Helicobacter Pylori: Recommended Eradication Regimens

Helicobacter pylori is a gram-negative organism that induces gastric infection. The infection causes chronic gastritis and may lead to peptic ulcer disease (PUD). H pylori is also associated with gastric adenocarcinoma and low-grade gastric lymphoma, referred to as mucosa-associated lymphoid tissue (MALT) lymphoma.^1,2 Although H pylori infection is more common in developing countries than in industrialized countries, up to 30%-40% of the total US population is infected with this bacterium.^3,4 This condition is most commonly seen in blacks, Hispanics, and Asians.^1,5 There is an increased prevalence of H pylori with age, such that by age 60, approximately 50% of persons in this country are infected.^1,5,6

Person-to-person transmission of H pylori occurs via one of three pathways: fecal–oral, oral–oral, or iatrogenic.^2,5,6 Fecal–oral transmission of H pylori is theorized to occur directly or indirectly from feces-contaminated water or food; oral–oral transmission is presupposed based on isolation of H pylori from the oral cavity; and iatrogenic transmission can occur through use of infected diagnostic instruments such as endoscopes.2,5,6 Unclean water, consumption of raw vegetables, crowded living conditions, and a large number of children are all risk factors for person-to-person transmission of H pylori infection.^2,5

Persons with H pylori infection may be asymptomatic or experience varying degrees of dyspepsia.¹ In typical cases, H pylori causes chronic gastritis; if the infection remains untreated over a period of 20-40 years, atrophic gastritis and gastric cancer may develop.² H pylori can disrupt the architecture of the gastroduodenal mucosa, which can cause ulcers.⁷ Most non–NSAID-related ulcers are infected with H pylori; eradicating the bacteria markedly decreases ulcer recurrence.^5,8 An H pylori-induced peptic ulcer, compared with an NSAID-induced peptic ulcer, affects the duodenum to a greater extent than the stomach, usually causes epigastric pain, and produces less severe gastrointestinal bleeding.²

Serologic tests are used for initial diagnosis of H pylori infection; for confirmation of cure (ie, to confirm eradication of the organism), a urea breath test or stool antigen assay is utilized.¹ Screening asymptomatic patients for H pylori is not warranted.¹ Endoscopy is not recommended solely for diagnosis of H pylori infection, although this procedure is utilized if is indicated for other reasons.¹

Eradication of H pylori is recommended in patients with complications such as gastritis, ulcer, or malignancy, and it can even cure some cases of MALT lymphoma (although not other infection-related malignancies).^1,2 Eradication of H pylori has been shown to decrease recurrent PUD-related bleeding.⁹ Although the treatment of asymptomatic infection has been controversial, the recognition of the association between H pylori infection and cancer has led to a recommendation for such treatment.¹
 
Treatment entails eradication regimens. Table 1 outlines first-line eradication regimens and other recommendations from the updated guideline for the management of H pylori infection by Chey, Wong, and the Practice Parameters Committee and Governing Board of the American College of Gastroenterology (ACG).³ This 2007 guideline updates the previous guideline, last published in 1998.³ 

Eradication regimens consist of multiple drug therapy.^2,3,10,11 A combination of an antisecretory agent, usually a proton pump inhibitor (PPI), plus two antibiotics (triple therapy) or a regimen consisting of a bismuth salt, two antibiotics, and an antisecretory agent (quadruple therapy) is recommended.^1,2 Use of such combinations increases eradication rates and reduces the risk for antibiotic resistance.² Both options are effective. Although quadruple therapy is more cumbersome, it is a reasonable option for use in penicillin-allergic patients (see Comments in Table 1).^1,3

A recent meta-analysis reports data suggesting that twice-daily dosing of a PPI in clarithromycin-based triple regimens is more effective than once-daily dosing.^3,12 PPIs are taken 30-60 minutes before eating to optimize their effects on gastric acid secretion.³ If a patient can not tolerate a PPI (eg, because of diarrhea), an H2-receptor antagonist (eg, ranitidine [Zantac]) can be substituted.^3,13

In the U.S., treatment durations of 10-14 days are typically used; international guidelines recommend treatment durations of ≥7 days.³ With regard to eradication rates, a 14-day regimen has been found—and confirmed—to be superior to a 7-day regimen.^3,14,15 For patients with duodenal or gastric ulcer, continuation of acid suppression (ie, PPI use) is recommended for ≥4 weeks.¹ If H pylori is not eradicated, treatment is repeated; if two courses are not successful, cultures for sensitivity testing may be obtained by endoscopy.¹

Recent research results suggest that eradication rates achieved by first-line treatment with a PPI, clarithromycin, and amoxicillin (Table 1) have fallen to 70%-85%, partly because of an increase in clarithromycin resistance: As a result, Chey et al³ recommend a 14-day course of clarithromycin triple therapy to optimize treatment. These researchers also report that several studies from Italy describe eradication rates >90% with a novel sequential therapy utilizing the antiparasitic agent tinidazole (Table 1).

At the Annual Scientific Meeting of the ACG in October 2009, a group of scientists announced the results of an open-label study testing a new quadruple therapy called LOAD, which consists of levofloxacin, omeprazole, the antiparasitic agent nitazoxanide (Alinia), and doxycycline.¹⁶ The researchers compared 10- and 7-day courses of LOAD with a 10-day course of a standard triple-therapy regimen called LAC, which consists of lansoprazole, amoxicillin, and clarithromycin. Using a stool-antigen assay 2 weeks after therapy, the research team found that the 10-day and 7-day LOAD regimens worked similarly well and were therapeutically superior to the LAC regimen in treatment-naïve patients.

Poor medication adherence and antibiotic resistance are the most important predictors of treatment failure following anti-H pylori therapy.³ Mégraud and Lamouliatte¹⁷ report that, although evidence is limited, smoking, alcohol intake, and a poor diet may reduce the likelihood of successful H pylori eradication. Development of side effects may be a contributing factor in poor medication adherence. Table 2 outlines common mild side effects associated with the individual components of the H pylori eradication regimens; reports of moderate or severe side effects are reported in only 5%-20% of patients.^3,10 Patients should be adequately counseled regarding these issues. Although beyond the scope of this column, the potential for drug–drug interactions needs to be assessed with respect to a patient’s co-morbidities and corresponding pharmaceutical care plan. NPs are encouraged to review the current literature and utilize appropriate references (eg, drug–drug interaction software) to alert them of this potential risk. 

Helicobacter pylori infection is a major cause of chronic gastritis and PUD. This bacterium can also cause gastric cancer. Eradication regimens require multi-drug therapy, typically acid suppressants plus antibiotics. NPs are encouraged to be familiar with the most up-to-date first-line regimens to optimize patients’ treatment outcomes.

Dr. Zagaria is a Senior Care Consultant Pharmacist and President of MZ Associates, Inc., in Norwich, NY.

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