ANTYBIOTYKOTERAPIA PRAKTYCZNA DZIERANOWSKA PDF

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An increasing resistance of Helicobacter pylori strains to antimicrobial agents is the serious therapeutic problem. The aim of this study was to compare the primary and secondary resistance of H. Material and Methods. MIC values of clarithromycin and levofloxacin were determined by the E -test method.

The present study has shown the increasing amount of resistant H. Helicobacter pylori H. The incidence of the infection is associated mostly with childhood as well as socioeconomic and sanitary conditions. Helicobacter pylori infection plays a major role in peptic ulcer disease, low-grade mucosa-associated lymphoid tissue MALT lymphoma, and gastric cancer.

Thanks to the discovery of this pathogen by Marshall and Warren in , peptic ulcer diseases are no longer chronic but can be cured by the regimen of antibiotics and gastric antisecretory drugs [ 3 ]. The preferred eradication therapy is triple or quadruple therapy, which is combined therapy including three types of drugs: antisecretory drugs, cytoprotectants, and antibiotics and chemotherapeutic drugs.

Current guidelines from the American College of Gastroenterology and the European Helicobacter Study Group EHSG recommend a clarithromycin-based triple therapy for the first 5 days a proton pump inhibitor PPI plus amoxicillin and clarithromycin or a bismuth quadruple therapy a PPI plus bismuth, metronidazole and tetracycline [ 4 , 5 ]. Obligatory procedures for the management of H. The First-Line Treatment. The Second-Line Treatment. The Third-Line Treatment. Evaluation of the susceptibility of the strains to the currently used antimicrobial agents: amoxicillin, metronidazole, clarithromycin, and tetracycline; possible introduction of levofloxacin; adding a probiotic [ 6 ].

Recommendations of PTG were published in and were the first polish recommendations which allow introduction of levofloxacin in treatment of H.

The increasing level of antibiotic resistance in H. In addition, it recommends local permanent monitoring of H. Emerging evidence indicates that resistance rates to metronidazole could constitute the real problem.

On the other hand, some scientists believe that the resistance might be overcome with increased doses of metronidazole [ 10 ]. The rate of clarithromycin resistance is increasing, and one of the reasons of this increase is likely to be a greater use of clarithromycin in the treatment of respiratory tract infections in the community.

Clarithromycin resistance in H. In Poland the resistance of H. Therefore, in accordance with the Maastricht recommendations, in Poland clarithromycin and metronidazole should not be used without previous susceptibility testing [ 5 ].

When the first-line therapy is unsuccessful, we need the effective second-line therapy. Evolving research has demonstrated that the introduction of new drugs, such as levofloxacin and rifabutin, provides new possibilities of treatment [ 7 , 10 , 11 ].

However, the current recommendation of PTG is to entertain the introduction of levofloxacin as the third-line empirical treatment [ 6 ]. Nevertheless, some studies carried out by Molina-Infante in Spain examined the introduction of levofloxacin in the first-line treatment in triple and sequential regimens and demonstrated the advantage of levofloxacin in both combinations.

Levofloxacin may be a good alternative to clarithromycin in the region with high percentage of resistant H. As a result of frequent resistance of H. Levofloxacin, a bactericidal fluoroquinolone of the 3rd generation antibiotics, has also the activity in the second-line therapy. Levofloxacin may be used as a substitute for clarithromycin in either a standard triple or sequential regimen. A large study comparing antibiotics in either of regimens shows a clear advantage to levofloxacin in both combinations.

It has been proposed that levofloxacin-based regimens are the most beneficial in areas where clarithromycin resistance is higher [ 13 — 16 ]. A rapidly increasing rate of fluoroquinolone resistance was reported in several countries [ 7 ]. The apparently rapid rate at which fluoroquinolone resistance seems to develop may limit the use of levofloxacin in H.

Since the resistance to antimicrobials is a major cause of eradication failure, the monitoring of antimicrobial resistance of H. For developing countries this monitoring should probably also include other antimicrobials used in the eradication therapy [ 18 — 20 ]. Therefore, the aim of this prospective study was to assess the primary and secondary resistance of H. The plan of the study was approved by the Bioethical Commission of the Jagiellonian University, and each patient signed the informed consent for the participation in the study.

During gastroscopy two biopsy specimens bioptates were taken from each patient. Bioptates were collected from the antrum and the body of the stomach. Bioptate was homogenized in glass sterile mortars to ensure a homogeneous distribution of bacteria in the whole specimen. The presence of H. Furthermore, Gram-staining preparation from the colony was performed to confirm the presence of Gram-negative spiral bacteria. The susceptibility of H. The susceptibility to clarithromycin and levofloxacin was tested for each H.

From the pure H. Then, E -test stripes with the clarithromycin and levofloxacin gradient were placed on plates according to manual of the manufacturer AB Biodisk, E -test technical manual , separately for clarithromycin and levofloxacin. The determination of MIC values was carried out against the reference H. The accepted significance level was 0. In cases where the expected values were less than 5, the Yates correction was used.

The association between the primary and the secondary H. Moreover, the statistical analysis tested the differences between the level of primary and secondary H. Among patients with dyspeptic symptoms admitted to the study between January and December , the presence of H. The prevalence of H. The group of H. The average age of this group of patients was In total, 43 strains were derived from patients who had never been treated for H.

The percentage of primary and secondary H. Susceptibility to clarithromycin and levofloxacin was tested for all H. The obtained MIC values ranged from 0. Mean MIC values were as follows: 1. In total, in the years —, the ratio of H. The ratio of H. Comparison of resistance of H. In the years —, strains were isolated.

The comparison of the H. Nevertheless, the amount of H. Activity of clarithromycin and levofloxacin against primary and secondary H. Variations of the prevalence of resistant H. The resistance of H. For example, in France it increased from 3. In another country, such as Iran, the resistance of H. Our study has shown that in Poland there is also a significant increase of H. Many studies have shown that resistance to fluoroquinolones is easily acquired and is due to point mutations in gyrA genes [ 21 , 23 , 25 , 26 ].

The higher rate of H. Studies conducted in Belgium over the last 20 years — show the correlation between consumption of antibiotics and the rates of resistant H. Also another study, carried out by Cabrita et al. Nevertheless, there is no commonly available information about usage of antibiotics and chemotherapeutics in outpatient clinic in Poland, but, as known, fluoroqinolones are used not only in H.

This usage of fluoroquinolones and cited studies allows to conclude that increasing resistance of H. Susceptibility testing has not been routinely performed and anti- H. However, due to the fact that the resistance to levofloxacin is quickly acquired, susceptibility testing should be routinely carried out to enable properly selecting treatment model, or levofloxacin should not be used commonly but only in the rescue third-line therapy, when treatment with clarithromycin and metronidazole failed as it is recommended by EHSG and PTG [ 5 , 6 ] to avoid the further increase of resistance of H.

Moreover, Marzio et al. It has been suggested that triple therapy with levofloxacin, amoxicillin, and PPI should not be used without previous susceptibility test in the region where primary resistance of H. According to EHSG and the Polish Society of Gastroenterology recommendations, there are three schemes of treatment which suggested the use of levofloxacin as the third-line treatment [ 5 , 6 ]. Moreover, several studies which showed the efficacy of the third-line rescue therapy with levofloxacin were carried out [ 31 , 33 , 34 ].

Furthermore, levofloxacin was also successfully tested as a good substitute of clarithromycin in the area with the high prevalence of clarithromycin-resistant H. Positive results of these studies were likely to contribute to the increased use of levofloxacin instead of clarithromycin in the empirical treatment. Apart from that, fluoroquinolones as drugs with a broad spectrum of activity against bacteria are commonly used in the treatment of many diseases, not only in the treatment of H.

An interesting result shown by our research is the change in the profile of the susceptibility of H. The resistance to clarithromycin decreased in comparison to the previous years — The current level of resistance of H.

This change may be caused by the lower consumption of this antimicrobial agent and higher consumption of levofloxacin instead of clarithromycin. This proposal is due to the changes in the profile of H. It is a hypothesis which would require further detailed research and analysis. If the level of resistance to levofloxacin continues to rise and the downward trend of resistance to clarithromycin is sustained, a similar situation may occur in Poland.

All things considered, it should be noted that the resistance of H.

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An increasing resistance of Helicobacter pylori strains to antimicrobial agents is the serious therapeutic problem. The aim of this study was to compare the primary and secondary resistance of H. Material and Methods. MIC values of clarithromycin and levofloxacin were determined by the E -test method. The present study has shown the increasing amount of resistant H. Helicobacter pylori H.

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