Helicobacter Pylori Eradication - First, Second And Third Line Of Drugs, Protocol

Helicobacter pylori eradication: which drug to choose?

Half a century ago, there were several theories offering their own version of the causes of gastric ulcer and intestinal ulcers. The turning point was 1979, when, as a result of scientific research, it was proved that the primary source of this problem is the bacterium Helicobacter pylori, which normally happily exists in the digestive tract of more than half of all representatives of humanity. Any decrease in immune defense is a good reason for the reproduction of colonies of Helicobacter pylori. For the treatment of heliobacteriosis, schemes have been created for the eradication of pathogenic bacteria from the human body.

Content:

• Scheme of eradication therapy Helicobacter pylori
• The first line of eradication of Helicobacter pylori
• The second line of eradication of Helicobacter pylori
• The third line of eradication of Helicobacter pylori
• The choice of drugs if it is necessary to conduct a repeated course of eradication therapy
• Treatment protocol for helicobacter pylori in adults

Scheme of eradication therapy Helicobacter pylori

When a doctor chooses an eradication therapy scheme in each specific case, the following factors must be taken into account:

• Therapy regimen;
• Predicted duration of treatment;
• The clinical picture of this case of heliobacteriosis;
• The cost of drugs included in the treatment regimen.

The Russian Gastroenterological Association and the Russian Group for the Study of Helicobacter pylori recommend taking as a basis a combined three-component therapy regimen that meets the following principles:

• Ability to eradicate bacteria in at least 80% of cases;
• Absence of side effects forcing the attending physician to cancel the treatment regimen, or provoking the patient to stop taking medications (up to 5% of such cases are allowed);
• effectiveness even with a short course no longer than 1-2 weeks.

The methodology for prescribing eradication therapy is based on the recommendations developed by the world community of gastroenterologists in Maastricht in 1996 and updated in 2000.

Recommendations of the Second Maastricht Agreement for anti-Helicobacter pylori therapy:

• In uncomplicated cases of peptic ulcer disease after a course of eradication therapy, the use of antisecretory drugs is not required.
• Indications for eradication therapy other than peptic ulcer: MALT lymphoma, atrophic gastritis, close family ties with a patient with stomach cancer, condition after resection for stomach cancer, patient's desire.

• Treatment of Helicobacter pylori infection should include the possibility of failure of the first line of eradication therapy and the need to use the second line if bacteria persist in the body. It is proposed to include 2 antibiotics in the first-line eradication regimen (triple therapy): Clarithromycin + Amoxicillin (or Metronidazole) and a proton pump inhibitor (or Ranitidine). It lasts no more than 7 days. In case of failure, it is recommended to use a second-line regimen (quadrotherapy), which includes 2 antibiotics: Tetracycline + Metronidazole, bismuth preparations and a proton pump inhibitor. The duration of the use of quadrotherapy is 7 days.
• At present, specific antibacterial drugs, probiotics and vaccines directed exclusively against Helicobacter pylori are not used in practice, they are still under development.

The developers of the Maastricht Recommendations excluded from the treatment regimen the usual combination for Russia: Amoxicillin + Metronidazole + proton pump blocker due to the increased resistance of Helicobacter pylori to nitroimidazole derivatives. Studies by Russian scientists have confirmed the low efficiency of this combination (only 30%). Russian gastroenterologists in first-line eradication therapy often use an affordable and effective triple therapy, which includes bismuth + Amoxicillin + Furazolidone preparations. The improvement of anti-Helicobacter pylori therapy continues. In 2005, modern schemes of eradication therapy of the first, second, third line were developed in the Netherlands.

The first line of eradication of Helicobacter pylori

The first-line three-component regimen gets its name from the fact that it consists of three drugs:

• antibiotic Clarithromycin,
• antibiotic Amoxicillin,
• a proton pump inhibitor based on Omeprazole, which regulates the activity of the acidic environment of gastric juice.

Proton pump inhibitors allow you to get rid of many negative manifestations of ulcers and gastritis caused by increased acidity of the stomach environment, as well as to avoid overly strict restrictions on the diet of a patient with peptic ulcer disease. Nevertheless, the restrictions still remain, although not so strict.

It is allowed to replace Amoxicillin with the antibiotic Nifuratel or Metronidazole. According to the indications, the gastroenterologist can prescribe a drug based on bismuth derivatives in scheme 4. Normally, such drugs are included in the second-line eradication scheme, but their properties have a positive effect on the course of the process of suppressing the inflammatory process. A protective coating forms on the surface of the stomach, relieving symptoms of inflammation and pain.

A lightweight scheme for elderly patients:

• Antibiotic Amoxicillin;
• Proton pump inhibitor;
• Bismuth preparation.

To increase the effectiveness of the standard first-line therapy, it is proposed to double the period of its application - from 7 to 14 days. The expected efficiency is up to 95%. If the treatment is ineffective, the doctor recommends switching to the second line of eradication therapy.

The second line of eradication of Helicobacter pylori

The four components of a second line eradication scheme are:

• 2 antibiotics: Tetracycline + Metronidazole, or Amoxicillin + a drug from the nitrofuran group;
• Proton pump inhibitor;
• Bismuth preparation.

Bismuth-based preparations are excellent cytoprotectors that restore the structure of cells of the gastric and intestinal mucosa and their resistance to the aggressive effects of acids and waste products of Helicobacter pylori. In addition, they have a bactericidal effect and reduce the risk of recurrence of heliobacteriosis to a minimum. When planning a second-line eradication regimen, it is not recommended to use previously used antibiotics. An effective, affordable and cheap quadrotherapy scheme with bismuth is also not without its drawbacks:

• A large number of pills taken (18 pieces per day);
• Frequent side effects;
• 4-fold dosing regimen.

To enhance the effectiveness of therapy with bismuth preparations, fruits, juices, milk are excluded from the diet during treatment. The duration of second-line therapy is 10-14 days.

The third line of eradication of Helicobacter pylori

It is extremely rare to switch to the third line of eradication therapy, but such a possibility still exists. Before starting the implementation of the third scheme, the patient is tested for the sensitivity of the Helicobacter pylori strain to antibiotics.

Line 3 drugs:

• Two antibiotics that have not been used before and have shown the highest degree of effectiveness in laboratory diagnostics;
• Bismuth preparations;
• Proton pump inhibitors.

Medicines based on bismuth (bismuth tripotassium dicitrate) have a complex effect:

• Relieve manifestations of dyspepsia (bloating, heartburn, gastralgia); act against Helicobacter pylori as an effective bactericidal agent;
• They stimulate the regeneration of damage to the deeper layers of the walls of the stomach.

Third-line therapy according to the Maastricht recommendations of the third convocation includes drugs from the group of rifamycins (Rifabutin) and quinolones (Levofloxacin). This combination was effective in 91% of cases. The resistance of Helicobacter pylori to Rifabutin is very low, therefore, its inclusion in the treatment protocol together with Amoxicillin and a proton pump inhibitor makes it possible to increase the effectiveness of therapy and even ignore the resistance of the bacterium to Metronidazole and Clarithromycin.

The choice of drugs if it is necessary to conduct a repeated course of eradication therapy

And the first, and second, and even the third regimen of Helicobacter pylori therapy may be ineffective when the percentage of eradication is 80% or less of cases of target achievement of the treatment goal. The effectiveness of treatment is reduced due to the bacteria's resistance to antibiotics, so researchers of the problem do not stop looking for the best regimens.

The resistance of Helicobacter pylori to Amoxicillin (less than 1%), to Tetracycline (close to 0) does not cause concern.

The number of resistant strains of bacteria to other antibacterial drugs:

• Clarithromycin - in Europe from 9.9 to 18%, in Moscow - 19.3% in adults, 28.5% - in children;
• To Metronidazole - in Europe from 20 to 40%, in Moscow - 54.8% in adults, 23.8% - in children

This is due to the frequent prescription of macrolide antibiotics in pediatric and therapeutic practice. Proton pump inhibitors, which create a favorable environment for the use of antibiotics in the gastrointestinal tract, are of no small importance in the success of eradication therapy. With the low quality of drugs in this group, the effectiveness of antibacterial agents also decreases.

Research is underway to add a probiotic to standard therapy to reduce stool frequency and flatulence.

A new scheme for eradication of bacteria has appeared - sequential therapy, which takes 10 days. It is used when the first line scheme fails.

In the first 5 days, take:

• Proton pump inhibitor - 2 times a day;
• Amoxicillin - 2000 mg / day.

In the next 5 days:

• Proton pump inhibitor - 2 times a day;
• Clarithromycin - 1000 mg / day;
• Tinidazole - 1000 mg / day.

According to the study, even in patients infected with Helicobacter pylori with high resistance to Clarithromycin, eradication increased from 29% to 89%. In the rest of the patients with unsuccessful first-line eradication, the indicator increased from 78% to 91%.

Treatment protocol for helicobacter pylori in adults

The main protocols for the eradication of Helicobacter pylori in adults, recommended by the 2016 Toronto and Maastricht Consensus:

No.	Protocol name	Protocol components	Duration	Indications
	Triple therapy	PPI - double dose of 0.04 g 2 r / day; Clarithromycin - 0.5 g 2 r / day; Amoxicillin - 1 g 2 r / day (or Metronidazole 0.5 g)	fourteen	1 line of eradication
	Standard Bismuth Quadrotherapy	PPI - standard dose 2 r / day; bismuth preparation 0.12 g 4 r / day; Tetracycline - 0.5 g 4 r / day; Metronidazole - 0.5 g 3 r / day	10-14	2 line of eradication in regions with low Hp resistance to Clarithromycin
	Optimizing Bismuth Quadrotherapy	PPI in double dose 2 r / day; bismuth preparation - 0.12 g 4 r / day; Tetracycline - 0.5 g 4 r / day; Metronidazole - 0.5 g 4 r / day	fourteen	The same
	Bismuth-free concomitant quadrotherapy	PPI - standard dose 2 r / day; Amoxicillin - 1 g 2 r / day; Clarithromycin - 0.5 g 2 r / day; Metronidazole - 0.5 g 2 r / day	ten	1 line of eradication or 2-3 lines if the previous ones are ineffective
five	Optimized concomitant therapy	Esomezaprozole 0.04 g 2 r / day Amoxicillin - 1 g 2 r / day; Clarithromycin - 0.5 g 2 r / day; Metronidazole - 0.5 g 2 r / day	fourteen	The same
	Optimized sequential therapy with Levofloxacin	Stage 1 - 5 days: Esomeprazole - 0.04 g 2 r / day; Amoxicillin - 1 g 2 r / day Stage 2 - 5 days: Esomeprazole - 0.04 g 2 r / day; Levofloxacin - 0.5 g 2 r / day; Tinidazole - 0.5 g 2 r / day	5 + 5	2 or 3 line of eradication
	Hybrid therapy	Stage 1 - 7 days: PPI in double dose 2 r / day; Amoxicillin - 1 g 2 r / day; Stage 2 - 7 days: PPI in a double dose - 2 r / day; Amoxicillin - 1 g 2 r / day; Clarithromycin - 0.5 g 2 r / day; Nitroimidazole - 0.5 g 2 r / day	7 + 7	2 or 3 line of eradication
eight	Triple therapy with Levofloxacin	PPI at a standard dose 2 r / day; Levofloxacin - 0.5 g 1-2 r / day; Amoxicillin - 1 g 2 r / day	10-14	2 or 3 line of eradication
nine	Quadrotherapy with Levofloxacin	Esomeprazole - 0.04 g 2 r / day; Amoxicillin - 1 g 2 r / day; Levofloxacin - 0.5 g once (or 0.25 g 2 r / day); Bismuth subcitrate - 0.24 g 2 r / day	fourteen	2-3 line of eradication
ten	Quadrotherapy with bismuth	PPI at a standard dose 2 r / day; bismuth preparation - 0.24 g 2 r / day; Amoxicillin - 1 g 2 r / day; Furazolidone - 0.01 g 3 r / day	fourteen	1, 2, 3 line of eradication
eleven	Triple therapy with Ribafutin	PPI in standard or double dose 1 g 2 r / day; Ribafutin - 0.03 g once (or 0.15 g 2 r / day)	ten	finishing option with unsuccessful attempts 1,2, 3 lines of eradication

To improve the effectiveness of treatment, it is recommended to use optimized eradication options - sequential and hybrid therapy. They include higher doses of PPIs (proton pump inhibitors), have a long course of treatment, and have more potent potential.

For treatment to be successful, it is important to educate the patient about the benefits of the treatment regimens used and the possible side effects.

Author of the article: Danilova Tatyana Vyacheslavovna | Infectionist

Education: in 2008 received a diploma in General Medicine (General Medicine) at the Pirogov Russian Research Medical University. Immediately passed an internship and received a diploma of a therapist