Gastritis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2] Fahad Hasan, MBBS, MD[3]

Overview

Medical therapy for gastritis depends on its specific cause. Medications known to cause gastritis such as NSAIDs (aspirin, naproxen, ibuprofen) should be discontinued. Smoking cessation and abstinence from alcohol consumption are recommended. Medications to decrease gastric acid production such as proton pump inhibitors (PPI) are recommended. In cases of Helicobacter pylori infection, antimicrobial drugs are required for eradication. The 2024 American College of Gastroenterology (ACG) Clinical Guideline and the 2022 Maastricht VI/Florence Consensus Report represent the most current authoritative statements on H. pylori management and form the evidence base for contemporary recommendations.

A key paradigm shift in contemporary guidelines is the removal of clarithromycin-based triple therapy as an empiric first-line option in most populations, replaced by optimized bismuth quadruple therapy (BQT) as the preferred first-line regimen in treatment-naïve patients. Newer options including vonoprazan (a potassium-competitive acid blocker, PCAB)-based therapy and rifabutin-based triple therapy are now recognized as alternative first-line regimens. Indications for treatment of H. pylori infection include past or present duodenal and/or gastric ulcer, with or without complications; following resection of gastric cancer; gastric mucosa-associated lymphoid tissue (MALT) lymphoma; atrophic gastritis; dyspepsia; patients with first-degree relatives with gastric cancer; and at the patient's wishes. The 2024 ACG guideline additionally recommends expanding testing and treatment to individuals at increased risk for gastric adenocarcinoma, including those with autoimmune gastritis, gastric intestinal metaplasia, and household contacts of patients with confirmed H. pylori infection on non-serologic testing.

Factors involved in choosing treatment regimens include:

• Prevalence of H. pylori infection
• Prevalence of gastric cancer
• Regional resistance to antibiotics (especially clarithromycin and levofloxacin)
• Availability of bismuth compounds
• Cost of tests
• Availability of endoscopy and H. pylori tests, including antibiotic susceptibility testing
• Ethnicity
• Drug allergies and tolerance (particularly penicillin allergy)
• Previous treatments and outcome
• Ease of administration
• Adverse effects
• Effectiveness of local treatment
• Recommended dosages and treatment duration

Medical Therapy

Medical therapy for gastritis depends on its specific cause.

• Medications known to cause gastritis such as NSAIDs (aspirin, naproxen, ibuprofen) should be discontinued.
• Abstinence from alcohol consumption is recommended.
• Medications to neutralize stomach acid or decrease its production usually help in eliminating the symptoms and promote healing.
• Gastritis caused by pernicious anemia is treated with vitamin B12.
• Gastritis due to stress is best treated by prevention. Medications to decrease gastric acid production such as proton pump inhibitors (PPI) are recommended for critically ill hospitalized patients.
• In cases of Helicobacter pylori infection, antimicrobial drugs are required. H. pylori infection is now classified as an infectious disease in the ICD-11, and in principle all infected patients should receive treatment.
• For patients testing negative for H. pylori with dyspepsia, empiric PPI therapy is recommended as first-line pharmacological management. Patients who do not respond may be considered for prokinetic agents or low-dose tricyclic antidepressants.

Indications for H. pylori eradication treatment include:

• Past or present duodenal and/or gastric ulcer, with or without complications
• Following resection of gastric cancer
• Gastric mucosa-associated lymphoid tissue (MALT) lymphoma
• Atrophic gastritis
• Dyspepsia
• Patients with first-degree relatives with gastric cancer
• Patients at increased risk for gastric adenocarcinoma (including those with autoimmune gastritis or gastric intestinal metaplasia)
• Household contacts of patients with confirmed H. pylori (non-serologic test)
• Patient's wishes

General Principles of H. pylori Eradication

Maintenance of adequate intragastric acid suppression is critical for successful H. pylori eradication, as elevated intragastric pH promotes active bacterial replication and enhances antibiotic bactericidal activity. H2-receptor antagonists are not adequate for this purpose and are not recommended as the acid-suppressive backbone for any eradication regimen. All eradication regimens should be administered for 14 days; shorter durations are associated with meaningfully lower eradication rates.

Antibiotic stewardship principles must guide regimen selection. Clarithromycin resistance has risen to 17–27% globally and levofloxacin resistance is increasing rapidly in many regions, rendering empiric use of clarithromycin-based triple therapy and empiric levofloxacin-based therapy no longer appropriate as standard first-line approaches. Where molecular or culture-based antibiotic susceptibility testing (AST) is available, susceptibility-guided therapy is the preferred strategy per the 2022 Maastricht VI consensus.

First-Line Regimens for Treatment-Naïve Patients

Key 2024 ACG guideline change: Clarithromycin-based PPI triple therapy (PPI + clarithromycin + amoxicillin or metronidazole) is no longer recommended as empiric first-line therapy. It should only be used if antibiotic susceptibility testing has confirmed clarithromycin sensitivity. Eradication rates with PPI-clarithromycin triple therapy drop to approximately 30% in clarithromycin-resistant H. pylori strains. Concomitant therapy (PPI + amoxicillin + clarithromycin + metronidazole simultaneously) has also been removed as a first-line recommendation by the 2024 ACG guideline, though it retains a role in some international guidelines in regions with low dual clarithromycin and metronidazole resistance.

Regimen	Medications and Dosing	Duration	ACG 2024 Recommendation (GRADE)	Comments
Optimized Bismuth Quadruple Therapy (BQT) (Preferred first-line)	PPI b.i.d. + tetracycline 500 mg q.i.d. + metronidazole 500 mg t.i.d.–q.i.d. + bismuth subcitrate or bismuth subsalicylate q.i.d.	14 days	Strong recommendation; moderate quality evidence	Doxycycline must NOT be substituted for tetracycline (10–17% lower eradication rate). Metronidazole 500 mg preferred over 250 mg (better overcomes partial resistance). All components must be dosed at full frequency and dose.
Rifabutin-Based Triple Therapy (Alternative first-line; RHB-105/Talicia®)	Omeprazole 40 mg + amoxicillin 1000 mg + rifabutin 50 mg; all three dosed every 8 hours (t.i.d.)	14 days	Conditional recommendation; low quality evidence	Phase 3 ERADICATE Hp2 trial: eradication rate 83.8% (95% CI 78.4–88.0%) vs. 57.7% comparator (P<0.001). Efficacy not significantly impacted by clarithromycin, amoxicillin or multi-drug resistance. Monitor CBC for myelosuppression.
PCAB (Vonoprazan)–Amoxicillin Dual Therapy (Alternative first-line)	Vonoprazan 20 mg b.i.d. + amoxicillin 1 g t.i.d.	14 days	Conditional recommendation; moderate quality evidence	Superior to lansoprazole triple therapy overall (77.2% vs. 68.5%; P=0.013) and markedly superior in clarithromycin-resistant strains (69.6% vs. 31.9%). FDA approved in US.
PCAB (Vonoprazan)–Amoxicillin–Clarithromycin Triple Therapy (Alternative first-line; preferred over PPI triple when clarithromycin sensitivity unknown)	Vonoprazan 20 mg b.i.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d.	14 days	Conditional recommendation; moderate quality evidence	Eradication 80.8% overall and 65.8% in clarithromycin-resistant infections vs. 31.9% with lansoprazole triple (superior; P<0.001). FDA approved in US.
PPI-clarithromycin triple therapy (Only if susceptibility-confirmed)	Standard dose PPI b.i.d. + clarithromycin 500 mg b.i.d. + amoxicillin 1 g b.i.d. (or metronidazole 500 mg b.i.d. if penicillin allergy)	14 days	Not recommended empirically (Key Concept, expert consensus)	Use only when AST confirms clarithromycin sensitivity. No longer first-line per ACG 2024 or Maastricht VI 2022 for empiric use.
PPI = proton pump inhibitor; PCAB = potassium-competitive acid blocker; b.i.d. = twice daily; t.i.d. = three times daily; q.i.d. = four times daily; AST = antibiotic susceptibility testing; CBC = complete blood count. Standard PPI doses: lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, rabeprazole 20 mg, esomeprazole 40 mg.

Vonoprazan-Based Therapy

Vonoprazan (a potassium-competitive acid blocker) provides more potent and sustained intragastric acid suppression than conventional PPIs, independent of CYP2C19 genotype. In the pivotal phase 3 VOCAL trial (n=1,046 treatment-naïve patients), vonoprazan triple therapy (20 mg b.i.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. × 14 days) achieved eradication rates of 84.7% vs. 78.8% with lansoprazole triple therapy in non-resistant strains (non-inferior; difference 5.9%, 95% CI −0.8 to 12.6; P<0.001). In clarithromycin-resistant infections, vonoprazan triple therapy achieved 65.8% eradication compared to 31.9% with lansoprazole triple (difference 33.9%, 95% CI 17.7–48.1; P<0.001). Vonoprazan dual therapy achieved 69.6% eradication in clarithromycin-resistant strains vs. 31.9% with lansoprazole triple (difference 37.7%, 95% CI 20.5–52.6; P<0.001). A systematic meta-analysis of 13 RCTs (n=4,023) confirmed vonoprazan–amoxicillin high-dose dual therapy ITT eradication rate of 88.81% and per-protocol rate of 93.56%, with significantly fewer adverse events (14.56% vs. 26.00%; RR=0.57, 95% CI 0.48–0.67; P<0.0001).

Rifabutin-Based Triple Therapy

The combination product RHB-105 (Talicia®) containing omeprazole 40 mg, amoxicillin 1000 mg, and rifabutin 50 mg administered every 8 hours for 14 days achieved H. pylori eradication of 83.8% (95% CI 78.4–88.0%; P<0.001) in the phase 3 ERADICATE Hp2 double-blind trial (n=455 treatment-naïve US patients). Efficacy was not significantly affected by clarithromycin, amoxicillin, or multi-drug resistance. Adverse effects include diarrhea (12.7%), headache (11.9%), and chromaturia (9.3%); no leukopenia was observed in this trial. Rifabutin has potential for myelosuppression (myelotoxicity) and ocular toxicity; complete blood count monitoring is recommended. As a second-line antituberculous agent, its use for H. pylori requires careful consideration in settings with endemic tuberculosis to minimize the risk of promoting rifamycin resistance.

Predictors of H. pylori Treatment Outcome

Predictors of treatment failure include:

• Poor compliance with the regimen
• Antibiotic resistance (the key factor in eradication failure and recurrence of H. pylori infection), particularly to clarithromycin, levofloxacin, and metronidazole
• Bacterial factors: CagA-negative strains are at increased risk of treatment failure compared with CagA-positive strains
• CYP2C19 polymorphisms may influence treatment outcomes when regimens containing PPIs are used, as they influence PPI clearance and thus intragastric acid suppression (this effect is largely overcome by vonoprazan, which is not CYP2C19-dependent)
• Smoking and heavy alcohol use are associated with lower eradication rates
• High bacterial load before treatment

Drug	Common Side Effects	Recommendations / Notes
Proton pump inhibitors (PPIs)	Headache Diarrhea Hypomagnesemia with long-term use Increased risk of C. difficile infection with long-term use	PPIs should be taken 30–60 min before eating to optimize effect on gastric acid secretion. CYP2C19 metabolism affects inter-individual variability in acid suppression. Deprescribe if no ongoing indication after completion of therapy.
Vonoprazan (PCAB)	Diarrhea Nausea	Superior and CYP2C19-independent acid suppression vs. PPIs. Dose: 20 mg b.i.d. for eradication regimens. Not widely available outside US, Japan, and limited other markets.
Clarithromycin	GI upset Headache Altered taste QT prolongation at high doses	Use only when AST confirms susceptibility. Do not use empirically given ≥15–20% regional resistance rates in most populations. Cross-resistance with other macrolide antibiotics.
Amoxicillin	GI upset Headache Diarrhea Hypersensitivity / anaphylaxis	Contraindicated in confirmed penicillin allergy. Allergy reassessment (penicillin skin testing) should be considered, as true penicillin allergy is frequently overreported.
Metronidazole	Metallic taste in the mouth Dyspepsia A disulfiram-like reaction with alcohol consumption	Partial resistance may be overcome by using higher doses (500 mg t.i.d.–q.i.d.) and longer treatment duration (14 days) in bismuth quadruple regimens.
Tetracycline	GI upset Photosensitivity Esophageal irritation if not swallowed correctly	Must not be substituted by doxycycline in BQT (10–17% lower eradication rate). Tetracyclines must not be given to children under 8 years of age due to tooth discoloration, and are contraindicated in pregnancy.
Bismuth compounds	Darkening of tongue and stool Nausea GI upset	Available as bismuth subcitrate or bismuth subsalicylate. Dose at full q.i.d. frequency for optimization of BQT.
Rifabutin	Rash Nausea, vomiting, dyspepsia Diarrhea Myelotoxicity (leukopenia) Ocular toxicity (uveitis) Chromaturia (orange discoloration of body fluids)	Monitor CBC. Use with caution in settings with endemic TB (risk of rifamycin resistance). Risk of myelosuppression is low at standard doses used in H. pylori regimens (50 mg t.i.d. as RHB-105).

Salvage Therapy for Persistent H. pylori Infection

In patients with persistent H. pylori infection, every effort should be made to avoid antibiotics that have previously been used by the patient. All salvage regimens should be given for 14 days.

Clinical Scenario	Preferred Salvage Regimen	Eradication Rate	Comments
Failed initial PPI-clarithromycin triple therapy	Optimized BQT (PPI b.i.d. + tetracycline 500 mg q.i.d. + metronidazole 500 mg t.i.d.–q.i.d. + bismuth q.i.d.) × 14 days	75–90%	Standard salvage per ACG 2024. Effective regardless of clarithromycin resistance.
Failed optimized BQT	Rifabutin triple therapy (PPI + amoxicillin + rifabutin) × 14 days; OR susceptibility-guided therapy	89.0% ITT (rifabutin arm); 94.0% per-protocol in RCT vs. BQT rescue	In a multicenter RCT, rifabutin triple therapy was non-inferior to BQT as rescue, with higher compliance and fewer adverse events.
Failed optimized BQT AND rifabutin therapy	Antibiotic susceptibility testing (AST) strongly recommended; levofloxacin triple therapy (PPI + amoxicillin + levofloxacin × 14 days) only if levofloxacin-sensitive strain confirmed	87% (levofloxacin-susceptible strains, 10–14 days)	Levofloxacin empiric use is not recommended given rapidly rising fluoroquinolone resistance (>30% in some Asian populations). Culture-based or PCR-based AST from endoscopic biopsy required.
≥2 prior treatment failures	AST-guided therapy; specialist gastroenterology referral	Variable	ACG 2024 strongly recommends AST to guide all further regimen selection after 2 failures.

Levofloxacin: Levofloxacin-based triple therapy (PPI, levofloxacin, and amoxicillin) can be used as second- or third-line therapy in patients with persistent H. pylori infection when levofloxacin susceptibility is confirmed by AST. Empiric levofloxacin use is not recommended by the 2024 ACG guideline due to rapidly rising fluoroquinolone resistance rates globally.

Furazolidone (see also the Developing Countries section below): Furazolidone is an alternative to clarithromycin, metronidazole, or amoxicillin in certain geographic areas where it is available. Furazolidone is not available in the United States or United Kingdom. Adverse effects include nausea, vomiting, headache and malaise; rare but serious risks include hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) and monoamine oxidase (MAO) inhibitor-type interactions requiring dietary tyramine restriction.

Penicillin Allergy

In patients with confirmed penicillin allergy, amoxicillin-containing regimens should be avoided. Optimized BQT (which does not require amoxicillin) is the preferred first-line regimen. If BQT is unavailable or has failed, PPI + clarithromycin + metronidazole (triple therapy) for 14 days may be considered as an alternative, with awareness of clarithromycin resistance limitations. Penicillin allergy evaluation and penicillin skin testing should be considered, as true penicillin allergy is frequently overreported; many patients with a label of penicillin allergy can safely receive amoxicillin after formal evaluation.

Non-H. pylori Gastritis: Acid Suppression

For patients with reactive gastropathy or chemical gastropathy related to NSAIDs, bile reflux, or other injury, discontinuation of the offending agent plus PPI therapy is the primary approach. Standard-dose PPI therapy once daily for 4–8 weeks is effective for symptom relief and mucosal healing in most cases. For NSAID-associated peptic ulcer, standard PPI therapy provides healing rates above 90% for duodenal ulcer in 4 weeks and gastric ulcer in 8 weeks. Long-term PPI therapy should be deprescribed if no ongoing indication exists, given associations with Clostridioides difficile infection, hypomagnesemia, bone fracture, and potential small absolute increase in gastric cancer risk in patients with preexisting atrophic gastritis.

Autoimmune Gastritis

Autoimmune gastritis results from immune-mediated destruction of parietal cells, leading to achlorhydria, loss of intrinsic factor, and vitamin B12 deficiency (pernicious anemia). There is no disease-modifying therapy currently available.

• Vitamin B12 replacement (parenteral or high-dose oral) is the cornerstone of treatment for pernicious anemia.
• Iron deficiency anemia should be treated with oral or parenteral iron supplementation.
• PPI therapy in autoimmune gastritis should generally be avoided unless there is a separate specific indication, as these patients already have markedly reduced acid secretion and long-term PPI use may promote hypergastrinemia and increase the risk of type I gastric carcinoid tumors.
• Regular endoscopic surveillance with biopsies is recommended given the increased risk of gastric cancer and gastric neuroendocrine tumors.

H. pylori Treatment Options in Developing Countries

H. pylori treatment options in developing countries must account for regional antibiotic resistance profiles, cost constraints, and drug availability. Metronidazole resistance is particularly high in developing countries—reported at approximately 91% in Africa, 51% in Asia, and 23% in the Americas—and clarithromycin resistance rates also frequently exceed 15% in many regions, negating the utility of standard PPI-clarithromycin triple therapy as an empiric choice.

First-Line Therapies
PPI + amoxicillin + clarithromycin (All twice daily for 14 days; only if clarithromycin resistance rate <15% in the region or susceptibility confirmed)	Used when clarithromycin susceptibility is likely or confirmed Eradication rates have fallen to 70–85% in many regions due to rising clarithromycin resistance; 14 days preferred over 7-day courses Other inexpensive macrolides (e.g. azithromycin) are available over the counter in some developing countries, but macrolide cross-resistance affects eradication rates and their use is not recommended
If clarithromycin resistance rate is >15%: Bismuth quadruple therapy: PPI b.i.d. + bismuth + tetracycline + metronidazole (all q.i.d.) for 14 days (optimized BQT)	Preferred empiric first-line in high-resistance settings per both ACG 2024 and Maastricht VI 2022 May be cheaper than some triple therapy alternatives More complex to take (up to 14–16 pills per day); prepackaged single capsule formulations (e.g., Pylera®) improve compliance where available In vitro metronidazole resistance may be overcome by using higher doses (500 mg t.i.d.–q.i.d.) and 14-day duration
If bismuth is not available: Concomitant therapy: PPI + clarithromycin + metronidazole + amoxicillin for 14 days (acceptable when clarithromycin resistance is <15% and metronidazole resistance is <40%)
Furazolidone-containing regimens (where available and bismuth or clarithromycin resistance is a concern): PPI + furazolidone + amoxicillin (triple therapy) for 14 days PPI + furazolidone + bismuth + tetracycline or amoxicillin (quadruple therapy) for 14 days Furazolidone can replace metronidazole in bismuth quadruple therapy where metronidazole resistance is high
Second-Line Therapies (after failure of clarithromycin-containing regimens)
PPI + bismuth + tetracycline + metronidazole for 14 days (optimized BQT; preferred per Maastricht VI and ACG 2024) PPI + amoxicillin + levofloxacin for 14 days (only if levofloxacin susceptibility confirmed by AST) PPI + furazolidone + tetracycline + bismuth for 14 days PPI + furazolidone + levofloxacin for 10–14 days (where levofloxacin susceptible)
Third-Line Therapies (after failure of clarithromycin-containing regimens and quadruple therapy)
Antibiotic susceptibility testing strongly recommended to guide all third-line regimen selection PPI + amoxicillin + levofloxacin for 14 days (only if levofloxacin susceptible) PPI + amoxicillin + rifabutin for 14 days (use cautiously in TB-endemic areas) PPI + furazolidone + levofloxacin for 10–14 days (where available and levofloxacin susceptible)

• b.i.d. (twice a day); q.i.d. (four times a day); PPI = proton pump inhibitor; BQT = bismuth quadruple therapy; AST = antibiotic susceptibility testing

Furazolidone in Developing Countries

Furazolidone is a nitrofuran antibiotic that has been used to eradicate H. pylori in developing countries for decades due to its low resistance rate and low cost, and has demonstrated effectiveness in both first- and second-line eradication settings. In a retrospective study from Iran, a furazolidone-based quadruple regimen (PPI + bismuth + amoxicillin + furazolidone for 14 days) achieved H. pylori eradication in 90% of patients who had previously failed a metronidazole-based quadruple regimen—a setting where high rates of metronidazole resistance are encountered. In populations with high metronidazole resistance, furazolidone-containing quadruple regimens (PPI + amoxicillin + bismuth subcitrate + furazolidone for 2 weeks) achieve comparable eradication rates to clarithromycin-based quadruple therapy and are an attractive and cost-effective alternative.

Furazolidone is not available in the United States or United Kingdom due to regulatory restrictions. Adverse effects include nausea, vomiting, headache, and malaise; rare but serious risks include hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency, and MAO inhibitor-type interactions (patients must restrict dietary tyramine during treatment). Prolonged high-dose use carries additional risks and should be avoided.

Testing to Prove Eradication After Antibiotic Therapy

Confirmation of H. pylori eradication after treatment is mandatory for all patients per the 2024 ACG Clinical Guideline. Resolution of symptoms is an unreliable indicator of successful eradication and must not substitute for objective testing. The following are the indications for and requirements of testing to prove eradication after antibiotic therapy:

Indications for test of cure (all patients should be tested):

• All patients who have received H. pylori eradication therapy
• Any patient with an H. pylori-associated peptic ulcer
• Individuals with persistent dyspeptic symptoms despite the test-and-treat strategy
• Those with H. pylori-associated MALT lymphoma
• Individuals who have undergone resection of early gastric cancer

Timing and Requirements for Post-Treatment Testing

Requirement	Details
Minimum interval after completing antibiotics	At least 4 weeks after completion of all antibiotic therapy. Testing before 4 weeks yields false-negative results due to temporary bacterial suppression rather than true eradication.
PPI / PCAB hold before testing	PPIs and PCABs (e.g., vonoprazan) must be discontinued for at least 2 weeks prior to testing to minimize false-negative results. Patients may be bridged with H2-receptor antagonists and antacids during this period.
Serology	Must NOT be used for post-treatment test of cure. Antibody titers decline slowly and cannot reliably distinguish active from resolved infection.

Preferred Confirmatory Tests

Test	Sensitivity	Specificity	Notes
Urea breath test (¹³C-UBT)	94.7–97%	95–100%	Preferred non-invasive test; gold standard for post-treatment confirmation. Requires PPI hold ≥2 weeks.
Fecal antigen test (FAT) — validated monoclonal laboratory assay	>90%	>95%	Acceptable alternative to UBT; must use a validated laboratory-based monoclonal assay (not older polyclonal assays). Requires PPI hold ≥2 weeks.
Upper endoscopy with biopsy (rapid urease test, culture, histology, or PCR)	Variable by method	Variable	Reserved for patients requiring endoscopy for other clinical indications (e.g., alarm features, gastric ulcer healing confirmation, MALT lymphoma surveillance). Allows concurrent antibiotic susceptibility testing.

A positive test of cure constitutes treatment failure and mandates use of a completely different antibiotic regimen, ensuring previously used antibiotics are not repeated. After two documented treatment failures, antibiotic susceptibility testing is strongly recommended to guide all subsequent regimen selection.