helicobacter%20pylori%20infection
HELICOBACTER PYLORI INFECTION
Helicobacter pylori is a spiral-shaped gram-negative bacterium involved in the development of gastritis, duodenal and gastric ulcers, and gastric cancer.
Infection is strongly associated with the development of gastric epithelial and lymphoid malignancies.
Acute infection is mostly asymptomatic and is acquired through human-to-human contact via gastro-oral and fecal-oral routes.
Adaptability in gastric conditions and production of urease allow it to colonize the stomach.

Principles of Therapy

  • Eradication of H pylori leads to ulcer healing and significantly diminished incidence of recurrence
    • Elimination of infection reduces gastric cancer incidence; it improves gastritis and gastric atrophy but not intestinal metaplasia
    • Multidrug regimen, adequate duration of treatment, and adherence to therapy are needed for eradication
  • A screen and treat strategy is recommended in individuals and communities at increased risk for gastric cancer

“Test and Treat” for Helicobacter pylori

It is strongly recommended that the following patients should be tested for H pylori and if they test positive for H pylori, treatment to eradicate the infection should be instituted:

  • Before starting NSAID treatment on patients with previous history of PUD or ulcer complication
    • NSAIDs increase the risk of developing complications in patients with concomitant H pylori infection
  • Patients on NSAID and aspirin with a history of PUD 
  • Patients with GERD requiring long-term proton pump inhibitor (PPI) therapy
    • Long-term PPI use of patients infected with H pylori may be associated with acceleration of atrophic gastritis
  • Complicated and uncomplicated peptic ulcers (active or healed)
  • Gastric mucosa-associated lymphoid tissue (MALT) lymphoma
  • Previous history of lymphoma while on NSAID therapy
  • Uninvestigated dyspepsia
  • After resection of early gastric cancer
  • Family history of gastric cancer

Other Patients

Adult patients <50 years (<40 years in areas with high prevalence of gastric cancer) that present with persistent dyspepsia and without predominant GERD symptoms, NSAID therapy and no alarm symptoms may be approached in 2 different ways:

  • Empiric therapy
    • Treat empirically x 2-4 weeks with appropriate antisecretory agent and/or prokinetic agent
    • If symptoms do not improve with appropriate trials of PPI, histamine2-receptor antagonists (H2RAs) or prokinetic agents, consider endoscopy
  • May test for H pylori prior to trial of medication
    • These patients may be considered for “test and treat” but this is controversial in non-ulcer dyspepsia
    • It is unlikely that eradication of H pylori will reduce symptoms but it may decrease future risk of PUD
    • Endoscopy may be performed 1st to identify PUD and treat H pylori only in PUD patients

Pharmacotherapy

  • Regimen for H pylori should be easy to comply with and cost-effective
  • Patients need to be advised that full compliance is important for treatment success
  • Determine any history of prior antibiotic use as this will identify any possible antibiotic resistance 

Recommended Regimens for Initial Therapy

  • Triple therapy using PPI with Clarithromycin and Amoxicillin or Metronidazole is the recommended regimen
    • Many studies have shown that regimens using Ranitidine bismuth citrate (RBC) is as effective as using a PPI; acid suppression with RBC is not as potent as with PPI but it has the advantage of added antimicrobial activity of bismuth
  • Quadruple therapy with Bismuth is an appropriate 1st-line regimen to consider in patients allergic to Penicillin or in areas with high Clarithromycin and Metronidazole resistance
  • Concomitant therapy with a PPI, Clarithromycin, Amoxicillin and a nitroimidazole is also a 1st-line treatment option
  • Sequential therapy, an alternative to Bismuth quadruple therapy, had been shown in multiple randomized trials to be effective for H pylori eradication in treatment-naive patients: PPI + Amoxicillin for 5 days followed by PPI + Clarithromycin + Tinidazole or Metronidazole for another 5 days
  • Hybrid therapy consists of a PPI and Amoxicillin given for 7 days followed by a PPI, Amoxicillin, Clarithromycin and a nitroimidazole for another 7 days 
  • Clarithromycin resistance reduces the efficacy of triple and sequential therapy, Metronidazole resistance reduces the efficacy of sequential therapy, and dual Clarithromycin and Metronidazole resistance reduces the efficacy of sequential, concomitant and hybrid therapy 

Proton Pump Inhibitor (PPI)

  • The PPIs appear to be equally effective when used in the standard dose
  • Prolonging PPI therapy is recommended in gastric ulcer and complicated duodenal ulcer
    • PPI-Clarithromycin-based triple therapy should be up to 14 days, unless shorter therapies had been locally effective
  • The exact mechanism of action in H pylori eradication is unknown; H pylori prefers an acidic medium and it is postulated that the potent acid suppression with PPIs allows the antibiotics to act most effectively on the bacteria

Clarithromycin

  • Binds to ribosomes resulting in protein synthesis inhibition
    • Clarithromycin with Amoxicillin is considered the antibiotic combination of choice for initial therapy

Amoxicillin

  • Inhibits bacterial cell wall synthesis

Metronidazole

  • Causes cell death by inducing breakage of DNA double strands
  • It is thought that avoiding Metronidazole in initial therapy will give better results with the drug when it is used in quadruple therapy after initial treatment failure
  • Metronidazole should be substituted for Amoxicillin in Penicillin-allergic patients
  • If resistance to Metronidazole is a problem (which may be in developing countries), Furazolidone can be used as alternative

Bismuth

  • Cytoprotective effect on gastrointestinal (GI) mucosa
    • Stimulation of prostaglandin production and modulation of immune response
    • Bismuth salt deposits adhere to H pylori cell wall, inducing vacuolization and distortion of bacterial cell and loss of adherence from gastric epithelium
  • If Bismuth is unavailable, consider Levofloxacin, Rifabutin and high dose-dual (PPI with Amoxicillin) therapies

Tetracycline

  • Prevents protein synthesis
  • Doxycycline or Bismuth-containing quadruple therapy combining Amoxicillin-Metronidazole or Furazolidone-Metronidazole may be used if Tetracycline is not available

Treatment Options for Patients with Penicillin Allergy and/or Previous Macrolide Exposure  

  • With penicillin allergy and macrolide exposure: Bismuth quadruple therapy
  • With penicillin allergy but without macrolide exposure: Clarithromycin triple therapy with Metronidazole; Bismuth quadruple therapy   
  • Without penicillin allergy but with macrolide exposure: Bismuth quadruple therapy; Levofloxacin triple or sequential therapy
  • Without penicillin allergy or macrolide exposure: Bismuth quadruple therapy; concomitant therapy; Clarithromycin triple therapy with Amoxicillin

Adjuvant Therapy

Probiotics

  • Live bacteria that help restore microbial balance in the intestine
  • Reduces risk of adverse effects from H pylori treatment, though additional studies still need to be done
Various H pylori-associated PUD combination preparations are available. Please see the latest MIMS for specific formulations and prescribing information.

Alternative Regimens For Initial Treatment Failure

  • Treatment failure occurs when symptoms persist or recur within 14 days after completion of therapy
    • May be due to noncompliance, intake of NSAIDs, antimicrobial resistance, penicillin allergy, or cigarette smoking
  • Selection of treatment options should be guided by local antimicrobial resistance data and patient’s prior antibiotic exposure 
    • When 1st-line therapy is unsuccessful, 2nd-line therapy should avoid antibiotics that had been previously used
  • Quadruple therapy with PPI, Bismuth, Metronidazole and Tetracycline taken for 7-14 days is typically the preferred regimen after initial treatment failure and for high Clarithromycin resistance
    • If Bismuth is not available, concomitant therapy with PPI, Clarithromycin, Amoxicillin, and a nitroimidazole for 14 days may be used
  • Triple therapy with Levofloxacin for 14 days may also be given after initial treatment failure and for high Clarithromycin resistance
  • If the alternative regimens fail, patient should be referred to an expert and antibiotic susceptibility testing should be considered to guide retreatment
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