Challenges to therapy in the future

Quadruple therapy (with a proton pump inhibitor (PPI), metronidazole, tetra cycline and bismuth) is generally reserved for second-line treatment; howev er, studies using this regimen for 7 days have found it to be effective eve n in metronidazole-resistant strains. Resistance is an ongoing problem with antimicrobial therapy but considerable progress has now been made into und erstanding the underlying genetic mechanisms of this process. Metronidazole resistance in Europe is usually in the range of 20-30% of strains but may be as high as 70% in some countries. One genetic mechanism involved is thou ght to be a mutation of the rdxA gene. Macrolide resistance appears to be o n the increase in Europe, varying from 1% in some countries to 13% in other s. The genetic mechanism involved has been shown to be a point mutation of a ribosomal RNA. Amoxicillin resistance is an emerging problem that has an adverse effect on eradication rates in clinical practice. Resistance has be en shown to be caused by the absence of one of the four binding proteins in the cell wall. Few novel antibiotics have been developed for use in eradic ation therapy, although rifabutin, secnidazole and furazolidone have shown some success as part of combination therapy. Alternative therapies that hav e been rested include mucosal protective agents which have been used in pla ce of a PPI in some eradication regimens with some success, and the somatos tatin analog, octreotide, that has been used as part of quadruple therapy i n place of a PPI and produced eradication rates of approximately 88%. The u ltimate challenge is still to develop a safe and effective vaccine against Helicobacter pylori. Current and future research will also focus on identif ying genetic targets for therapy, adhesion molecule analogs to prevent bind ing of the bacterium, and urease inhibitors. The current triple therapy tre atment options available for the eradication of Helicobacter pylori infecti on are over 90% effective in susceptible organisms and there are very few m edical conditions to which we can offer such efficacious treatment. Unfortu nately, the recommendations made at consensus conferences are not always pu t into practice and physicians in primary care may be unaware of the true e fficacy of eradication therapy. Treatment is very simple: three drugs, twic e a day for 1 week. The main focus for both primary care physicians and gas troenterologists should be to reinforce the need for patient compliance, ot herwise we will see an increase in antibiotic resistance. Patients should b e prewarned that they may experience some mild side effects and should be e ncouraged to complete the course of treatment. The real challenge for the f uture will be the management of patients who do not respond to first-line t reatment. This paper will focus on potential problems with therapy, such as antibiotic resistance, and possible future solutions, such as novel antibi otics and vaccines.