Update on the Diagnosis and Management of Helicobacter Pylori Infection

Helicobacter pylori infection remains the single most common cause of peptic ulcer disease and is also frequently documented in patients with dyspepsia in the absence of peptic ulcer disease.

The most recent and relevant management guidelines are those of American College of Gastroenterology (AVG)1 and the Maastricht IV/Florence consensus report these were published in 2007 and 2012, respectively.

Currently recommended treatment regimens are not performing as well as when they were initially introduced, due largely to increasing problems with antimicrobial resistance

DIAGNOSIS OF HELICOBACTER PYLORI INFECTION

The diagnosis of H. Pylori infection can be made either endoscopically or nonendoscopically. Determining the optimal choice of diagnostic test depends on a variety of factors including clinical situation, prevalence of infection, and recent use of proton pump inhibitors (PPIs), bismuth, or antibiotics.

Nonendoscopic (Noninvasive) Methods

Serology:

Serological testing is widely available and generally inexpensive. Serological testing for IgG antibodies to H. Pylori has traditionally been apopular method for the diagnosis of the infection particularly in the primary care setting. In low prevalence areas, serology has reasonable sensitivity for the diagnosis of H. Pylori infection. However, its specificity is low resulting in a high proportion of false positive results. Therefore, a positive Serological test in an individual from a low prevalence area should be confirmed with another method such as a urea breath test (BUT) or stool antigen test.

Urea breath test (UBT):

The UBT detects active H. Pylori infection because of the organism`s urease activity. UBTs are approved for making the initial diagnosis of infection and for confirmation of eradication after treatment.

The sensitivity and specificity of the UBT is above 90% False positive tests are rare in clinical practice but can potentially occur in patients with bad oral hygiene and in patients infected with other gastric urease positive bacteria including H. heilmannii. False negative results typically occur in patients who have recently taken bismuth, antibiotics, or PPIs. To optimize sensitivity of the UBT, patients should ideally discontinue PPI treatment for a minimum of 2 weeks before the test.

Stool Antigen Test:

This is also approved for both the diagnosis of active H. Pylori infection and for the documentation of successful treatment. The sensitivity of stool antigen testing is decreased with PPI, bismuth, and antibiotic use patients should be advised to stop these medications before testing.

Endoscopic Methods:

Methods for endoscopic diagnosis include histology, biopsy urease testing, and culture. In most situations, mucosal biopsies from the gastric antrum are adequate for this purpose. However, additional biopsies should be taken from the proximal stomach if the patient has recently used a PPI.

The accuracy of the test may be reduced by the presence of blood in the stomach. Recent antibiotic, PPI, and bismuth use all reduce test sensitivity and increase the chance of false negative results.

Histologic evaluation of gastric mucosal biopsies can achieve sensitivity and specificity of >95% for the diagnosis of H. Pylori infection, and has been considered by some to

be the gold standard for diagnosis.

Culture of H. Pylori from biopsy specimens is rarely used in routine clinical practice for the reasons already given. It is mainly used for the determination of antimicrobial sensitivity and resistance in patients with 2 or more failed attempts at eradication.

TREATMENT OF H.PYLORI INFECTION

For first line therapy, the 2007 ACG guidelines recommended clarithromycin based triple therapy for 14 days or bismuth based quadruple therapy for 10 to 14 days. Clarithromycin based triple therapy typically consists of clarithromycin 500 mg bid, amoxicillin 1000 mg bid, and a PPI in standard does bid (although esomeprazole is FDA approved to be given qd for this indication).

Patients who are penicillin allergic should receive metronidazole 500 mg bid instead of amoxicillin. Clarithromycin should be avoided in patients previously treated with it (for H. Pylori infection or alternative indications) or another macrolide agent.

Bismuth based quadruple therapy typically comprises bismuth subsalicylate, metronidazole, tetracycline, and a PPI or an H2 receptor antagonist.

The ACG guidelines also suggested sequential treatment as a potential first line regimen although cautioned that this had not been validated within the United States. Sequential therapy was initially developed as a 10 day regimen that typically consists of a PPI and amoxicillin given bid for 5 days, followed by the same PPI, clarithromycin, and an imidazole (conventionally tinidazole rather than metronidazole) given bid for the next 5 days.

It proposed different initial treatment strategies based on an understanding of local clarithromycin resistance rates. For patients from low resistance areas, clarithromycin based triple regimens and bismuth based quadruple regimens were both recommended. For clarithromycin containing regimens, it was felt that the combinations of clarithromycin-PPI- amoxicillin and clarithromycin-PPI-metronidazole were equivalent. For patients from an area of high clarithromycin resistance, recommendations included bismuth-based quadruple therapy, sequential therapy, and nonbismuth quadruple therapy.

- As of 2014, FDA approved regimens for the treatment of H. Pylori infection include:

PPI-clarithromycin-amoxicillin.

- H2-receptor antagonist-bismuth-tetracycline-metronidazole.

- PPI-bismuth-tetracycline-metronidazole.

- "pylera" capsules (pylera contains bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride). with Omeprazole.

- Omeprazole-clarithromycin.

- Lansoprazole-amoxicillin.

The dual combination of Omeprazole and clarithromycin is not recommended based on problems with clarithromycin resistance. The dual combination of lansoprazole and amoxicillin remains potentially useful as its efficacy should not be influenced by clarithromycin resistance and as resistance to amoxicillin continues to be exceptionally rare in United State.

Concomitant Therapy

Also sometimes referred to as non-bismuth-based quadruple therapy, this is a 4 drug regimen consisting of a PPI, amoxicillin, clarithromycin, and metronidazole given together twice daily for the entire duration of therapy.

"LOAD" Therapy

This is a 4 drug regimen consisting of levofloxacin, Omeprazole, nitazoxanide, and doxycycline.

Second-line Regimens

If initial treatment with clarithromycin-based triple therapy fails, bismuth-based quadruple therapy should be used next. If initial treatment with bismuth-based quadruple therapy fails, clarithromycin-based triple therapy might be considered. Bismuth, amoxicillin, and tetracycline may all be used in second-line regimens even if used before as resistance is low to nonexistent.

Rescue Regimens (After Failure of 2 Different Regimens)

In 20% to 30% of patients, second-line treatment also fails. Rifabutin-based salvage therapy (consisting of rifabutin, a PPI, and amoxicillin) has reported eradication rates over 80%.

Other Potential Approaches to Improve Eradication Rates

1- Adjuvant Therapy

- The addition of probiotics to treatment regimens for H. Pylori may have an important role, although studies arecurrently limited.

- Adjuvant statin therapy (simvastatin) has shown promising results.

- some studies have suggested that the addition of vitamins E or C for 30days may increase eradication rates.

2- High-dose Dual Therapy (HDDT)

At DDW in 2014, the combination of rabeprazole 20 gm qid and amoxicillin 750 mg qid was significantly superior to both the standard and sequential regimens.

3- More Potent Acid Suppression

The potential availability of more powerful gastric antisecretory agents is at least promising. TAK- 438 is a potassium-competitive acid blocker (PCAB) that produces rapid and sustained suppression of intragastric acidity, or conventional PPIs in higher and/or more frequent doses, may introduce additional opportunities for tackling this infection with either 1 or 2 antibiotics. However, experience is currently limited.

To Conclude, H. Pylori infection is both common and important. We do not have a perfect treatment for it but we should strive to provide our patients with the most appropriate combination of medicines that we can. A few simple measures such as those outlined above could improve the current performance.