H Pylori Bacteria Infection, Symptoms, Causes, Diagnosis, Treatment
H Pylori Bacteria Infection (Helicobacter pylori), previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. However, over 80 percent of individuals infected with the bacterium are asymptomatic and it has been postulated that it may play an important role in the natural stomach ecology.
More than 50% of the world’s population harbor H. pylori in their upper gastrointestinal tract. Infection is more prevalent in developing countries, and incidence is decreasing in Western countries. H. pylori’s helix shape (from which the generic name is derived) is thought to have evolved to penetrate the mucoid lining of the stomach.
H Pylori Bacteria Infection
Signs and Symptoms:
Over 80% of people infected with H. pylori show no symptoms. Acute infection may appear as an acute gastritis with abdominal pain (stomach ache) or nausea. Where this develops into chronic gastritis, the symptoms, if present, are often those of non-ulcer dyspepsia: stomach pains, nausea, bloating, belching, and sometimes vomiting or black stool.
Individuals infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers and a 1 to 2% risk of acquiring stomach cancer. Inflammation of the pyloric antrum is more likely to lead to duodenal ulcers, while inflammation of the corpus (body of the stomach) is more likely to lead to gastric ulcers and gastric carcinoma. However, it is possible that H. pylori plays a role only in the first stage that leads to common chronic inflammation, but not in further stages leading to carcinogenesis.
H Pylori Bacteria Infection
Microbiology:
H. pylori is a helix-shaped (classified as a curved rod, not spirochaete) Gram-negative bacterium. It is microaerophilic; that is, it requires oxygen, but at lower concentration than is found in the atmosphere.
It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) produced by intestinal bacteria. It produces oxidase, catalase, and urease.
It is capable of forming biofilms and can convert from spiral to a possibly viable but nonculturable coccoid form, both likely to favor its survival and be factors in the epidemiology of the bacterium.
H Pylori Bacteria Infection
Pathophysiology:
To colonize the stomach, H. pylori must survive the acidic pH of the lumen and use its flagella to burrow into the mucus to reach its niche, close to the stomach’s epithelial cell layer. Many bacteria can be found deep in the mucus, which is continuously secreted by mucus-secreting cells and removed on the luminal side.
To avoid being carried into the lumen, H. pylori senses the pH gradient within the mucus layer by chemotaxis and swims away from the acidic contents of the lumen towards the more neutral pH environment of the epithelial cell surface.
H. pylori is also found on the inner surface of the stomach epithelial cells and occasionally inside epithelial cells. H. pylori produces large amounts of the enzyme urease, molecules of which are localized inside and outside of the bacterium. Urease breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia.
The ammonia is converted to ammonium by accepting a proton (H+), which neutralizes gastric acid. The survival of H. pylori in the acidic stomach is dependent on urease. The ammonia produced is toxic to the epithelial cells, and, along with the other products of H. pylori—including proteases, vacuolating cytotoxin A (VacA), and certain phospholipases,— damages those cells.
Colonization of the stomach by H. pylori results in chronic gastritis, an inflammation of the stomach lining. The severity of the inflammation is likely to underlie H. pylori-related diseases. Duodenal and stomach ulcers result when the consequences of inflammation allow the acid and pepsin in the stomach lumen to overwhelm the mechanisms that protect the stomach and duodenal mucosa from these caustic substances.
The type of ulcer that develops depends on the location of chronic gastritis, which occurs at the site of H. pylori colonization.
Diagnosis:
Colonization with H. pylori is not a disease in and of itself but a condition associated with a number of disorders of the upper gastrointestinal tract. Testing for H. pylori is recommended if there is peptic ulcer disease, low grade gastric MALT lymphoma, after endoscopic resection of early gastric cancer, if there are first degree relatives with gastric cancer, and in certain cases of dyspepsia, not routinely.
Several ways of testing exist. One can test noninvasively for H. pylori infection with a blood antibody test, stool antigen test, or with the carbon urea breath test.
However, the most reliable method for detecting H. pylori infection is a biopsy check during endoscopy with a rapid urease test, histological examination, and microbial culture.
There is also a urine ELISA test with a 96% sensitivity and 79% specificity.
None of the test methods is completely failsafe. Even biopsy is dependent on the location of the biopsy. Blood antibody tests, for example, range from 76% to 84% sensitivity. Some drugs can affect H. pylori urease activity and give false negatives with the urea-based tests.
H Pylori Bacteria Infection
Treatment:
Approach to selecting an antibiotic regimen
Initial antibiotic regimens for H. pylori can be broadly divided into bismuth, clarithromycin, and levofloxacin containing regimens.
The choice of initial antibiotic regimen to treat H. pylori should be guided by the presence of risk factors for macrolide resistance and the presence of a penicillin allergy. In patients with one or more risk factors for macrolide resistance, clarithromycin-based therapy should be avoided.
Clarithromycin-based therapy:
- Triple therapy — Clarithromycin triple therapy consists of clarithromycin, amoxicillin, and a PPI, all given twice daily for 14 days, as longer duration of treatment may be more effective in curing infection.
- Metronidazole can be substituted for amoxicillin in penicillin-allergic individuals. PPI-clarithromycin-metronidazole and PPI-clarithromycin-amoxicillin regimens are equivalent.
- Concomitant therapy — Concomitant therapy consists of a clarithromycin, amoxicillin, a nitroimidazole (tinidazole or metronidazole), and a PPI administered together.
- If concomitant therapy is used to treat H. pylori, the regimen should be continued for 10 to 14 days.
- Hybrid therapy — Hybrid therapy consists of amoxicillin and a PPI for seven days followed by amoxicillin, clarithromycin, a nitroimidazole, and a PPI for seven days.
- Hybrid therapy has been suggested as an alternative to clarithromycin triple therapy.
- The complexity of the treatment regimen has limited its use as a first-line regimen in the treatment of H. pylori.
- Sequential therapy — The 10-day clarithromycin-containing sequential therapy regimen consists of amoxicillin and a PPI for five days, followed by clarithromycin and nitroimidazole (eg, metronidazole) plus a PPI for five days.
- Given the complexity of the sequential therapy regimen and the lack of superiority to 14 day clarithromycin triple therapy in North America, clarithromycin-containing sequential therapy has not been uniformly endorsed by guidelines as a first-line therapy.
Bismuth quadruple therapy:
- Bismuth quadruple therapy consists of bismuth subsalicylate, metronidazole, tetracycline, and a PPI given for 14 days.
- A combination capsule (Pylera) containing bismuth subcitrate, metronidazole, and tetracycline has been approved by the United States FDA.
- A regimen using the combination capsule (3 capsules 4 times daily plus PPI twice daily) is somewhat simpler than standard quadruple therapy (4 to 8 pills 4 times daily and a PPI twice daily).
- If tetracycline is not available, doxycycline may be substituted.
Levofloxacin based therapy:
Studies evaluating the efficacy of levofloxacin containing regimens in North America are lacking. Limited data suggest that fluoroquinolone resistance rates in North America are high. Levofloxacin resistance decreases the eradication success rate of levofloxacin containing regimens by 20 to 40%. However, based on results from international trials, levofloxacin triple therapy may have a role in the treatment of H. pylori as a salvage regimen.
- Levofloxacin triple therapy – Levofloxacin triple therapy consists of levofloxacin, amoxicillin, and a PPI for 10 to 14 days.
- Metronidazole can be substituted for amoxicillin in penicillin-allergic individuals.
- Levofloxacin quadruple therapy – Limited data support the use of quadruple therapy with levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD). In an open label prospective trial, H. pylori treatment-naïve patients randomized to LOAD for 7 or 10 days had significantly higher eradication rates as compared with clarithromycin triple therapy for 10 days (89, 90, and 73%, respectively). However, additional studies are needed to confirm these results and determine whether this more expensive regimen is cost-effective.
- Levofloxacin sequential therapy – Levofloxacin sequential therapy consists of amoxicillin and a PPI for five to seven days followed by levofloxacin, amoxicillin, a nitroimidazole and a PPI for five to seven days.
H Pylori Bacteria Infection
H. Pylori Bacteria Infection Treatment Mnemonic:
H. pylori treatment mnemonic
H Pylori Bacteria Infection
Confirmation of Eradication:
Tests to confirm eradication should be performed in all patients treated for H. pylori. Eradication may be confirmed by a urea breath test, fecal antigen test, or upper endoscopy performed four weeks or more after completion of antibiotic therapy.
PPI therapy should be withheld for one to two weeks prior to testing.
Endoscopy with biopsy for culture and sensitivity should be performed in patients with persistent H. pylori infection after two courses of antibiotic treatment.
H Pylori Bacteria Infection
Treatment Failure:
Approximately 20% of patients fail an initial attempt at H. pylori eradication. Such patients require salvage therapy.
In patients with persistent H. pylori infection, the choice of antibiotic therapy should be guided by the patient’s initial treatment regimen and the presence of relevant antibiotic allergies.
For patients failing a course of H. pylori treatment, an alternate regimen using a different combination of medications.
In general, clarithromycin and antibiotics used previously should be avoided if possible.
H Pylori Bacteria Infection