacter pylori is very susceptible in vitro to most antibiotics, but when they are used in the clinical setting, eradication of the bacteria from the gastric mucosa is not obtained. Dual or triple therapy including two of the following antibiotics: amoxicillin, tetracycline, metronidazole or clarithromycin, plus a proton pump inhibitor, bismuth salt or ranitidine bismuth citrate is the most frequently used. Various in vitro susceptibility methods have been used: disk diffusion, agar dilution and Epsilometer test (E-test). Metronidazole resistance among H. pylori strains is now found worldwide, and resistance rates vary according to the population studied. It is higher in developing than in developed countries and it could reach 80-90% in Africa. The prevalence on clarithromycin resistance is much lower, usually below 10%, although very high values are reported in Peru. Infection with metronidazole-or clarithromycin-resistant H. pylori strains is correlated with treatment failure when using regimens including these antibiotics.