Helicobacter Pylori Infection: Drug Therapy

Therapeutic targets

Therapy recommendations

  • Notice: Because of increasing antibiotic resistance, eradication of Helicobacter pylori should preferably be accomplished with bismuth quadruple therapy Prior to initiation of treatment, risk factors for clarithromycin resistance should be determined. If not, triple therapy with proton pump inhibitor (PPI), clarithromycin and metronidazole for 14 days, alternatively 10-day bismuth quadruple therapy.
  • Helicobacter pylori eradication (germ elimination; indications: see below):
    • Resistance to clarithromycin (CLA) and metronidazole (MET) is the greatest risk factor for failed eradication. “Primary clarithromycin resistance reduces the eradication rate (number of cases in which therapy results in complete eradication of a pathogen) of first-line therapy with standard triple therapy with clarithromycin and amoxicillin by 66% and that of standard triple therapy with clarithromycin and metronidazole by 35%”.Quadruple therapy regimens have eradication rates around and above 90%.Risk factors for clarithromycin resistance present: (Risk factors: Origin from Southern or Eastern Europe and previous treatment with macrolide antibiotics/macrolides).
      • No
        • First-line therapy:
          • Standard triple therapy (with a PPI, clarithromycin, and amoxicillin or metronidazole) if there is a low likelihood of resistance to clarithromycin, or bismuth-based quadruple therapy (bismuth plus metronidazole plus tetracycline combined with omeprazole)
          • If the risk of resistance is low, 14-day triple therapy is more promising than the previous standard of 7-day triple therapy
        • Second-line therapy:
          • Bismuth-based quadruple therapy or fluoroquinolone triple therapy.
        • Third-line therapy: based on resistance testing.
      • Yes
        • First-line therapy:
          • If there is a high probability of primary clarithromycin resistance, bismuth-based quadruple therapy or combined (“concomitant”) quadruple therapy should be used in first-line therapy
        • Second-line therapy:
          • Fluroquinolone triple therapy
        • Third-line therapy: based on resistance testing.
  • Proton pump inhibitors (PPI; acid blockers).
  • Notice:
    • Therapy failure: if treatment has failed twice, further therapy is recommended based on resistance testing. Third-line therapy should then be antibiogram-guided. There is virtually no development of resistance to amoxicillin, so it can be used in all lines of therapy.
    • Follow-up: The success of therapy should be checked at the earliest four weeks after the end of therapy. At least two weeks before testing, treatment with proton pump inhibitors (PPI) should also be discontinued.The non-invasive testing procedures such as the 13C breath test or a stool antigen test can be used to monitor success if there is no endoscopy indication for clinical reasons.
  • See also under “Further therapy”.

Indications Helicobacter pylori eradication according to recommendation grades [S2k guideline].

  • Shall
    • Peptic ulcer/ventriculi or duodeni ulcer with Helicobacter detection.
    • Before acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs) with history of ulceration.
    • Upper gastrointestinal (GI) bleeding while taking ASA or nonsteroidal anti-inflammatory drugs (NSAIDs)
    • Low-malignant MALT lymphoma (lymphomas of mucosa-associated lymphoid tissue, MALT); so-called extranodal lymphomas; about 50% of all MALT lymphomas are diagnosed in the stomach (80% in the gastrointestinal tract); MALT lymphomas are highly favored in their development by chronic infections with the bacterium Helicobacter pylori or favored by inflammation (90% of MALT lymphomas of the stomach are Helicobacter pylori-positive); by an Erdikationstherapie (antibiotic therapy) disappear not only the bacteria, but as a result in 75% of cases also the gastric lymphoma.
    • Idiopathic thrombocytopenic purpura (ITP) – thrombocytopenia without an identifiable cause.
  • Should
    • Asymptomatic gastritis (gastritis).
    • Lymphocytic gastritis
    • Gastric cancer prophylaxis/family members 1st degree of persons with gastric cancer (stomach cancer)/Z. n. gastric early carcinoma.
    • Ménétrier’s disease (synonyms: hypertrophic gastropathy Ménétrier, Ménétrier’s giant wrinkled gastritis): frequently an infection with Helicobacter pylori is found as an accompanying finding
  • May

Other notes

  • Treatment for Helicobacter pylori eradication may prevent gastric cancer in the long term. Consideration should be given to the following high-risk individuals/constellations in whom Helicobacter pylori eradication should be performed:
    • First-degree relatives of gastric cancer patients.
    • Previous gastric neoplasms (gastric neoplasms)
    • High-risk gastritis (pangastritis (chronic form of gastritis (inflammation of the gastric mucosa) that extends to the entire stomach) or corpus-dominant gastritis/gastritis that is confined to the body of the stomach)
    • Atrophy and or/intestinal metaplasia (i.e., the normal mucosa is replaced by mucosa partially or completely corresponding to the structure of the mucosa of the small or large intestine)
  • Eradication of Helicobacter pylori can be complicated by common clarithromycin (CLA) resistance in countries of origin. More than 20% of immigrants from southeastern Europe and Turkey already show resistance to this antibiotic. Resistance rates of over 20% are now also known from Austria, Portugal, Italy and Greece.
  • In a cohort study that focused on outpatient clarithromycin-containing H. pylori eradication therapy, data from 66,559 patients were analyzed. 1824 patients developed a neuropsychiatric event (eg, delirium, anxiety, hallucinations, or manic episodes) between days 1 and 14 after initiation of therapy. This was increased by a good fourfold compared with baseline before the start of therapy (incidence rate ratio, IRR = 4.12; equivalent to 35 events per 72 person-years).
  • In pregnancy, Italian triple therapy should be preferred to French triple therapy
  • Notice: After successful Helicobacter pylori eradication, sustained therapy with a proton pump inhibitor (PPI; acid blocker) resulted in a 2.44-fold increased risk (95 percent confidence interval: 1.42-4.20) of gastric cancer.
  • Caveat. The U.S. Food and Drug Administration advises caution in prescribing the antibiotic clarithromycin in patients with cardiac (heart-related) preexisting conditions. Results of a 10-year follow-up after 2-week treatment with clarithromycin showed increased all-cause mortality (hazard ratio 1.10; 1.00-1.21), and the rate of cerebrovascular disease (hazard ratio 1.19; 1.02-1.38) was also increased.
  • Rate of Helicobacter pylori resistant to clarithromycin is increasing: In 2018, the proportion of germs resistant to the antibiotic was 22%.

Helicobacter pylori eradication.

Standard triple therapy (French) – first-line therapy.

Agents Duration
Proton pump inhibitors:

  • Esomeprazole, omeprazole, rabeprazole, or
  • Lansoprazole or
  • Pantoprazole
 (7-)14 days*
Antibiosis with

  • Clarithromycin* and
  • Amoxicillin

Standard triple therapy (Italian) – first-line therapy.

Agents Duration
Proton pump inhibitors:

  • Esomeprazole, omeprazole, rabeprazole, or
  • Lansoprazole or
  • Pantoprazole
 (7-)14 days*
Antibiosis with

  • Clarithromycin* and
  • Metronidazole

Bismuth quadruple therapy-first- or second-line therapy.

Agents Duration
Proton pump inhibitors:

  • Esomeprazole, omeprazole, rabeprazole, or
  • Lansoprazole or
  • Pantoprazole
 14 days
Antibiosis with

  • Tetracycline
  • Metronidazole
Bismuth

Concomitant quadruple therapy-first-line therapy.

Agents Duration
Proton pump inhibitors:

  • Esomeprazole, omeprazole, rabeprazole, or
  • Lansoprazole or
  • Pantoprazole
 7 days
Antibiosis with

  • Clarithromycin*
  • Amoxicillin
  • Metronidazole

Fluoroquinolone triple therapy – second-line therapy.

Agents Duration
Proton pump inhibitor

  • Esomeprazole
 10 days
Antibiosis with

  • Amoxicillin
  • Fluoroquinolone

Active ingredients (main indication)

Proton pump inhibitors (PPI; proton pump inhibitors).

Active ingredients Special features
Esomeprazole In hepatic insufficiency, max. 20 mg/d
Lansoprazole Metabolized via cytochrome P450In renal/liver failure max 30 mg/d.
Omeprazole Metabolized via cytochrome P450In renal/hepatic insufficiency max 20/10 mg/d (p.o./i.v.)
Pantoprazole In renal insufficiency, max. 40 mg/dIn hepatic insufficiency, max. 20 mg/d
Rabeprazole No dose adjustment in renal/liver failure.

Indications of proton pump inhibitors.

  • Gastropathy (stomach disease) caused by NSAIDs (nonsteroidal anti-inflammatory drugs).
  • Helicobacter pylori eradication (see gastritis/pharmacotherapy for details).
  • NSAID ulcer prophylaxis in high-risk patients.
    • Age > 70 years
    • Ulcer (ulcer) in the previous illness
    • Taking multiple NSAIDs (including acetylsalicylic acid (ASA))
    • NSAID high-dose therapy
    • Comedication with anticoagulants
    • H. pylori infection
    • Comedication with steroids
    • Comedication with serotonin reuptake inhibitors (SSRI)
  • Reflux esophagitis (esophagitis due to reflux).
  • Stress ulcer prophylaxis?
  • Duodenal ulcer (duodenal ulcer).
  • Ulcus ventriculi (gastric ulcer)
  • Zollinger-Ellison syndrome – neoplasia (neoplasm) leading to increased gastrin production and therefore also called gastrinoma.

H2 antihistamines

Active ingredients Special features
Cimetidine Dose adjustment in severe renal insufficiency
Ranitidine Dose adjustment in severe renal insufficiency
Roxatidine Dose adjustment in renal insufficiencyKI in severe renal/hepatic insufficiency.
Famotidine Dose adjustment in renal/liver insufficiency.
Nizatidine Dose adjustment in severe renal insufficiency.

Other therapeutic options

  • Sucralfate – forms a physicochemical barrier in the stomach.
  • Bismuth preparations – rather rarely used in Germany.
  • Prostaglandin analogues – misoprostol; promotes mucosal protection and healing.
  • Note: all treatment options are clearly inferior to PPIs.