What is the recommended diagnostic workup and first‑line treatment for a patient with suspected Helicobacter pylori infection?

Diagnostic Workup and First-Line Treatment for Suspected H. pylori Infection

Diagnostic Strategy Based on Age and Alarm Symptoms

For patients under 50 years without alarm symptoms, use non-invasive testing with either the 13C-urea breath test (UBT) or laboratory-based monoclonal stool antigen test as first-line diagnostics. 1, 2

Age-Stratified Approach

• Patients under 40-50 years with uncomplicated dyspepsia should undergo non-invasive H. pylori testing (UBT or stool antigen test) without endoscopy. This "test and treat" strategy reduces unnecessary endoscopies by 62% while maintaining equivalent safety and symptom resolution. 1, 3

• Patients over 50 years with new-onset dyspepsia require direct endoscopy with invasive testing due to markedly increased gastric cancer risk (approximately 19 cases/100,000 men and 9 cases/100,000 women in the European Community). 1

• Any patient with alarm symptoms—regardless of age—requires immediate endoscopy: bleeding, unintentional weight loss, dysphagia, palpable abdominal mass, anemia, or malabsorption. 1, 3

Critical Pre-Test Medication Management

Stop proton pump inhibitors (PPIs) for at least 2 weeks before performing UBT, stool antigen test, rapid urease test, histology, or culture. PPIs cause 10-40% false-negative results by suppressing bacterial load. 1, 2

• Discontinue antibiotics and bismuth for at least 4 weeks before testing. 1, 2

• Serology is the only test unaffected by ongoing PPI therapy and may be used when patients cannot stop PPIs, though it cannot distinguish active infection from past exposure and has only 78% overall accuracy. 1

Recommended Diagnostic Tests

Non-Invasive Tests (Preferred for Initial Diagnosis)

• The UBT is the gold standard non-invasive test with sensitivity of 94.7-97% and specificity of 95-100%. 1, 2

• Laboratory-based monoclonal stool antigen test has equivalent accuracy to UBT with sensitivity and specificity of approximately 93%. Both detect active infection rather than past exposure. 1, 2

• Avoid rapid in-office serological tests—they have suboptimal accuracy (sensitivity 63-97%, specificity 68-92%) and should not be used as first-line diagnostics. 1

Invasive Tests (During Endoscopy)

• Rapid urease test provides quick results during endoscopy but has only 80-95% sensitivity in pretreatment patients. 1

• Histology with modified Giemsa staining achieves 90-95% sensitivity when at least two biopsy samples are obtained from both antrum and body. Single biopsies miss infections due to patchy colonization. 1

• Culture with antimicrobial susceptibility testing is advised in areas with high clarithromycin resistance (>15-20%) or after treatment failure. 1, 4

• Molecular testing using next-generation sequencing can detect resistance to clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline, and rifabutin from stool or gastric biopsies. 5

First-Line Treatment Regimens

The only therapies that can be given empirically in most areas are bismuth quadruple therapy for 14 days or rifabutin triple therapy for 14 days. 5, 1

Bismuth Quadruple Therapy (14 Days)

• Bismuth + tetracycline + metronidazole + PPI (twice daily) for 14 days is recommended as first-line empiric treatment when local resistance patterns support >90% cure rate. 1, 6

• Use high-dose potent PPIs (esomeprazole or rabeprazole 20-40 mg twice daily)—avoid pantoprazole. 1, 4

Rifabutin Triple Therapy (14 Days)

• Rifabutin + amoxicillin + PPI for 14 days is an alternative first-line empiric option. 1

Concomitant Non-Bismuth Quadruple Therapy (14 Days)

• PPI + amoxicillin + metronidazole + clarithromycin (PAMC) for 14 days is recommended in areas with low clarithromycin resistance (<15%). 6, 4

Traditional Triple Therapy (Restricted Use)

• PPI + clarithromycin + amoxicillin for 14 days is restricted to areas with known low clarithromycin resistance (<15%) or confirmed susceptibility. Clarithromycin, metronidazole, or fluoroquinolone triple therapies can no longer be used empirically due to increasing resistance. 5, 6

Susceptibility-Based Treatment Selection

All successful antimicrobial therapy is susceptibility-based and optimized to reliably achieve ≥95% cure rates. 5

• Obtain thorough antibiotic use history including review of medical and pharmacy records to exclude antibiotics where preexisting resistance is likely. 5

• Susceptibility testing via culture or molecular methods (next-generation sequencing) should be performed after treatment failure or in high-resistance areas. 5, 4

• Reflex stool testing is especially attractive: if stool antigen test is positive, molecular testing for antimicrobial susceptibility is automatically performed. 5

Confirmation of Eradication

Test of cure is mandatory after treatment of every patient using UBT or stool antigen test performed at least 4 weeks after therapy completion. 5, 1, 2

• Do not use serology to confirm eradication—antibodies remain elevated after H. pylori elimination. 1, 2

• Ensure PPIs are stopped for at least 2 weeks before confirmation testing. 1, 2

Common Pitfalls to Avoid

• Never perform H. pylori testing on patients taking PPIs unless medication has been stopped for ≥2 weeks or serology is used instead. 1

• Do not use rapid in-office serological tests—they have limited accuracy and should be avoided. 1

• Single antral biopsies yield positive results in only 90% of infected stomachs—always obtain biopsies from both antrum and body. 1

• Failure to obtain test of cure provides no feedback regarding treatment effectiveness and allows undetected treatment failures. 5