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Resistance of Helicobacter pylori to macrolides and nitroimidazole compounds. The current situation
F Mégraud1, A Occhialini, H P Doermann
1Laboratoire de Bactériologie-Enfants, Hopital Pellegrin-Bordeaux, France.
Abstract:
Macrolides and nitroimidazoles are among the antibiotics currently used for Helicobacter pylori eradication for which an acquired resistance may occur. Macrolides bind tightly to H. pylori ribosomes and inhibit protein synthesis. Resistance has been found associated with a lack of binding and to a point mutation in position 2058 or 2059 of the 23S ribosomal RNA genes (domain V). This resistance is easy to detect and is clinically relevant. There is a decrease of up to 40% in the success rate of triple therapies including clarithromycin when there is a resistance of H. pylori to this compound. Nitroimidazoles must be reduced to be active on the bacterial DNA. Resistance is associated with a lack of reduction of the NO2 group. But this reduction can be influenced by the redox potential of the environment. The genetic background is not yet known. There are discrepancies between the different methods used to test susceptibility to nitroimidazole; the best method which is now in the process of being standardized, is the agar dilution method. The clinical relevance of this resistance has been questioned. However, despite all the problems highlighted, there is still a difference between strains categorized as susceptible or resistant with regard to the eradication rate of H. pylori. This difference is greater when nitroimidazole is associated with amoxicillin rather than with clarithromycin.
Insights
Antibiotic resistance in Helicobacter pylori is a growing concern. Resistance to macrolides and nitroimidazoles impacts eradication success rates, necessitating further research into resistance mechanisms and standardized testing.
Area of Science:
- Microbiology
- Pharmacology
- Genetics
Background:
- Macrolides and nitroimidazoles are key antibiotics for Helicobacter pylori eradication.
- Acquired antibiotic resistance can compromise treatment efficacy.
- Understanding resistance mechanisms is crucial for effective H. pylori infection management.
Purpose of the Study:
- To review and summarize the mechanisms of acquired resistance to macrolides and nitroimidazoles in Helicobacter pylori.
- To discuss the clinical relevance and detection methods for H. pylori resistance to these antibiotic classes.
Main Methods:
- Review of existing literature on macrolide and nitroimidazole resistance in H. pylori.
- Analysis of resistance mechanisms, including ribosomal RNA mutations for macrolides and redox potential influence for nitroimidazoles.
- Evaluation of diagnostic methods for susceptibility testing.
Main Results:
- Macrolide resistance is linked to 23S ribosomal RNA gene mutations (positions 2058/2059), impacting protein synthesis and reducing clarithromycin-based therapy success by up to 40%.
- Nitroimidazole resistance involves impaired reduction of the NO2 group, influenced by environmental redox potential; genetic basis is unclear.
- Discrepancies exist in nitroimidazole susceptibility testing, with agar dilution emerging as the standardized method; clinical relevance is debated but impacts eradication rates.
Conclusions:
- H. pylori resistance to macrolides and nitroimidazoles poses a significant challenge to eradication therapy.
- Standardized susceptibility testing, particularly the agar dilution method for nitroimidazoles, is essential for clinical decision-making.
- Further research into nitroimidazole resistance mechanisms and optimization of combination therapies is warranted.