Helicobacter pylori

H pylori is strongly urease positive. This is important for their survival in the gastric environment. Urease converts urea to ammonia, which helps the bacteria to survive in an acidic environment.

H pylori is distributed worldwide, and it is the commonest chronic bacterial infection. It is estimated that 50% of the world population is infected, higher in black and Hispanic populations and resource-poor countries. The prevalence rate in the UK is 40%.

Salted food has been associated with persistent H pylori infection.

Humans are the reservoir of H pylori.

How is Helicobacter pylori acquired?

Most people get infected during childhood. The route of transmission is not clear but possibly faeco-oral, oro-oral and via contaminated water and food.

• Chronic diffuse superficial gastritis

• Gastric and duodenal ulcer

• Non-ulcer dyspepsia (some cases)

• Gastric adenocarcinoma (not involving gastric cardia)

• Gastric MALT-type B cell lymphoma

• Idiopathic thrombocytopenic purpura

There are 4 major types of tests that we can use to test for H pylori.

Other tests, that could be performed when needed -

• PCR for identification and clarithromycin resistance,

• Histology

There are 2 SMIs related to H pylori- Identification of Helicobacter spp. (SMI ID26) & Investigation of infectious causes of dyspepsia.

Laboratory safety

• Containment level 2.

• Laboratory procedures that give rise to infectious aerosols must be conducted in a microbiological safety cabinet.

Transporting media

• Dent’s transport medium.

• Alternatively, isotonic saline can be used.

Process the specimen within 6 hours; if not, store at 4 degrees C covered with 1mL brain-heart infusion broth for 48 hrs.

Stain

• The organism may be stained using Giemsa or gram stain. Use carbol fuchsin or Sandiford’s counterstain.

• Stain smears from blood cultures with acridine orange rather than Gram stain.

• Gram-negative, long, thin, straight or slightly curved to spiral-shaped rods. It could be spiral/helical and even coccoid (in older cultures).

Plate selection

• H pylori selective media or Dent selective media: blood agar with dent supplement (vancomycin, trimethoprim, cefsoludin and amphotericin B). Incubation is microaerophilic, with 3-5% H2 @35 degrees C for 10 days.

• Chocolate/blood agar

• If the urease test has not been performed (i.e. UBT, see above), use Christenson’s Urea broth.

Colony

• Small (1mm), grey, translucent and maybe slightly haemolytic after 3-5 days. Longer incubation may show swarming colonies.

Identification

• Catalase, and oxidase-positive; Urease reaction is variable for different species, but H pylori is strongly positive.

• PCR & MALI ToF

Sensitivity test

• Use MIC. Report – Amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline.

• Rifampicin is the 2nd line.

• EUCAST breakpoints are available.

Other tests that can be done on biopsy

• PCR for identification and clarithromycin resistance, histology and urease test.

Whom to test?

• Patients with uncomplicated dyspepsia unresponsive to lifestyle change and antacids,

• following a single one month course of proton pump inhibitor (PPI),

• without alarm symptoms.

• (A trial of PPI should usually be prescribed before testing unless the likelihood of H pylori is higher than 20%, for example, older people, people of North African ethnicity and those living in a known high-risk area, in which case the patient should have a test for H pylori first, or in parallel with a course of PPI.)

• Patients with a history of gastric or duodenal ulcer/bleed who have not previously been tested.

• Patients before taking NSAIDs, if they have a prior history of gastro-duodenal ulcers/bleeds.

• Patients with unexplained iron-deficiency anaemia, after negative endoscopic investigation, have excluded gastric and colonic malignancy, and investigations have been carried out for other causes, including cancer; idiopathic thrombocytopenic purpura; vitamin B12 deficiency.

When not to test

• Patients with proven oesophagitis, or predominant symptoms of reflux, suggesting gastro-oesophageal reflux disease (GORD).

• Children with functional dyspepsia.

https://www.gov.uk/government/publications/helicobacter-pylori-diagnosis-and-treatment

Which test to perform?

• Urea Breath Test (UBT) – most accurate test.

• Stool Helicobacter Antigen Test (SAT) or

• Validated serology (only IgG) – not recommended in most patients. Positive results must be confirmed with a 2nd test UBT/SAT/biopsy. However, it has an excellent negative predictive value.
  Serology is also useful in cases of GI bleed. Blood and PPI can interfere with the UBT and SAT. Serology can be used to confirm negative UBT/SAT.

Precaution before the test

• Leave a 2-week washout period after proton pump inhibitor (PPI) before a UBT/SAT.

• Ensure that no antibiotics have been taken for any infection in the 4 weeks before UBT/SAT.

H pylori resistance rate in the UK

• Metronidazole: 22-88%

• Clarithromycin: 3-68%

• Levofloxacin: 17%

• Amoxicillin, rifampicin, tetracycline: 3%

• Rifabutin: <1%

• Do not routinely offer retesting after eradication.

Indications for retest

• If compliance is poor, or has high local resistance rates.

• Persistent symptoms, and HP test performed within two weeks of taking PPI, or within four weeks of taking antibiotics.

• Patients with an associated peptic ulcer or MALT lymphoma, or after resection of early gastric carcinoma.

• Patients requiring aspirin, where PPI is not co-prescribed.

• Patients with severe persistent or recurrent symptoms, particularly if not typical of GORD.

• Family history of gastric malignancy.

• NSAID/Aspirin is indicated and a history of peptic ulcer.

• Anxiety.

[NICE CKS, PHE quick reference guide]

When to retest?

• Wait at least four weeks (ideally eight weeks) after treatment. If acid suppression is needed, use an H2 antagonist.

• As per NICE: Offer people with peptic ulcers (gastric or duodenal) and H pylori retesting for H pylori 6 to 8 weeks after beginning treatment, depending on the size of the lesion.

Which test to use?

• Urea breath test – most accurate.

• Stool antigen test – alternative.

Serology or near-patient test – not indicated/recommended.

What if the repeat test is positive?

• Use second-line treatment if UBT or SAT remains positive.

• Also – Reassess for underlying pathology/alternative diagnosis, check for compliance, check for adherence to lifestyle changes & check if the initial test was performed within 2 weeks of PPI or 4 weeks of antibiotic.

Stop quinolone treatment at first signs of a serious adverse reaction (such as tendonitis), prescribing with special caution in people over 60 years and avoiding co-administration with a corticosteroid.

Seek advice from a gastroenterologist if eradication of H pylori is not successful with second-line treatment.

3rd line regimen on specialist advice: 10 days of PPI twice daily, PLUS bismuth subsalicylate 525mg QDS, PLUS 2 antibiotics as above not previously used, OR rifabutin 150mg BD, OR furazolidone 200mg BD.

• Treatment with a second-line H. pylori eradication regimen has been unsuccessful.

• There are limited antibiotic options for H. pylori eradication therapy, due to hypersensitivity, known local high antibiotic resistance rates, or previous use of clarithromycin, metronidazole, and a quinolone.

• Gastric biopsy should be considered
  1. after 1st treatment failure, if endoscopy is being done.
  2. on all cases, if there is a 2nd treatment failure.

• Culture and sensitivity can direct treatment in refractory cases.

• SMI ID 26: identification of Helicobacter species

• UK SMI B 55: investigation of infectious causes of dyspepsia

• UKHSA –Helicobacter pylori in dyspepsia: test and treat

• NICE –Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management

• NICE CKS – Dyspepsia – unidentified cause

• NICE Pathways- Helicobacter pylori testing and eradication in adults