Therapeutic Targets
- Improvement of the symptomatology
- Protection of the duodenum and stomach, i.e., avoidance of complications.
- If necessary, elimination of Helicobacter pylori.
Therapy recommendations
- Proton pump inhibitors (PPI; acid blockers) [first-line therapy].
- Notice: Because of increasing antibiotic resistance, eradication (germ elimination) of Helicobacter pylori should preferably be accomplished with bismuth quadruple therapy Before starting treatment, risk factors for clarithromycin resistance should be determined. If not, the triple therapy with proton pump inhibitor (PPI), clarithromycin and metronidazole for 14 days, alternatively the 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 (complete elimination of a pathogen from the body). “Primary clarithromycin resistance reduces the eradication rate 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.
- First-line therapy:
- 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.
- First-line therapy:
- No
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.
- Resistance to clarithromycin (CLA) and metronidazole (MET) is the greatest risk factor for failed eradication (complete elimination of a pathogen from the body). “Primary clarithromycin resistance reduces the eradication rate 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):
- In cases of bleeding ulcer (ulcer), a combination of high-dose omeprazole (up to 200 mg/d), metronidazole, and amoxicillin should be performed
- Stress ulcer prophylaxis (prevention of stress ulcer) in critically ill patients with proton pump inhibitor (1st choice), H2 blocker or sucralfate (2nd choice).
- See also under “Further therapy”.
Helicobacter pylori eradication according to recommendation grades [S2k guideline].
- Shall
- Peptic ulcer/ulcer ventriculi (gastric ulcer) or duodeni (duodenal ulcer) with Helicobacter detection.
- Before acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs) with ulcer history (occurrence of an ulcer (gastrointestinal ulcer) in the medical history).
- 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/gastrointestinal tract); MALT lymphomas are highly favored in their development by chronic infections with the bacterium Helicobacter pylori, resp. 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 (lack of platelets < 150,000/μl), with no apparent cause.
- Should
- Asymptomatic gastritis (gastritis).
- Lymphocytic gastritis
- Gastric carcinoma prophylaxis/ 1st degree family members of persons with gastric carcinoma/ n. early gastric carcinoma.
- Ménétrier’s disease (synonyms: hypertrophic gastropathy Ménétrier, Ménétrier’s giant wrinkled gastritis): often an infection with Helicobacter pylori is found as an accompanying finding.
- May
- Iron deficiency anemia, unexplained
- Diffuse large B-cell lymphoma.
- Functional dyspepsia (irritable stomach after esophageal-gastro-duodenoscopy).
Other notes
- Treatment to eradicate (completely eliminate the pathogen) Helicobacter pylori may prevent gastric cancer in the long term.
- 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 history. 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.
Agents (main indication)
Proton pump inhibitors (PPI; proton pump inhibitors).
| Active ingredients | Special features |
| Esomeprazole | In hepatic insufficiency, 20 mg/d max. |
| 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 for renal/liver insufficiency |
- Mode of action: irreversibly inhibit the enzyme H-K-ATPase by covalent bonding.
- Proton pump inhibitors are prodrugs → are activated only in an acidic environment
- Dosing Instructions: Ideally, PPI should be taken 15-30 minutes before a meal.
- If Helicobacter pylori is detected, combination with amixocillin and clarithromycin + doubling the dose of proton pump inhibitor.
- Side effects: gastrointestinal (nausea, flatulence, diarrhea, constipation), hypergastrinemia, pruritus, alopecia, photosensitivity, hyperhidrosis, muscle, joint pain, fatigue, headache, hearing, visual disturbances.
Indications of proton pump inhibitors.
- Gastropathy due to NSAIDs
- Helicobacter pylori eradication (see gastritis/pharmacotherapy for details).
- NSAID ulcer prophylaxis in high-risk patients.
- Age > 70 years
- Ulcer in the previous disease
- 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
- Stress ulcer prophylaxis?
- Duodenal ulcer
- Ventriculi ulcer
- Zollinger-Ellison syndrome
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 |
- Mode of action: Acid secretion in the stomach ↓
- Side effects: gastrointestinal (nausea, diarrhea), liver enzymes ↑ (ALT, AST); cimetidine antiandrogenic! → No recommendation for cimetidine
- Clearly inferior to proton pump inhibitors!
Other indications
- Reflux esophagitis
- Duodenal ulcer
- Zollinger-Ellison syndrome
Other therapeutic options
- Sucralfate – forms a physicochemical barrier in the stomach; standard dose 4 x 1g/d.
- Bismuth preparations – rather rarely used in Germany.
- Prostaglandin analogues – misoprostol; promotes mucosal protection and healing; standard dose 4 x 200 μg/d.
- Note: all treatment options are clearly inferior to PPIs.
Helicobacter pylori eradication.
Standard triple therapy (French) – first-line therapy.
| Agents | Duration |
Proton pump inhibitors:
|
(7-)14 days* |
Antibiosis with
|
Standard triple therapy (Italian) – first-line therapy.
| Agents | Duration |
Proton pump inhibitors:
|
(7-)14 days* |
Antibiosis with
|
Bismuth quadruple therapy-first- or second-line therapy.
| Agents | Duration |
Proton pump inhibitors:
|
14 days |
Antibiosis with
|
|
| Bismuth |
Concomitant quadruple therapy-first-line therapy.
| Agents | Duration |
Proton pump inhibitors:
|
7 days |
Antibiosis with
|
Fluoroquinolone triple therapy – second-line therapy.
| Agents | Duration |
Proton pump inhibitor
|
10 days |
Antibiosis with
|