What is the recommended diagnostic test and first‑line treatment regimen for Helicobacter pylori infection in an adult without known drug allergies?

H. pylori Diagnosis and Treatment

For adults without drug allergies, use the urea breath test (UBT) or laboratory-based monoclonal stool antigen test as first-line diagnostic methods, and treat with 14-day bismuth quadruple therapy or 14-day concomitant therapy as first-line regimens. 1, 2

Diagnostic Testing Strategy

Non-Invasive Testing (Preferred Initial Approach)

The urea breath test is the most accurate non-invasive diagnostic method, with sensitivity of 94-97% and specificity of 95-97.7%. 1, 2, 3 This test detects active infection by measuring urease activity and outperforms all other non-invasive options. 3

Laboratory-based monoclonal stool antigen tests are equally acceptable, with sensitivity and specificity of approximately 93%. 1, 2, 3 However, you must specifically request the monoclonal antibody version—rapid in-office immunochromatographic stool tests have markedly lower accuracy (80-81%) and should be avoided. 2

Critical Medication Washout Requirements

Stop proton pump inhibitors for at least 2 weeks before testing with UBT, stool antigen, rapid urease test, histology, or culture. 1, 2, 3 PPIs suppress bacterial load and cause 10-40% false-negative rates across these methods. 2 If acid suppression is needed during the washout period, substitute an H2-receptor antagonist, which does not affect bacterial load. 1, 2

Discontinue antibiotics and bismuth compounds for at least 4 weeks before testing. 2, 3 These agents temporarily reduce bacterial density and produce false-negative results. 1

When to Use Serology (Limited Role)

Serology should generally not be used because it cannot distinguish active infection from past exposure, with overall accuracy of only 78% (range 68-82%). 1, 2 Antibodies persist long after eradication, creating a "serologic scar" that leads to false-positive results. 1

Consider validated IgG serology only when patients cannot stop PPIs or antibiotics and testing cannot be delayed, or in contexts of gastric atrophy, malignancy, or ulcer bleeding where bacterial load is low. 2 Serology is the only test unaffected by these factors. 1, 2

Never use serology to confirm eradication after treatment. 1, 2, 3

When to Proceed Directly to Endoscopy

Perform endoscopy with invasive testing (rapid urease test, histology, or culture) in these situations: 2, 3

• Age ≥50 years with new-onset dyspepsia 2, 3
• Any alarm symptoms regardless of age: bleeding, unintentional weight loss, dysphagia, palpable abdominal mass, anemia, or malabsorption 2, 3
• Family history of gastric cancer 2
• Failed eradication therapy requiring culture and antimicrobial susceptibility testing 2, 3

Histology requires at least two biopsy samples from both antrum and body to avoid missing patchy colonization. 2, 3 Single antral biopsies detect infection in only 90% of cases. 2

First-Line Treatment Regimens

Bismuth Quadruple Therapy (14 Days)

Bismuth quadruple therapy for 14 days is a first-line empiric option when local clarithromycin resistance is ≥15%. 2, 4 This regimen consists of:

• Bismuth subsalicylate or bismuth subcitrate
• Tetracycline
• Metronidazole
• Proton pump inhibitor (PPI)

All components are taken four times daily with meals. 2

Concomitant Therapy (14 Days)

Fourteen-day concomitant therapy is equally recommended as first-line treatment in areas of high clarithromycin resistance (≥15%). 4 This regimen includes:

• PPI
• Clarithromycin
• Amoxicillin
• Metronidazole

All four agents are given simultaneously. 4

PPI Selection and Dosing

Use esomeprazole 20-40 mg twice daily or rabeprazole 20-40 mg twice daily for optimal acid suppression. 2 Avoid pantoprazole, which provides inferior outcomes. 2

Alternative First-Line Option

In areas of low clarithromycin resistance (<15%), 14-day triple therapy (PPI + clarithromycin + amoxicillin) is acceptable. 4 However, given rising resistance rates globally, bismuth quadruple therapy or concomitant therapy are safer empiric choices. 4

Confirmation of Eradication

Test for eradication at least 4 weeks after completing treatment using UBT or monoclonal stool antigen test—never serology. 2, 3 This timing avoids false-negative results from temporary bacterial suppression. 5

Ensure the patient has been off PPIs for ≥2 weeks and off antibiotics/bismuth for ≥4 weeks before confirmation testing. 2, 3

Common Pitfalls to Avoid

• Do not order H. pylori testing while the patient is taking PPIs unless you deliberately choose serology for specific clinical circumstances. 2
• Do not use rapid in-office stool antigen kits; always specify laboratory-based monoclonal assays. 2
• Do not use IgG/IgA/IgM antibody panels; they provide no added value over validated IgG testing and often include non-FDA-approved tests of unclear diagnostic value. 1, 2
• Do not rely on single antral biopsies during endoscopy; obtain at least two samples from both antrum and body. 2, 3
• Do not use serology for post-treatment confirmation; antibodies remain elevated after eradication. 1, 2, 3

Second-Line and Rescue Therapy

After first-line treatment failure, use 14-day levofloxacin triple therapy (PPI + levofloxacin + amoxicillin) or 14-day bismuth quadruple therapy if not previously used. 4

For patients with multiple treatment failures, perform endoscopy with culture and antimicrobial susceptibility testing to guide therapy. 3, 4 If culture is unavailable, use antibiotics not previously administered or for which resistance is unlikely (amoxicillin, tetracycline, bismuth, or furazolidone). 4