How antibiotic resistances could changeHelicobacter pyloritreatment: A matter of geography?

Abstract

Therapeutic management of Helicobacter pylori (H. pylori) remains an unsolved issue. Indeed, no therapeutic regimen is able to cure the infection in all treated patients, and in many the infection persists despite the administration of several consecutive standard therapies. Although antibiotic resistance reports describe alarming results, the outcome of therapeutic regimens does not seem to parallel this scenario in most cases, since a successful performance is often reached in more than 80% of cases. However, the phenomenon of increasing antibiotic resistance is being closely studied, and the results show controversial aspects even in the same geographic area. For the continents of Europe, America, Asia, Africa, and Oceania, minimal and maximal values of resistance to the main antibiotics (clarithromycin, amoxicillin, metronidazole, and levofloxacin) feature wide ranges in different countries. The real enigma is therefore linked to the several different therapeutic regimens, which show results that often do not parallel the in vitro findings even in the same areas. A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts. Moreover, not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome. The additional use of probiotics may help to reduce adverse events, but their therapeutic impact is doubtful. In conclusion, the "ideal therapy", paradoxically, appears to be a "utopia", despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H. pylori. The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide. On these bases, one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances. In this context, geography must be considered a relevant matter.

Antibiotic treatment forHelicobacter pylori: Is the end coming?

“…Resistance to these antibiotics is thought to be the main cause of eradication failure [27][28][29] . Antibiotic resistance is discovered by bacterial culture-based techniques (E-test, modified disk diffusion, agar dilution method, and breakpoint susceptibility test) and molecular methods [polymerase chain reaction (PCR), real-time PCR, allele-specific PCR, sequencing, and fluorescent in situ hybridization] [30] . Although these methods are useful for examining antibiotic resistance, their implementation at the early stages of H. pylori remains impractical due to the time required to obtain results and the high cost of the tests.…”

“…Clarithromycin is a macrolide antibiotic that inhibits protein synthesis by binding to and slowing the actions of the bacterial ribosome [30] . Clarithromycin resistance is due to three point mutations at A2142C, A2142G, and A2143G in the 23s rRNA gene [31] .…”

“…The mechanism mediating resistance to metronidazole is complex. Modifications in the rdxA gene, assumed to be point mutations, are considered a primary cause [30] . Metronidazole resistance may also influence the treatment outcome, although it is generally considered less clinically important than clarithromycin resistance [52,53] .…”

“…Another study showed that 80% of strains in Mexico were resistant to metronidazole [55] . Overall, metronidazole resistance is > 50% in much of the world but there are reports that metronidazole resistance has declined in Northern Europe [9,30] , while in the United States and Europe, the metronidazole resistance rate was reported to be < 40% [30,56] , and 22.5% in 102 isolates from Norway [57] . However, in Central and Southern Europe, resistance rates remain markedly higher-34.9% in France and 32.7% in Germany [47,58] .…”

“…Amoxicillin is a beta-lactam antibiotic that was first used for H. pylori therapy [25] . Unlike clarithromycin and metronidazole, amoxicillin resistance rates are low worldwide [30] : 0% or < 1% in Europe [30] . However, other studies revealed high amoxicillin resistance rates in Iran, Japan, and Cameroon [37,45,54] .…”