Antimicrobial resistance in Helicobacter pylori: a global overview.

Helicobacter pylori resistance to antimicrobial agents is of particular concern because it is a major determinant in the failure of eradication regimens. Antimicrobial drug resistance has been reported to occur for nitroimidazoles, macrolides, fluoroquinolones, rifampin and tetracyclines. Resistance to nitroimidazoles is the most common, in the range of 30-40% on the average in Europe while the overall prevalence rate of resistance to macrolides is lower, probably ranging between 2-10% in most countries. Development of secondary (acquired) resistance to nitroimidazoles and to the macrolides usually occurs as a rule (> 70-100%) in case of failed eradication therapy. Data available from several centres seems however to indicate that a significant shift towards increasing resistance to metronidazole and to the macrolides might have possibly occurred in many countries over the last years. Resistances to both metronidazole and to clarithromycin are the most significant ones because they influence the success of the treatments although this seems to be less marked and more dependent on the treatment regimens considered in the case of metronidazole resistance than in the setting of clarithromycin resistance. These differences may in part relate to methodological variations and to the inherent difficulties in assessing the susceptibility of H. pylori to metronidazole. It is possible that different resistance cut-off might also have to be considered for metronidazole depending on the treatment regimens administered. The mechanisms of resistance have been well defined for the macrolides and are beginning to be unraveled for the nitroimidazoles. In all cases, resistance of H. pylori to antimicrobial agent seems to be due to the development of single mutational events in chromosomal genes rather than to the acquisition of exogenous resistance genes. Owing to the restricted ability of microbiology laboratories with expertise in H. pylori culture and the lack of standardised methodology for susceptibility testing, H. pylori culture is not often performed routinely. It should however be considered after documented treatment failure or in patients from a geographic area or of an ethnic origin with higher likelihood of antimicrobial drug resistance. Likewise it is deemed very important to institute national and regional surveillance programs to follow the evolution of H. pylori resistance and to better adapt treatment regimens to changes in resistance patterns.