Management of Helicobacter pylori infections

With >50 % of the world’s population colonized by Helicobacter pylori it is one of the most prevalent human pathogens [1]. Infection with H. pylori is associated with chronic gastritis, duodenal ulcer, gastric cancer and even gastric adenocarcinoma [2]. Infection is usually acquired in childhood via person-to-person fecal-oral, oral-oral, or gastro-oral transmission being the most likely route of infection [3]. When ingested the bacterium colonizes the mucous layer covering the epithelial cells of the stomach and this induces an immune response that in spite of its vigor is unable to eliminate the bacterium [4]. The chronic infection that results from this vigorous but typically inadequate immune response induces gastric damage that is associated with digestive disorders ranging from chronic gastritis to peptic ulcer disease, and gastric cancer, but in most cases H. pylori infected patients remain asymptomatic for a long time [5]. In contrast to many other infectious agents the final outcome of a H. pylori infection is different for each infection and is dependent on both host and bacterial factors [1]. The large genetic variation observed among clinical strains of H. pylori is thought to be an important determinant in the specific local establishment of this colonization and determines in large part the development of the potential disorders that result from the infection [6]. The remarkable genetic and phenotypic diversity observed in H. pylori is thought to be driven by the need to adapt to the harsh and patient specific conditions of the gastric environment that often result in the genesis of various subpopulations (quasispecies) within single patients [7]. This results in each infected person potentially carrying genetically unique microorganisms existing only in that particular patient [7, 8]. Depending on the presence of specific H. pylori virulence factors such as dupA, cagA, vacA and homB the bacterium usually colonizes the antral mucosa of human stomach [8]. Once this primary colonization is established it induces an inflammation that remains largely asymptomatic (Fig. 1) [9, 10]. In fact, an acute infection and subsequent gastritis precede the more severe digestive disorders such as gastric bleeding, peptic ulcers, and gastric cancer known to be associated with H. pylori infection (Fig. 1) [10]. While a long list of antibiotics has been tested for their effectiveness on H. pylori only a handful of them can be used for effective H. pylori eradication. Treatment options are further reduced as effective therapeutic regimen requires a combination of two or three antibiotics and a gastric acid suppressive drug [11]. Finally, in H. pylori antibiotic resistance to these drugs rapidly emerges as the resistance against all these drugs does not require the introduction of specific genes, but in all cases is based on a single point mutation in an existing housekeeping gene thus and obviously this further reduces a broad clinical efficacy significantly [4, 12, 13]. In parallel with emergence of multidrug resistant bacteria in other bacterial species, we need to accept that there is a rapid and ongoing reduction of the effective lifespan of antibiotics for clinical applications [14]. This has resulted in a situation where the big companies stopped or reduced their efforts to develop new antibiotics. While vaccination may be a practical approach for many pathogens, in the case of H. pylori vaccines do not seem to represent a viable option as sterilizing immunity is not considered an endpoint for now [15, 16]. As currently vaccines and pre/probiotics do not offer realistic H. pylori eradication strategies antibiotic treatment is currently the only available option to effectively reduce the gastrointestinal disorders resulting from H. pylori infection [17‐19]. For now the further increase of antimicrobial resistance in H. pylori is being endangered by clinicians that frequently prescribe clarithromycin for patients suffering from upper respiratory diseases. Especially in developing countries many of these respiratory disease patients will also be colonized with H. pylori, but as here H. pylori infection is still in its early stage it will probably not have resulted in any significant disease symptoms and thus go unnoticed. Treating these patients with antibiotics with what should be considered for H. pylori as low dose, relative short period, and in the absence of an acid suppressive agent will not eradicate the H. pylori colonization but instead is very likely to promote the generation of resistant H. pylori. Hence we would need to create the awareness amongst clinicians that they might need to save the few remaining effective H. pylori drugs such as clarithromycin and amoxicillin and not use them freely for the treatment of common respiratory and urinary tract infections because of the consequences this may have on future H. pylori treatment of their patients. Or in minimum test for the absence of H. pylori in these patients and refrain from the use of effective H. pylori drugs when a patient is positive.