Team:Ciencias-UNAM/Project

The most clear-cut indications for treatment are H. pylori–related duodenal or gastric ulceration or low-grade gastric B cell lymphoma. H. pylori should be eradicated in patients with documented ulcer disease, whether or not the ulcers are currently active, to reduce the likelihood of relapse. Many guidelines now recommend H. pylori eradication in uninvestigated simple dyspepsia following noninvasive diagnosis; others also recommend treatment in functional dyspepsia, in case the patient is one of the perhaps 7% (beyond placebo effects) to benefit from such treatment. Individuals with a strong family history of gastric cancer should be treated to eradicate H. pylori in the hope that their cancer risk will be reduced. Currently, widespread community screening for and treatment of H. pylori as primary prophylaxis for gastric cancer and peptic ulcers are not recommended, mainly because it is unclear whether treatment for H. pylori reduces the risk of cancer to that in persons who have never acquired the organism. The largest randomized controlled study to date (performed in China) showed no cancer risk reduction during the 7 years of follow-up, although a post hoc subgroup analysis documented improvement in the group of participants who did not already have gastric atrophy or intestinal metaplasia. Other studies have found a reduced cancer risk after treatment, but the size of this effect in different populations remains unclear, and the results of further large-scale prospective interventional studies must be awaited. Other reasons for not treating H. pylori in asymptomatic populations at present include:

1. The adverse side effects of the multiple-antibiotic regimens used. (which are common and can be severe in rare cases)
2. Antibiotic resistance, which may arise in H. pylori or other incidentally carried bacteria
3. The anxiety that may arise in otherwise healthy people, especially if treatment is unsuccessful.
4. The apparent existence of a subset of people who will develop GERD symptoms after treatment, although on average H. pylori treatment does not affect GERD symptoms or severity.

Although H. pylori is susceptible to a wide range of antibiotics in vitro, monotherapy is not usually successful, probably because of inadequate antibiotic delivery to the colonization niche. Failure of monotherapy has prompted the development of multidrug regimens, the most successful of which are triple and quadruple combinations. Initially these regimens produced H. pylori eradication rates of >90% in many trials; in recent years, however, resistance to key antibiotics has become more common, a trend leading to H. pylori eradication rates of only 75–80% for the most commonly used regimens. Current regimens consist of a PPI or ranitidine bismuth citrate and two or three antimicrobial agents given for 7–14 days. Research on optimizing drug combinations to increase efficacy continues, and it is likely that guidelines will change as the field develops and as countries increasingly individualize treatment to suit local antibiotic resistance patterns and economic needs [6,7]. An increasing number of infected individuals are found to harbor antibiotic-resistant bacteria. This results in initial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies, such as a quadruple therapy.[8,9]

• ^a Meta-analyses show that a 14-day course of therapy is slightly superior to a 7-day course. However, in populations where 7-day treatment is known to have very high success rates, this shorter course is still often used.
• ^b Omeprazole may be replaced with any proton pump inhibitor at an equivalent dosage or, in regimens 1 and 2, with ranitidine bismuth citrate (400 mg).
• ^c Data supporting this regimen come mainly from Europe and are based on the use of bismuth subcitrate and metronidazole (400 mg tid). This is the most commonly used second-line regimen.
• ^dData supporting this regimen come from Europe. Although the two 5-day courses of different drugs have usually been given sequentially, recent evidence suggests no added benefit from this approach. Thus 10 days of the four drugs combined may be as good and may aid compliance.
• ^e Data supporting this second- or third-line regimen come from Europe. This regimen may be less effective where rates of quinolone use are high. Theoretically, it may also be wise to avoid it in populations where Clostridium difficile infection is common after broad-spectrum antibiotic use.

The standard first-line therapy is a one week triple therapy consisting of proton pump inhibitors such as omeprazole and the antibiotics clarithromycin and amoxicillin [6,7]. Variations of the triple therapy have been developed over the years, such as using a different proton pump inhibitor, as with pantoprazole or rabeprazole [7].
The two most important factors in successful H. pylori treatment are the patient's close compliance with the regimen and the use of drugs to which the patient's strain of H. pylori has not acquired resistance. Treatment failure following minor lapses in compliance is common and often leads to acquired resistance to metronidazole or clarithromycin. To stress the importance of compliance, written instructions should be given to the patient, and minor side effects of the regimen should be explained. Resistance to clarithromycin and, to a lesser extent, to metronidazole is of growing concern. Clarithromycin resistance is less prevalent but, if present, usually results in treatment failure. Strains of H. pylori that are apparently resistant to metronidazole are more common but still may be cleared by metronidazole-containing regimens, which have only slightly reduced efficacy. Assessment of antibiotic susceptibilities before treatment would be optimal but is not usually undertaken because endoscopy and mucosal biopsy are necessary to obtain H. pylori for culture and because most microbiology laboratories are inexperienced in H. pylori culture. In the absence of susceptibility information, a history of the patient's (even distant) antibiotic use for other conditions should be obtained; use of the agent should then be avoided if possible, particularly in the case of clarithromycin (e.g., previous use for upper respiratory infection). If initial H. pylori treatment fails, one of two strategies may be used. The more common approach is empirical re-treatment with another drug regimen, usually quadruple therapy. The second approach is endoscopy, biopsy, and culture plus treatment based on documented antibiotic sensitivities. If re-treatment fails, susceptibility testing should ideally be performed, although empirical third-line therapies are often used.
Clearance of non-pylori gastric helicobacters can follow the use of bismuth compounds alone or of triple-drug regimens. However, in the absence of trials, it is unclear whether this outcome represents successful treatment or natural clearance of the bacterium

1.5 Resistance