TREATMENT Helicobacter pylori Infection INDICATIONS
The most clear-cut indications for treatment are H. pylori–related duodenal or gastric ulceration or low-grade gastric B-cell lymphoma. Whether or not the ulcers are currently active, H. pylori should be eradicated in patients with documented ulcer disease to prevent relapse (Fig. 60-2). Testing for H. pylori and treatment if the results are positive also have been advocated in uninvestigated simple dyspepsia, but only when the prevalence of H. pylori in the community is >20% are these measures more cost-effective than simply treating the dyspepsia with PPIs. Guidelines have recommended H. pylori treatment in functional dyspepsia in case the patient is one of the perhaps 0–7% who will benefit from such treatment (beyond placebo effects). Some guidelines also recommend treatment of conditions not definitively known to respond to H. pylori eradication, including idiopathic thrombocytopenic purpura, vitamin B12 deficiency, and iron-deficiency anemia (in the last instance, only when other causes have been carefully excluded). Test-and-treat has emerged as a common clinical practice in recent years despite the lack of direct evidence that it is advantageous; whether this practice will survive the scrutiny of time and further study remains to be determined. For individuals with a strong family history of gastric cancer, treatment to eradicate H. pylori in the hope of reducing their cancer risk is reasonable but of unproven value. Currently, widespread community screening for and treatment of H. pylori as primary prophylaxis for gastric cancer and peptic ulcers are not recommended in most countries, mainly because the extent of the consequent reduction in cancer risk is not known. Several studies have found a modestly reduced cancer risk after treatment, but the period of follow-up is still fairly short and the size of the effect in different populations remains unclear. Other reasons not to treat H. pylori in asymptomatic populations at present include (1) the adverse side effects (which are common and can be severe in rare cases) of the multiple-antibiotic regimens used; (2) antibiotic resistance, which may emerge in H. pylori or other incidentally carried bacteria; (3) the anxiety that may arise in otherwise healthy people, especially if treatment is unsuccessful; and (4) the 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. Despite the absence of screening strategies, many doctors treat H. pylori if it is known to be present (particularly in children and younger adults), even when the patient is asymptomatic. The rationale is that it reduces patient concern and may reduce future gastric cancer risk and that any reduction in risk is likely to be greater in younger patients. However, such practices do not factor in any potential benefits of H. pylori colonization. Overall, despite widespread clinical activity in this area, most treatment of asymptomatic H. pylori carriage is given without a firm evidence base. REGIMENS
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 prompted the development of multidrug regimens, the most successful of which are triple and quadruple combinations. Current regimens consist of a PPI and two or three antimicrobial agents given for 7–14 days (Table 60-2). Research on optimizing drug combinations to increase efficacy continues, and guidelines are likely to change as the field develops and as countries increasingly tailor treatment to suit local antibiotic resistance patterns and economic needs.
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. Increasing levels of H. pylori resistance to clarithromycin, quinolones, and—to a lesser extent—metronidazole are of growing concern and are thought to be responsible for the reduced efficacy of previously popular clarithromycin-based triple-therapy regimens worldwide. Treatment with these regimens is now virtually confined to certain northern European countries where the use of clarithromycin (or azithromycin) for respiratory infections has not been widespread and resistance rates in H. pylori are still low. Strains of H. pylori with some degree of in vitro resistance to metronidazole are common but still may be eradicated with metronidazole-containing regimens, which have only slightly reduced efficacy in vivo. 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, the patient’s history of (even distant) antibiotic use for other conditions should be ascertained; use of the previously administered agent(s) should then be avoided if possible, particularly in the case of clarithromycin (e.g., previous use for upper respiratory infection) and quinolones. If initial H. pylori treatment fails, the usual approach is empirical re-treatment with another drug regimen (Table 60-2). The third-line approach should ideally be endoscopy, biopsy, and culture plus treatment based on documented antibiotic sensitivities. However, empirical third-line therapies are often used.
Non-pylori gastric helicobacters are treated in the same way as H. pylori. However, in the absence of trials, it is unclear whether a positive outcome always represents successful treatment or whether it is sometimes due to natural clearance of the bacteria.