Drugs In Practice

Table 3 – Preferred regimens for Helicobacter pylori infection1

Drug Usual Adult Dosage2 Comments

Empiric Treatment

Bismuth Quadruple Therapy3

Bismuth subsalicylate4 + metronidazole + tetracycline5 + a PPI

Rifabutin Triple Therapy7

Rifabutin + amoxicillin + esomeprazole or rabeprazole

Susceptibility-Based Treatment

Clarithromycin Triple Therapy

Clarithromycin8 + amoxicillin + a PPI

Levofloxacin Triple Therapy

Levofloxacin + amoxicillin + a PPI

Metronidazole Triple Therapy

Metronidazole + amoxicillin + a PPI

PPI = proton pump inhibitor

262 or 525 mg PO qid

500 mg PO qid

500 mg PO bid or qid

See footnote6

150 mg bid

1 g tid 40 mg bid

• Preferred first-line option

• Alternative first-line option

• Can be used in treatment-naive patients or for salvage treatment

500 mg PO bid

1 g PO bid

See footnote6

500 mg PO once/day

1 g PO bid

See footnote6

500 mg PO once/day

1 g PO bid

See footnote6

1. Adapted from Y-C Lee et al. Annu Rev Med 2022; 73:183.

2. The optimal duration of treatment is 14 days.

• Should only be used in patients who reside in areas where clarithromycin resistance is <15% and in patients with no prior macrolide exposure for any indication9

• Levofloxacin resistance is a concern

• Metronidazole resistance is a concern

3. The fixed-dose combination of bismuth subcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg can be used, but it is only packaged as a 10-day supply; dosage is 3 capsules qid.

4. Or bismuth subcitrate 120-300 mg.

5. Generic tetracycline may not be available.

6. Esomeprazole 20 mg bid, lansoprazole 45 mg bid, omeprazole 40 mg bid, pantoprazole 40 mg bid, or rabeprazole 20 mg bid.

7. A fixed-dose combination of rifabutin 12.5 mg, omeprazole 10 mg, and amoxicillin 250 mg is available.

8. Clarithromycin may increase the risk of cardiac adverse effects and death in patients with coronary artery disease (FDA Drug Safety Communication, February 2018).

9. Clarithromycin resistance rates are considered to be ≥15% unless local resistance patterns that show otherwise are available.

Urea Breath Tests

A urea breath test can be used for clinic-based diagnosis of active infection and confirmation of eradication. These tests typically have >90% sensitivity and specificity, and results are available within 10-20 minutes, but they require use of a mass spectrophotometer.

Stool Antigen Tests

Stool antigen enzyme immunoassay (EIA) testing also has >90% sensitivity and specificity and can test for active infection and eradication. It does not require special equipment and may be less expensive than urea breath tests. Stool samples can be used for molecular testing to determine antimicrobial susceptibility.

Serology

Serologic antibody tests for H. pylori lack sensitivity and specificity and do not differentiate between active and past infection. They cannot be used to confirm H. pylori eradication.

Endoscopy with Biopsy

H. pylori can be diagnosed from endoscopic biopsies using urease testing, histopathology, or culture. Urease testing of biopsy specimens has >90% sensitivity and specificity. Rapid tests are available that provide results in one hour. Histologic diagnosis from biopsy specimens has >95% sensitivity and specificity, but it takes longer and is more expensive than urease testing. Culture permits testing for antimicrobial susceptibility.

Drug Interference

The sensitivity of urea breath tests, stool antigen tests, and urease testing of biopsy specimens for H. pylori is reduced by use of PPIs, bismuth-containing products, and antibiotics. Patients should not take a PPI for at least 1-2 weeks or a bismuth-containing product or antibiotics for at least 4 weeks before these tests.

ERADICATION OF H. pylori

Preferred regimens for eradication of H. pylori infection are listed in Table 3.

In clinical trials, combinations of antibacterial drugs have been successful in eradicating H. pylori , but in clinical practice, eradication rates have been lower because of bacterial resistance and poor patient adherence to multidrug regimens. Local resistance patterns and antimicrobial susceptibility testing should guide the selection of antibacterial drugs, but they are not readily available.

Bismuth quadruple therapy (bismuth, metronidazole, tetracycline, and a PPI) is recommended for first-line treatment of H. pylori infection. 26 H. pylori resistance to tetracycline is rare, and adequate dosing of metronidazole can be effective even in the presence of in vitro resistance. 27

Rifabutin triple therapy (rifabutin, amoxicillin, and a PPI) is an alternative option for empiric treatment of H. pylori infection. A fixed-dose combination of omeprazole, amoxicillin, and rifabutin eradicated H. pylori in about 80% of treatmentnaive patients in two small clinical trials and is FDA-approved for treatment of H. pylori infection in adults.28 Rifabutin-based triple therapy has not been compared directly to other regimens for firstline treatment of H. pylori infection in adults. Rates of H. pylori resistance to rifabutin have been low; whether more widespread use as part of a first-line regimen would increase resistance rates remains to be determined.

The efficacy of clarithromycin against H. pylori has been diminished by increasing antimicrobial resistance. Regimens containing clarithromycin should be used for first-line treatment only when antimicrobial susceptibility tests have shown that H. pylori is susceptible to the drug or in patients who have no history of macrolide use for any indication and reside in areas where H. pylori resistance to clarithromycin is known to be <15%. Limited data are available on H. pylori resistance rates; they should be assumed to be ≥15% unless local resistance patterns show otherwise.

Adequate acid suppression with a PPI is associated with higher H. pylori cure rates. A higher intragastric pH improves antibiotic stability and bioavailability, resulting in higher drug concentrations. It also promotes H. pylori replication, making it more susceptible to antibiotic treatment. The potency of PPIs in maintaining a higher