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H pylori antibiotic side effects: Side Effects of Prevpac (Lansoprazole, Amoxicillin and Clarithromycin), Warnings, Uses

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H. pylori Bacteria Infection: Symptoms, Diagnosis, Treatment, Prevention

Helicobacter pylori(H. pylori) is a type of bacteria. These germs can enter your body and live in your digestive tract. After many years, they can cause sores, called ulcers, in the lining of your stomach or the upper part of your small intestine. For some people, an infection can lead to stomach cancer.

Infection with H. pylori is common. About two-thirds of the world’s population has it in their bodies. For most people, it doesn’t cause ulcers or any other symptoms. If you do have problems, there are medicines that can kill the germs and help sores heal.

As more of the world gets access to clean water and sanitation, fewer people than before are getting the bacteria. With good health habits, you can protect yourself and your children from H. pylori.

How H. pylori Makes You Sick

For decades, doctors thought people got ulcers from stress, spicy foods, smoking, or other lifestyle habits. But when scientists discovered H. pylori in 1982, they found that the germs were the cause of most stomach ulcers.

After H. pylori enters your body, it attacks the lining of your stomach, which usually protects you from the acid your body uses to digest food. Once the bacteria have done enough damage, acid can get through the lining, which leads to ulcers. These may bleed, cause infections, or keep food from moving through your digestive tract.

You can get H. pylori from food, water, or utensils. It’s more common in countries or communities that lack clean water or good sewage systems. You can also pick up the bacteria through contact with the saliva or other body fluids of infected people.

Many people get H. pylori during childhood, but adults can get it, too. The germs live in the body for years before symptoms start, but most people who have it will never get ulcers. Doctors aren’t sure why only some people get ulcers after an infection.

Symptoms

If you have an ulcer, you may feel a dull or burning pain in your belly. It may come and go, but you’ll probably feel it most when your stomach is empty, such as between meals or in the middle of the night. It can last for a few minutes or for hours. You may feel better after you eat, drink milk, or take an antacid.

Other signs of an ulcer include:

Ulcers can bleed into your stomach or intestines, which can be dangerous to your health. Get medical help right away if you have any of these symptoms:

It’s not common, but H. pylori infection can cause stomach cancer. The disease has few symptoms at first, such as heartburn. Over time, you may notice:

  • Belly pain or swelling
  • Nausea
  • Not feeling hungry
  • Feeling full after you eat just a small amount
  • Vomiting
  • Weight loss for no reason

Getting a Diagnosis

If you don’t have symptoms of an ulcer, your doctor probably won’t test you for H. pylori. But if you have them now or have in the past, it’s best to get tested. Medicines like nonsteroidal anti-inflammatory drugs (NSAIDs) can also damage your stomach lining, so it’s important to find out what’s causing your symptoms so you can get the right treatment.

To start, your doctor will ask you about your medical history, your symptoms, and any medicines you take. Then they’ll give you a physical exam, including pressing on your belly to check for swelling, tenderness, or pain. You may also have:

  • Tests of your blood and stool, which can help find an infection
  • Urea breath test. You’ll drink a special liquid that has a substance called urea. Then you’ll breathe into a bag, which your doctor will send to a lab for testing. If you have H. pylori, the bacteria will change the urea in your body into carbon dioxide, and lab tests will show that your breath has higher than normal levels of the gas.

To look more closely at your ulcers, your doctor may use:

  • Upper gastrointestinal endoscopy. In a hospital, a doctor will use a tube with a small camera, called an endoscope, to look down your throat and into your stomach and the upper part of your small intestine. The procedure may also be used to collect a sample that will be examined for the presence of the bacteria. You may be asleep or awake during the procedure, but you’ll get medicine to make you more comfortable.
  • Upper GI tests. In a hospital, you’ll drink a liquid that has a substance called barium, and your doctor will give you an X-ray. The fluid coats your throat and stomach and makes them stand out clearly on the image.
  • Computed tomography (CT) scan. It’s a powerful X-ray that makes detailed pictures of the inside of your body.

If you have H. pylori, your doctor may also test you for stomach cancer. This includes:

  • Physical exam
  • Blood tests to check for anemia, when your body doesn’t have enough red blood cells. It could happen if you have a tumor that bleeds.
  • Fecal occult blood test, which checks your stool for blood that’s not visible to the naked eye
  • Endoscopy
  • Biopsy, when a doctor takes a small piece of tissue from your stomach to look for signs of cancer. Your doctor may do this during an endoscopy.
  • Tests that make detailed pictures of the insides of your body, such as a CT scan or magnetic resonance imaging (MRI)

Treatment for H. pylori

If you have ulcers caused by H. pylori, you’ll need treatment to kill the germs, heal your stomach lining, and keep the sores from coming back. It usually takes 1 to 2 weeks of treatment to get better.

Your doctor will probably tell you to take a few different types of drugs. The options include:

  • Antibiotics to kill the bacteria in your body, such as amoxicillin, clarithromycin (Biaxin), metronidazole (Flagyl), tetracycline (Sumycin), or tinidazole (Tindamax). You’ll most likely take at least two from this group.
  • Drugs that reduce the amount of acid in your stomach by blocking the tiny pumps that produce it. They include dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), or rabeprazole (Aciphex).
  • Bismuth subsalicylate, which may also help kill H. pylori along with your antibiotics
  • Medicines that block the chemical histamine, which prompts your stomach to make more acid. These are cimetidine (Tagamet), famotidine (Fluxid, Pepcid), nizatidine (Axid), or ranitidine (Zantac).

Your treatment could mean you’ll take 14 or more pills per day for a few weeks, which seems like a lot of medicine. But it’s really important to take everything that your doctor prescribes and to follow their instructions. If you don’t take antibiotics the right way, bacteria in your body can become resistant to them, which makes infections harder to treat. If your medications bother you, talk to your doctor about your treatment options and how you can handle side effects.

About 1-2 weeks after you finish your treatment, your doctor may test your breath or stool again to make sure the infection is gone.

Prevention

You can protect yourself from getting an H. pylori infection with the same steps you take to keep other germs at bay:

  • Wash your hands after you use the bathroom and before you prepare or eat food. Teach your children to do the same.
  • Avoid food or water that’s not clean.
  • Don’t eat anything that isn’t cooked thoroughly.
  • Avoid food served by people who haven’t washed their hands.

Though stress and spicy foods don’t cause ulcers, they can keep them from healing quickly or make your pain worse. Talk to your doctor about ways to manage your stress, improve your diet, and, if you smoke, how you can get help to quit.

What can I expect after H. pylori infection?

Most ulcers caused by H. pylori will heal after a few weeks of treatment. If you’ve had one, you should avoid taking NSAIDs for pain, since these drugs can damage your stomach lining. If you need pain medicine, ask your doctor to recommend some.

Where can I find information or support?

You can find information about H. pylori infection and ulcers from the American College of Gastroenterology. For information on stomach cancer, as well as online and local support groups, visit the American Cancer Society.

What are the adverse effects of medical treatments for Helicobacter pylori (H pylori) infection?

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  • Common side effects of Helicobacter pylori eradication therapy. 

    Background
    One of the most common reasons for poor medication adherence and associated treatment failure of triple therapy is adverse drug effect (ADEs) of medications.

    Objective
    Assessment of ADEs and associated factors during H. pylori eradication therapy.

    Method
    Consented H. pylori positive adult outpatients on standard triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) were involved in this facility based follow up study from May 2016 to April 2018 at Bahir Dar city in Ethiopia. Pre-developed questionnaire and formats were used to collect sociodemographic, medical information, and patient practice data before, during, and after therapy. Bivariate and backward stepwise multivariate logistic regression was used to analyze data. P-value < 0.05 at 95%CI was considered as significant.

    Result
    A total of 421 patients were involved in the study. Almost 80% of the patients were urban residents. Mean (±SD) age and body weight of patients were 30.63 (± 10.74) years and 56.79 (± 10.17) kg, respectively. ADE was reported from 26.1% of the patients and of all the reported ADEs, more than 85% was manifested with gastrointestinal symptoms which include gastrointestinal discomfort(39. 1%), nausea (13.6%), constipation(12.7%), diarrhea(12.9%) and anorexia(10%). Determinants of self-reported ADEs among patients in the present study were body mass index above 25 (AOR: 2.55; 95%CI (1.21–5.38), p = 0.014), duration of acid-pepsin disorder more than 3weeks (AOR: 3.57; 95%CI (1.63–7.81), p = 0.001), pain feeling during long interval between meals (AOR: 2.14; 95%CI (1.19–3.84), p = 0.011), and residence in urban area (AOR: 1.95; 95% CI (1.04–3.67), p = 0.038).

    Conclusion
    Significant proportion of patients reported ADEs which commonly manifested with gastrointestinal symptoms. Consideration of patients’ body mass index, duration of the disorder, period of the day when patients feel pain, and patients’ area of residence could help to reduce ADEs experienced during H. pylori eradication therapy.

    Helicobacter Pylori | Patient

    What is Helicobacter pylori infection and who is affected by it?

    Helicobacter pylori (commonly just called H. pylori) is a germ (bacterium). It can infect the lining of the stomach and duodenum (the first part of the intestine). Over half the world’s population has it. It is more common in developing countries. Why and when people become infected is unknown. It is sometimes present in children and some scientists believe we acquire it at a very young age. About 15 in 100 people are infected in the UK and it is becoming less common as time goes by. Once you are infected, unless treated, the infection usually stays for the rest of your life.

    Who should be tested for Helicobacter pylori and treated if it is found?

    If you have repeated indigestion symptoms (recurring dyspepsia)

    If you have recurring dyspepsia (dyspepsia which clears up and then comes back again), it is common practice to test for H. pylori before doing any other tests. If H. pylori is found, eradication treatment is often given. The exact diagnosis may not be known. For example, it might not be clear if the dyspepsia is caused by a duodenal or stomach ulcer, or non-ulcer dyspepsia. These can only be confirmed by having a look down into the gut with a test called gastroscopy (endoscopy). However, if symptoms go after treatment for H. pylori then that is the end of the matter. You do not need further tests such as gastroscopy. You will not know exactly what caused the symptoms but this does not matter if the symptoms have gone.

    Other reasons for testing

    If you are in one of the following groups, you may be offered a test for H. pylori and offered treatment with eradication therapy if it is found. If you:

    • Have a duodenal or stomach ulcer. Eradication therapy will usually cure the ulcer.
    • Have non-ulcer dyspepsia. Eradication therapy may work and clear symptoms but it does not in most cases.
    • Have a first-degree relative (mother, father, brother, sister or child) who has been diagnosed with stomach cancer. Treatment is advised even if you do not have any symptoms. The aim is to reduce your future risk of stomach cancer.
    • Are taking, or are about to take, long-term anti-inflammatory medication such as ibuprofen, diclofenac, aspirin, etc. The combination of these medicines and H. pylori increases the risk of developing a stomach ulcer.
    • Have a MALToma.
    • Have inflammation of the stomach lining (atrophic gastritis).
    • Have had an operation to remove a stomach cancer.
    • Have unexplained iron-deficiency anaemia.
    • Have a condition called chronic idiopathic thrombocytopenic purpura. This is an uncommon blood condition where the number of platelets in the blood becomes very low. Some research suggests a possible connection between H. pylori infection and this condition.

    What problems does Helicobacter pylori cause?

    Commonly there are no problems

    Most people who are infected with H. pylori have no symptoms or problems caused by the infection. These people do not know that they are infected. A number of H. pylori germs (bacteria) may just live harmlessly in the lining of the stomach and duodenum.

    Stomach and duodenal ulcers

    H. pylori is the most common cause of duodenal ulcers and stomach (gastric ulcers). About 3 in 20 people who are infected with H. pylori develop an ulcer. An ulcer occurs where the lining of the stomach or duodenum is damaged by the acid made in the stomach and the underlying tissue is exposed.

    In some people H. pylori causes inflammation in the lining of the stomach or duodenum. This is called gastritis and may lead to other conditions such as vitamin B12 deficiency. In gastritis the mucous defence barrier appears to be disrupted in some way (and in some cases the amount of acid to be increased). This seems to allow the acid to cause inflammation and ulcers. 

    Non-ulcer dyspepsia

    This is a condition where you have recurrent bouts of indigestion (dyspepsia) which are not caused by an ulcer or inflammation. It is sometimes called functional dyspepsia. H. pylori is sometimes found in people with non-ulcer dyspepsia. Getting rid of H. pylori cures some cases but makes no difference in most cases. The cause of most cases of non-ulcer dyspepsia is not known.

    Stomach cancer

    The risk of developing stomach cancer is thought to be increased with long-term infection with H. pylori. However, it has to be stressed that the vast majority of people with H. pylori do not get stomach cancer. The increased risk is small. Your risk may be greater if you have H. pylori in addition to having a first-degree relative (mother, father, brother, sister or child) who has been diagnosed with stomach cancer.

    Gastric mucosa-associated lymphoid tissue lymphoma – a MALToma

    This is a rare and unusual type of stomach cancer. Infection with H. pylori is thought play a role in this condition developing.

    How is Helicobacter pylori diagnosed?

    Various tests can detect H. pylori:

    • A breath test can confirm that you have a current H. pylori infection. A sample of your breath is analysed after you take a special drink. Note: prior to this test you should not have taken any antibiotics for at least four weeks. Also, you should not have taken a proton pump inhibitor (PPI) or H2-receptor antagonist medicine for at least two weeks. (These are acid-suppressing medicines.) Also, you should not eat anything for six hours before the test. The reason for these rules is because the medication and food can affect the test result.
    • An alternative test is the stool antigen test. In this test you give a pea-sized sample of your stools (faeces) which is tested for H. pylori. Note: prior to this test you should not have taken any antibiotics for at least four weeks. Also, you should not have taken a PPI or H2-receptor antagonist acid-suppressing medicine for at least two weeks.
    • A blood test can detect antibodies to H. pylori. This is sometimes used to confirm that you are, or have been, infected with H. pylori. However, it can take up to a year for this test to become negative once the infection has cleared. So, it is no use to confirm whether treatment has cleared the infection (if this needs to be known). If needed, the breath test or stool antigen test is usually used to check if an infection has cleared following treatment.
    • Sometimes a small sample (biopsy) of the lining of the stomach is taken if you have a gastroscopy (endoscopy). The sample can be tested for H. pylori.

    How is Helicobacter pylori cleared from the stomach and duodenum?

    H. pylori is killed by certain antibiotics. However, a combination of medicines is needed to get rid of it completely. This is referred to as combination therapy although because it gets rid of (eradicates) the germ it is also referred to as eradication therapy. You need to take two antibiotics at the same time. In addition, you need to take a medicine to reduce the acid in the stomach. This allows the antibiotics to work well in the stomach. You need to take eradication therapy for a week. It is important to take all the medication exactly as directed and to take the full course.

    Eradication therapy clears H. pylori in up to 9 in 10 cases if it is taken correctly for the full course. If you do not take the full course then the chance of clearing the infection is reduced. A second course of eradication therapy, using different antibiotics, will usually work if the first course does not clear the infection.

    Eradication therapy is sometimes called triple therapy as it involves three medicines – two antibiotics and an acid-suppressing medicine.

    Follow-up

    If you have indigestion (dyspepsia), it is usually only necessary to check to see if the H. pylori has gone if your symptoms come back after treatment. If you have a gastric or duodenal ulcer, testing is usually done 6-8 weeks after treatment.

    Are there any side-effects of eradication therapy?

    Up to 3 in 10 people develop some side-effects when they take eradication therapy. These include indigestion (dyspepsia), feeling sick (nausea), diarrhoea and headaches. However, it is worth persevering with the full course if side-effects are not too bad. A switch to a different set of medicines may be advised if the first combination does not clear the H. pylori, or if it caused bad side-effects and you had to stop taking it.

    Helicobacter pylori eradication: efficacy and side effect profile of a combination of omeprazole, amoxycillin and metronidazole compared with four alternative regimens | QJM: An International Journal of Medicine

    We evaluated eradication of Helicobacter pylori infection in 263 patients by a new 14-day regimen of omeprazole 40 mg mane (a gastric secretory inhibitor) plus two antibiotics: amoxycillin 500 mg three-times daily (tds) plus metronidazole 400 mg tds. The comparative groups included updated results of our previous work with a 14-day course of either standard triple therapy (STT, colloidal bismuth subcitrate 120 mg four times daily (qds) plus tetracycline 500 mg qds and metronidazole 400 mg tds), omeprazole 40 mg once daily plus amoxycillin 500 mg tds (OA), or two modified triple therapy: either Borody’s (BTT) of all three components (colloidal bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 200 mg) qds instead of tds, or Logan’s (ITT) seven-day therapeutic regimen of colloidal bismuth subcitrate 120 mg qds, amoxycillin 500 mg qds and, for the last three days, metronidazole 400 mg five times daily.

    Omeprazole/amoxycillin/metronidazole (OAM) therapy was better tolerated than STT (course completion 98.1% vs. 81.4%, p < 0.001). H. pylori was eradicated by OAM therapy in 53/55 (96.4%) patients with metronidazole-sensitive organisms and in 54/72 (75.0%) with metronidazole-resistant isolates (p < 0.01). The respective corresponding rates for STT and OA therapy were 20/22 (90.9%) and 14/29 (48.3%), (metronidazole-sensitive organisms) and 7/21 (33.3%) and 15/31 (48.4%) (infections resistant to metronidazole).

    BTT and LTT were also better tolerated than STT. The eradication rate for BTT was 23/26 (88.5%) but that for LTT, the best tolerated of the five treatment regimens, was only 19/28 (67.9%) when pretreat-ment isolates were metronidazole-sensitive. OAM therapy was better tolerated than either STT or BTT. With metronidazole-sensitive organisms, all three regimens eradicated about 90% of the organisms, although in our hands LTT was significantly less effective (67. 9%). In patients infected with metronidazole-resistant organisms, OAM therapy was significantly (p < 0.01) more effective than STT (95% Cl 19.2–64.2).

    These results support our current practice of prescribing OAM for patients with duodenal ulcer infected with H. pylori, reserving BTT for patients allergic to penicillin.


    This content is only available as a PDF.

    Efficacy and Tolerability of Two Quadruple Regimens: Bismuth, Omeprazole, Metronidazole with Amoxicillin or Tetracycline as First-Line Treatment for Eradication of Helicobacter Pylori in Patients with Duodenal Ulcer: A Randomized Clinical Trial

    Abstract

    Aim

    To evaluate the efficacy and tolerability of tetracycline vs. high-dose amoxicillin in bismuth-based quadruple therapy for Helicobacter pylori(H. pylori) eradication.

    Methods

    This randomized, open-label clinical trial included 228 patients with H. pylori infection and duodenal ulcer without a history of H.pylori treatment. Patients were randomly divided into two groups. The amoxicillin group received metronidazole 500mg, bismuth subcitrate 240mg, and amoxicillin 1000mg, all three times a day, plus omeprazole 20 mg twice a day, for 14 days. The tetracycline group received metronidazole 500mg three times a day; bismuth subcitrate240mg and tetracycline HCl 500mg, both four times a day; and omeprazole 20 mg twice a day, for 14 days. Evaluation for compliance and drug-relatedadverse effects were evaluated at the end of two weeks. Eight weeks after the end of treatment, the rate of H.pylori eradication was assessed by the C13urease breath test.

    Results

    There were no significant demographic differences between the two groups. Eradication rate was higher with the amoxicillin-containing regimen than the tetracycline-containing regimen: 105/110 (95.51%; 95% confidence interval, 91. 5%–99.3%) vs. 88/105 (83.8%; 95%CI, 76.7%–90.8%) by per-protocol analysis (p = 0.005) and 92.9% (95%CI, 88.1%–97.6%) vs. 76.5% (95%CI, 68.7%–84.2%) by intention-to-treat analysis (ITT, p = 0.001). Adverse effects were significant higher in the tetracycline groupthan in the amoxicillin group (65.2% vs. 43.4%; p = 0.001).

    Conclusion

    Bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole achieved an acceptable rate of H.pylori infection eradication with good tolerance in patients with duodenal ulcer. This regimen can overcome treatment resistance in areas with high prevalence of metronidazole and clarithromycin resistance.

    Trial registration

    The Thai Clinical Trial Registry (TCTR) 20170623004

    Citation: Salmanroghani H, Mirvakili M, Baghbanian M, Salmanroghani R, Sanati G, Yazdian P (2018) Efficacy and Tolerability of Two Quadruple Regimens: Bismuth, Omeprazole, Metronidazole with Amoxicillin or Tetracycline as First-Line Treatment for Eradication of Helicobacter Pylori in Patients with Duodenal Ulcer: A Randomized Clinical Trial. PLoS ONE 13(6):
    e0197096.

    https://doi.org/10.1371/journal.pone.0197096

    Editor: John Green, University Hospital Llandough, UNITED KINGDOM

    Received: October 12, 2017; Accepted: April 26, 2018; Published: June 11, 2018

    Copyright: © 2018 Salmanroghani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Data Availability: All relevant data are within the paper and its Supporting Information files.

    Funding: The author(s) received no specific funding for this work.

    Competing interests: The authors have declared that no competing interests exist.

    Introduction

    Helicobacter pylori(H. pylori) is a gram-negative bacterium that infects approximately 50% of people in industrialized nations and up to 80% in less-developed countries[1]. H. pyloricauses peptic ulcer disease, chronic gastritis, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma[2]. Although the bacterium is susceptible to most antimicrobial agentsinvitro, successful treatment of H.pyloriremains a challenge[3].Factors contributing to success inH. pylori treatment are drug efficacy, host compliance, and bacterial resistance[1, 2]. Resistance to commonly used drugs such as metronidazole and clarithromycin, is the most important reason for treatment failure of current regimens[1]. Emerging evidence shows high resistance to clarithromycin in countries with high consumption of macrolidederivatives[4], whereas regimen containing clarithromycin was reported to achieve 80% eradication rate[5]. Previous studies from our region (Iran)revealed that more than 20% of H. pylori isolates were resistant to clarithromycin and that over 50% of the H. pylori isolates were resistant to metronidazole [6–8].

    Due to high resistance to metronidazole and clarithromycin, regimens containing these antibiotics are not efficient[9]. In some studies on patients with metronidazole- and clarithromycin-resistantH. pylori, bismuth-based quadruple therapy was reported as a preferable regimen for eradication of H. pylori[10, 11]. This bismuth-based quadruple therapy includesbismuth, a proton pump inhibitor (PPI), and tetracycline together with metronidazole or tinidazole, with proper doses and duration. Quadruple regimen with suboptimal metronidazole doses (<1500 mg/day) was reported to achieve an overall eradication rate of 70% [3,4]. Increasing the dose of metronidazole in bismuth-based quadruple therapy was the first step in increasing eradication rates to acceptable levels, and bismuth compound was reported to be necessary for such response [12, 13]. However, low compliance,as well as increased side effects, are major issues that arise if full-dose metronidazole and tetracycline are used. There is also some evidence suggesting an increase in H.pylori resistance to tetracycline [14–16].

    Outcomes with substitution of tetracycline with amoxicillin in bismuth-based quadruple therapy have not been widely studied, especially in countries with high H.pylori resistance to metronidazole and clarithromycin such as Iran. Our pilot study revealed that a very good H.pylori eradication rate could be achieved with a modified bismuth-based quadruple therapy containing high-dose amoxicillin (3 g/day), adequate-dose metronidazole (1.5 g/day), and a PPI.Therefore, this open-label, randomized clinical trial was designed to compare the classic bismuth-based quadruple regimen containing metronidazole (1500mg/day) with a modified bismuth-based quadruple therapy containing high-dose amoxicillin (3 g/day), metronidazole (1. 5 g/day),and a PPI, with the aim to compare eradication rates, adverse effects, and patient compliance.

    Materials and methods

    Patient population

    This was a prospective, randomized, open-label clinical trial study conducted at ShahidSadoughi University (SSU) of Medical Center, a tertiary care hospital located in Yazd, Iran. Criteria for inclusion in this study were as follows: no history of treatment for H.pylori eradication, age above 18 years, endoscopically confirmed diagnosis of duodenal ulcer, and positive rapidureasetest. Patients with a history of previous gastric surgery, allergy to antibiotics, those who were treated with antibiotics in the preceding eight weeks,those with major systemic disease, and those who were pregnantor lactating were excluded from the study. The primary endpoint was H.pylori eradication ratebyintention-to-treat (ITT) analysis. The secondary endpoint was frequency of adverse effects and treatment compliance.

    Registration

    Ethics approval for this study was obtained from Yazd University Medical Sciences ethics committee on September 20, 2014, prior to patient enrollment. The clinical trial registration was completed retrospectively several months after patient enrollment was started, due to a miscommunication with the institution. We emphasize that our study begins and progress with complete consideration of ethicalrules. The authors confirm that all ongoing and related trials related to this study are registered.

    Intervention

    Patients were enrolled between October 20, 2014 and July 15, 2016. After the patients provided consent to participate in this trial, they were randomly assigned at a 1:1 ratio to receive one of the following two treatment regimens. The amoxicillin group (group I) received metronidazole 500mg, amoxicillin 1000mg, bismuth subcitrate 240mg, all three times a day, plus omeprazole 20mg twice a day, for 14 days. The tetracycline group (group II) received omeprazole 20mg twice a day; bismuth 240 mg, and tetracycline HCl500 mg, both four times a day;and metronidazole 500 mg three times a day, for 14 days. Omeprazole and bismuth were taken before meals, and antibiotics were used after meals. All patients were instructed on potential adverse effects and kept under observation during treatment for evaluation of adverse effects and compliance. All patients were requested to record any adverse effects that occurred during therapy, including bad taste, diarrhea, dizziness, weakness, nausea, loss of appetite, vomiting, fatigue, fever, and skin rash. Severe adverse effects were defined as those that would be considered to disrupt daily activities that required treatment discontinuation by the patient.

    Outcomes

    For evaluation for the primary outcome of H. pylori eradication rate, patients were asked to stop the PPI or the h3 blocker for at least four weeks before follow-up evaluation. Eight weeks after conclusion of the two-week study treatment, patients were assessed by the C13urease breath test by personnel who were blinded to the treatment, and a value of less than 4% was defined as successfulH. pylori eradication. For evaluation of secondary outcomes, data on adverse effects were collected through a standard sideeffect questionnaire, and good compliance was defined as ingesting more than 80% of the total number of doses included in the regimen.

    Sampling and blinding

    Sample size for the trial was calculated based on the following assumptions. Average rate of successfully achieved eradication of H.pyloriwith the standard quadruple therapy was 80% [17]. Based onourpilot study results showing an H.pylori eradication rate of 94% with the modified bismuth-based quadruple therapy containing high-dose amoxicillin (3 g/day),adequate-dose metronidazole dose (1.5 g/day) and omeprazole, we chose a two-sided alpha value of 0.05, and a power of 80%.Based on these assumptions at least 208 participates (104 subjects in each groups) would be required. In order to accommodate a 10% rate of lost to follow-up, we enrolled 228 patients.

    Statistical methods

    All registered data were analyzed using SPSS software version 22 for Windows (SPSS, Chicago, IL). Data were presented as means with standard deviation (SD), frequencies, and percentages. The chi-square and Fisher’s exact tests were used for comparison of categorical data between the two groups. P values of less than 0.05 were considered significant for all analyses. ITT and per-protocol (PP)analyses were performed to calculate eradication rates. The ITT analysis included all randomized patients. Individuals who did not take at least 80% of the drugs andthosewith unknown post-treatment H. pylori status were excluded from the PP analysis. Odds ratios with 95% confidence intervals (CIs) were calculated where appropriate.

    Ethical consideration

    This study was approved by the Ethics Committee of ShahidSadoughiUniversityof Medical Sciences in Yazd, Iran and registered with the protocol number ˮIr.ssu.rec.1394. 13712”on September 20, 2014. Participants provided written informed consent and were included in the study after they were provided information on treatment methods. This trial was also registered with Thai Clinical Trial Registry (Number: TCTR20170623004). The Consort 2010 checklist, the study protocol and the Ethic approval of study are given S1 Checklist, S1 File and S2 File.

    http://dx.doi.org/10.17504/protocols.io.mdjc24n

    Results

    Patient characteristics and compliance

    A total of 228 patients who were eligible were recruited from the SSU Gastroenterology Department. There were no significant differences in baseline characteristics including age and sex between the two treatment groups (Table 1). All patients except those who were lost to follow-up and those who could not tolerate the regimen were assessed by the C13urease breath test after the conclusion of treatments. The CONSORTflow diagram is depicted in Fig 1.

    H. pylori eradication rates

    Overall, the eradication rate by per-protocol analysis was 105/110 (95. 51%; 95%CI, 91.5%–99.3%) in group I and 88/105 (83.8%; 95%CI, 76.7%–90.8%) in group II, which was significantly different between the two treatment groups (p = 0.005). As presented in Table 2, the ITT analysis also revealed that the eradication rates were significantly different between the amoxicillin and tetracycline groups (92.9%; 95%CI, 88.1%–97.6% and 76.5%; 95%CI, 68.7%–84.2%, respectively; p<0.001). These results clearly showed that the H. pylori eradication rate was significantly higher in the amoxicillin group than in the tetracycline group.

    Adverse effects and compliance

    Overall, 4 patients in the tetracycline group and 2 patients in the amoxicillin group were lost to follow-up, and no outcome data were available for these patients. Additionally, 6 patients in the tetracycline group and 1 patient in the amoxicillin group could not tolerate the medication, i.e.,failed to take at least 80% of the prescribed medication, due to severe adverse effects that started a few days after initiation of the treatment. Adverse effects included tolerable diarrhea, bad taste, dizziness, weakness, nausea, skin rash, fever, fatigue, and vomiting, which were reported by 43.4% (49 of 113) of the patients in the amoxicillin group and 65.2% (75 of 115) of the patients in the tetracycline group, and adverse effects were significantly more frequent in the tetracycline group (p = 0.001). Bad taste was the most common side effect in both groups, whereas the frequency of vomiting was significantly higher in the tetracycline treatment group (4 vs. 0 in tetracycline vs.amoxicillin groups; p = 0.04).A summary of adverse effects in this study is presented in Table 3.

    Discussion

    Results of this open-label randomized study revealed that substitution of tetracycline with high-dose amoxicillin in classic bismuth-based quadruple therapy can increase H. pylori eradication rate and compliance in patients with duodenal ulcer. In patients who received high-dose amoxicillin in bismuth-based quadruple therapy, the eradication rates were 95. 6% and 92.9% by the PP and ITT analyses, respectively. Conversely, the eradication rates in patients who received classic bismuth-based quadruple therapy were 83.3% and 75% by PP and ITT analyses, respectively. These findings indicatedthat substitution of tetracycline with high-dose amoxicillin significantly increased the eradication rate not only by the ITT analysis but also the PP analysis.As more than 50% of H. pylori strains in Iran are resistant to metronidazole[6–8], amoxicillin might achieve better synergistic effects with metronidazole than tetracycline for eradication of metronidazole-resistantH. pylori strains. Additionally, patients had better tolerance to bismuth-based quadruple therapy containing amoxicillin instead of tetracycline.

    Generally, management of disorders associated with H. pylori infection requires treatment regimens that have eradication rates of more than 90% to 95%, if possible [18]. Use of similar effective first-line treatments is important not only for disease cure but also for prevention of secondary antibiotic resistance [19].

    A recent review of various regimens used as primary treatment in West Asia suggested that bismuth-furazolidone-metronidazole treatment for 10 days, clarithromycin-based hybrid treatment for 14 days, and classic bismuth-based quadruple therapy including PPIs, bismuth, tetracycline, and metronidazole for 14 days,wereequally effective [20]. Since the furazolidone-based regimen has many side effects, the regimen containing adequate-dose furazolidone (400mg/day) is not recommended [21, 22]. Due to high resistance to clarithromycin, clarithromycin-containing regimen isnot acceptable in our treatment course [23]. Potentially high resistance to levofloxacin also limits its use as front-line treatment [9, 23]. H. pylori culture and antibiogram are expensive, and lack of information on pretreatment susceptibility to antibiotics is the main reason for bismuth-based quadruple therapy as a primary regimen for eradication of H. pylori in our region, as recommended by the Toronto Consensus [24]. Malfertheiner and colleagues showed that in regions with high resistance to clarithromycin, quadruple treatment containing bismuth, metronidazole, tetracycline, and a PPI was preferable as the primary therapy for H. pylori eradication. Quadruple therapy achieves superior eradication with safety and tolerability comparable to those obtained with standard triple therapy [25]. In contrast to metronidazole, increase in clarithromycin dose was reported not to increase the eradication rate of clarithromycin-resistant H. pylori[26].

    Liang et al. concluded that four different bismuth-based quadruple treatments exhibited eradication ratesof>90% against H. pylori in subjects who were unresponsive to prior therapies, including those showing resistance to clarithromycin and metronidazole [27].Therefore, the two-week bismuth-based quadruple therapy containing high-dose metronidazole, a PPI, and tetracycline is a proper first-line treatment regimen in our patients with duodenal ulcer [28–30]. This regimen requires modifications with respect to drugs, doses, and duration to reach excellent H. pylori eradication rates. Bismuth and metronidazole are necessaryadditionsin this regimen. Increase in H. pylorieradication rate with an increased metronidazole dose is dependent on the presence of bismuth. Bismuth also improves the elimination ofH. pylori by triple therapy regimen [31]. In a systematic review and meta-analysis of 35 randomized clinical trials and 4763 subjects, the safety profile of bismuth was assessed, which revealed insignificant side effects in patients undergoing bismuth-based treatment [32].Emerging evidence of increasing resistance to tetracycline and reports demonstrating that adequate-dose metronidazole in combination with tetracycline results in more side effects raise concerns regarding substitution of tetracycline with another antibiotic.

    To achieve increased compliance to classic bismuth-based quadruple therapy, tetracycline was replaced with high-dose amoxicillin, based on several lines of evidence:In a recent study, high-dose amoxicillin (750mg four times a day) in combination with a potent PPI achieved a very good eradication rate, suggesting that amoxicillin is a unique anti-H. pylori antibiotic that has an acceptable eradication rate when used as part of a dual therapy containing a PPI [33, 34].The resistance rates to amoxicillin, metronidazole, and clarithromycin were about 2%, 44%, and 29% in America; 0.7%, 35%, and 18% in Europe; and 2%, 38%, and 21% in Asia, respectively [35]. H. pyloriwas found to rapidly acquire antibiotic resistance to clarithromycin, metronidazole, and levofloxacin but not to amoxicillin after a single course of anti-H. pylori therapy [36]. One potential explanation for the difference in acquired antibiotic resistance is that a single-point mutation can lead to resistance to clarithromycin, metronidazole, and levofloxacin, whereas multiple-site mutations are necessary to confer amoxicillin resistance [37–39]. A recent study among US male patients revealed increased resistance to clarithromycin and levofloxacin but no resistance to amoxicillin [40]. In Iran, 1.6%, 16.7%, and 57.5% ofH. pylori strainsshowed resistance to amoxicillin, clarithromycin, and metronidazole, respectively; however, no tetracycline resistance was reported [41]. However, this sensitivity pattern was found to have changed five years later, and there is an increasing resistance to tetracycline [42]. A recent study in Yazd, Iran revealed that H.pylori is more resistant to tetracycline than amoxicillin[43]. In a study in China, amoxicillin, in combination with metronidazole, bismuth, and lansoprazole, eradicated metronidazole-resistantH. pylori. In their study, Zhang et al. used 2g amoxicillin per day in combination with lansoprazole, metronidazole, and bismuth [44]. Lansoprazole, albeit more potent, is more expensive than omeprazole in Iran; therefore, high-dose amoxicillin with omeprazole was preferred over 2g amoxicillin with lansoprazole.

    The ITT analysis revealed an eradication rate of 92.92% in the amoxicillin group compared with the rate of 76. 5% in the tetracycline group, indicating that bismuth-based quadruple therapy containing tetracycline with adequate-dose metronidazole was associated with more adverse effects and intolerance. Unfortunately, severe adverse effects that lead to intolerance in the tetracycline group occurred 4–5 days after treatment initiation. In contrast, there were no severe drug-associated complications with the high-dose amoxicillin regimen, and the patient compliance was good.

    Inability to evaluate the H. pyloriantimicrobial resistance patterns was one of the main limitations of this study; howevera recent regional study indicated thatH. pylori resistance to tetracycline was more common than that to amoxicillin, which might explain the 16% failure rate in the tetracycline groupcompared to the 5% failure rate in the amoxicillin group based on the PP analysis[43].

    Conclusion

    The results of this randomized, open-label clinical trial revealed that a two-week bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole had an acceptable eradication rate with good tolerance in patients with duodenal ulcer and H. pylori infection. This therapy might overcome treatment resistance in areas with high prevalence of H. pylori resistance to metronidazole and clarithromycin.

    Acknowledgments

    We would like to thank the following staff members of the Gastroenterology Ward at ShahidSadoughi Hospital for their distinguished services: Mr. Dehmoubed, Mr. Ahmadi, Mrs. Ameri, and Mrs. Farhangfar.

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    21. 21.
      Roghani HS, Massarrat S, Shirekhoda M, Butorab Z. Effect of different doses of furazolidone with amoxicillin and omeprazole on eradication of Helicobacter pylori. Journal of gastroenterology and hepatology. 2003;18(7):778–82. pmid:12795748
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      Sadeghifard N, Seidnazari T, Ghafourian S, Soleimani M, Maleki A, Qomi MA, et al. Survey in Iran of clarithromycin resistance in Helicobacter pylori isolates by PCR-RFLP. Southeast Asian Journal of Tropical Medicine and Public Health. 2013;44(1):89. pmid:23682442
    23. 23.
      De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C, et al. Worldwide H. pylori antibiotic resistance: a systematic review. Journal of Gastrointestinal & Liver Diseases. 2010;19(4).
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      Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016;151(1):51–69. e14. pmid:27102658
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      Delchier J, Malfertheiner P, Thieroff‐Ekerdt R. Use of a combination formulation of bismuth, metronidazole and tetracycline with omeprazole as a rescue therapy for eradication of Helicobacter pylori. Alimentary pharmacology & therapeutics. 2014;40(2):171–7.
    26. 26.
      Murakami K, Sato R, Okimoto T, Nasu M, Fujioka T, Kodama M, et al. Eradication rates of clarithromycin‐resistant Helicobacter pylori using either rabeprazole or lansoprazole plus amoxicillin and clarithromycin. Alimentary pharmacology & therapeutics. 2002;16(11):1933–8.
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      Liang X, Xu X, Zheng Q, Zhang W, Sun Q, Liu W, et al. Efficacy of bismuth-containing quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone-resistant Helicobacter pylori infections in a prospective study. Clinical Gastroenterology and Hepatology. 2013;11(7):802–7. e1. pmid:23376004
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      Salazar CO, Cardenas VM, Reddy RK, Dominguez DC, Snyder LK, Graham DY. Greater than 95% success with 14‐day bismuth quadruple anti‐helicobacter pylori therapy: a pilot study in US Hispanics. Helicobacter. 2012;17(5):382–90. pmid:22967122
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    Nexium Hp7 [8944] – NPS MedicineWise

    What is in this leaflet

    This leaflet answers some of the common questions people ask about NEXIUM Hp7. It does not contain all the available information about NEXIUM Hp7.

    It does not take the place of talking to your doctor or pharmacist.

    All medicines have risks and benefits. Your doctor will have weighed the risks of you taking NEXIUM Hp7 against the benefits they expect it will have for you.

    If you have any concerns about taking these medicines, ask your doctor or pharmacist.

    Keep this leaflet with the medicines.
    You may need to read it again.

    What NEXIUM Hp7 is used for

    NEXIUM Hp7 is a combination pack, which contains three different medicines. When taken together in the right doses, they will kill the bacteria in your stomach called Helicobacter pylori and let your peptic ulcer heal.

    Depending on the position of the ulcer it is called a gastric or duodenal ulcer. A gastric ulcer occurs in the stomach. A duodenal ulcer occurs in the duodenum which is the tube leading out from the stomach.

    Most people who have a peptic ulcer also have a bacterium called Helicobacter pylori in their stomach. If the bacteria are killed it is unlikely that your ulcer will come back.

    NEXIUM is the brand name of esomeprazole (E), and it is given with amoxicillin (A), brand name Amoxil and clarithromycin (C), brand name Klacid. Amoxil and Klacid are both types of antibiotic.

    How NEXIUM Hp7 works

    NEXIUM is a type of medicine called a proton-pump inhibitor.

    NEXIUM works by decreasing the amount of acid made by the stomach, to give relief of symptoms and allow healing to take place. This does not stop food being digested in the normal way.

    Amoxicillin and clarithromycin are both antibiotics that help kill Helicobacter pylori. NEXIUM also helps kill the bacteria. When all three are taken together they are more effective than taken one or two at a time. It is possible that the antibiotics may not always kill Helicobacter pylori.

    Ask your doctor if you have any questions about why this medicine has been prescribed for you.
    Your doctor may prescribe this medicine for another use.

    There is no evidence that NEXIUM Hp7 is addictive.

    This medicine is available only with a doctor’s prescription.

    Before you take NEXIUM Hp7

    When you must not take it

    Do not take NEXIUM Hp7 if you have an allergy to:

    • any medicines containing esomeprazole, amoxicillin or clarithromycin
    • any ingredients listed at the end of the leaflet
    • any other similar medicines such as proton pump inhibitors, penicillins, cephalosporins or macrolide antibiotics

    Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

    Do not take NEXIUM Hp7 if you are taking any of the following medicines:

    • ergotamine
    • cisapride
    • pimozide
    • dihydroergotamine
    • astemizole
    • terfenadine
    • cilostazol
    • atazanavir
    • colchicine
    • simvastatin
    • lovastatin
    • ticagrelor
    • ranolazine
    • colchicine
    • oral midazolam
    • domperidone

    Please check with your doctor or pharmacist if you are taking any of these medicines. These medicines will be affected by the medicines in NEXIUM Hp7 and it is more likely you will get side effects.

    Do not take NEXIUM Hp7 if you have a history of heart conditions such as QT prolongation or ventricular cardiac arrhythmia.

    Do not take NEXIUM Hp7 if you have low potassium levels.

    Do not take NEXIUM Hp7 if you have both liver and kidney problems.

    NEXIUM Hp7 is not recommended for use in children.
    There is no information about the use of NEXIUM Hp7 in children.

    Do not take this medicine after the use by (expiry) date printed on the pack or if the packaging is torn or shows signs of tampering
    If it has expired or is damaged, return it to your pharmacist for disposal.

    If you are not sure whether you should start taking this medicine, talk to your doctor.

    Before you start to use it

    Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

    You must tell your doctor if you have:

    • problems with your blood
    • problems with your liver or kidneys
    • any heart conditions, such as QT prolongation or ventricular cardiac arrhythmia
    • you have glandular fever
    • myasthenia gravis, a condition in which the muscles become weak and tire easily
    • been diagnosed with osteoporosis
    • low potassium, low magnesium or any other electrolyte imbalances
    • if you have ever had a skin reaction after treatment with a medicine similar to NEXIUM that reduces stomach acid

    Tell your doctor if you are pregnant or plan to be pregnant, are breast-feeding or plan to breast-feed.
    It is not known if it is safe for you to take NEXIUM Hp7 if you are pregnant. The medicines in NEXIUM Hp7 may affect the developing baby.

    Your baby can take in all the medicines in NEXIUM Hp7 from breast milk if you are breast-feeding. NEXIUM Hp7 is not recommended when breast-feeding.

    Your doctor can discuss with you the risks and benefits of using NEXIUM Hp7 if you are pregnant or breast-feeding.

    If you have not told your doctor about any of the above, tell them before you start taking NEXIUM Hp7.

    Taking other medicines

    Do not take NEXIUM Hp7 if you are taking the following medicines:

    • ergotamine or dihydroergotamine – medicines used to treat migraine headaches
    • astemizole or terfenadine – medicines used to treat hayfever and allergies
    • atazanavir – a medicine used to treat Human Immunodeficiency Virus (HIV)
    • cilostazol – a medicine used to treat intermittent claudication
    • colchicine – a medicine used to treat gout
    • lovastatin or simvastatin – medicines used to treat high cholesterol
    • ticagrelor – a medicine used to treat blood clots
    • oral midazolam – a medicine used for surgical sedation
    • domperidone – a medicine used for nausea

    Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

    Some medicines and NEXIUM Hp7 may interfere with each other. These include:

    • diazepam, triazolam or alprazolam – medicines used as sedatives or to treat anxiety
    • ketoconazole, itraconazole, voriconazole or fluconazole – medicines used to treat fungal infections
    • warfarin and clopidogrel – medicines used to prevent blood clots
    • allopurinol or probenecid – medicines used to treat gout
    • phenytoin, sodium valproate or carbamazepine – medicines used to treat seizures
    • atorvastatin or rosuvastatin – medicines used to treat high cholesterol
    • theophylline – a medicine used to treat asthma
    • zidovudine, saquinavir, efavirenz, etravirine, nevirapine, nelfinavir or ritonavir – medicines used to treat HIV
    • insulin, repaglinide, nateglinide, pioglitazone or rosiglitazone – medicines used to treat diabetes
    • digoxin, quinidine or disopyramide – medicines used to treat heart conditions
    • citalopram, fluoxetine, clomipramine and imipramine – medicines used to treat depression
    • St John’s wort – a herbal remedy used to treat mood disorders
    • rifabutin, rifapentine, rifampicin or erythromycin – medicines used to treat bacterial infections
    • sildenafil, tadalafil or vardenafil – medicines used to treat impotence
    • tolterodine – a medicine used to treat incontinence
    • verapamil, amlodipine or diltiazem – medicines used to treat high blood pressure and some heart conditions
    • methylprednisolone – a corticosteroid
    • vinblastine – a medicine used to treat cancer
    • oral contraceptives or birth control pills. Talk to your doctor about the need for an additional method of contraception while on NEXIUM Hp7
    • tacrolimus or ciclosporin – medicines used to prevent organ transplant rejection or to treat certain problems with the immune system
    • methotrexate – a medicine used to treat arthritis and some types of cancer
    • erlotinib or related medicines used to treat cancer
    • phenobarbitone – a medicine used to treat epilepsy
    • tetracycline and aminoglycoside antibiotics – medicines used to treat certain infections
    • atypical antipsychotics – medicines used to treat psychiatric conditions, such as schizophrenia and bipolar disorder (e.g. quetiapine)
    • ibrutinib – a medicine used to treat cancer

    These medicines may affect NEXIUM Hp7 or may affect how well it works. You may need different amounts of your medicines or you may need to take different medicines.

    Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

    If you have not told your doctor about any of these things, tell them before you take any NEXIUM Hp7.

    How to take NEXIUM Hp7

    Follow all directions given to you by your doctor or pharmacist carefully.
    They may differ from the information contained in this leaflet.

    If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

    How much to take

    There are three different medicines in NEXIUM Hp7. It is very important that you take NEXIUM Hp7 exactly as follows:

    NEXIUM (esomeprazole) = E

    Take one 20 mg tablet in the morning and at night.

    Amoxil (amoxicillin) = A

    Take two 500 mg capsules in the morning and at night.

    Klacid (clarithromycin) = C

    Take one 500 mg tablet in the morning and at night.

    Morning

    1 E, 2 A, 1 C

    Night

    1 E, 2 A, 1 C

    How to take it

    Swallow the NEXIUM tablets whole with a glass of water. For patients with swallowing difficulties, the tablet can be placed in half a glass of non-carbonated water (mineral water is not suitable). The tablet may be gently mixed and care should be taken not to crush the tablet. Rinse the glass with half a glass of fluid and drink.

    NEXIUM tablets may also be administered, dispersed in non-carbonated water, through a gastric tube.

    Do not crush or chew the tablets as they will not work properly.

    Take medicines in NEXIUM Hp7 during or after meals.

    How long to take it

    Continue taking the capsules and tablets until you finish the course or until your doctor tells you to stop.
    If you do not complete the full course prescribed by your doctor, the Helicobacter pylori may not clear completely and your symptoms may return.

    Tell your doctor if your symptoms return.
    It is possible that the antibiotics may not kill Helicobacter pylori. You may need treatment with more antibiotics.

    If you forget to take it

    If you forget to take any of the medicines in NEXIUM Hp7 take it as soon as you remember, as long as it is more than four hours before the next dose of that medicine is due.

    Do not take a double dose to make up for any dose that you miss.

    If you are unsure what to do ask your doctor or pharmacist.

    If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

    If you take too much (overdose)

    Immediately telephone your doctor, the Poisons Information Centre (13 11 26) or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much NEXIUM Hp7 even if there are no signs of discomfort or poisoning.

    If you take too much NEXIUM Hp7 you may vomit and have severe stomach problems.

    While you are using NEXIUM Hp7

    Things you must do

    Take NEXIUM Hp7 exactly as your doctor has prescribed.

    If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking NEXIUM Hp7.

    If you become pregnant while you are taking NEXIUM Hp7, tell your doctor.

    If you get severe diarrhoea, tell your doctor, pharmacist or nurse immediately. Do this even if it occurs several weeks after NEXIUM Hp7 has been stopped.
    Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take medicine to stop the diarrhoea without first checking with your doctor.

    If you get a sore, white mouth or tongue while taking, or soon after stopping NEXIUM Hp7, tell your doctor. Also tell your doctor if you get vaginal itching or discharge.
    This may mean you have a fungal infection called thrush. Sometimes the use of NEXIUM Hp7 allows fungi to grow and the above symptoms to occur. NEXIUM Hp7 does not work against fungal infections.

    Tell any other doctors, dentists and pharmacists who are treating you that you are taking NEXIUM Hp7.

    If you need to have any medical tests while you are taking NEXIUM Hp7, tell your doctor.
    It may affect the results of some tests.

    Drink plenty of water or fluids while taking NEXIUM Hp7

    Things you must not do

    Do not take NEXIUM Hp7 to treat any other complaints unless your doctor tells you to.

    Do not stop taking NEXIUM Hp7, or change any of the doses, unless you have discussed it with your doctor.
    You need to take all the capsules and tablets in the pack for it to work properly. If you stop taking it, your ulcer may come back and be harder to treat next time.

    Do not give NEXIUM Hp7 to anyone else, even if they have the same condition as you.

    Things to be careful of

    Be careful driving or operating machinery until you know how NEXIUM Hp7 affects you.

    NEXIUM Hp7 may cause dizziness in some people. Make sure you know how you react to NEXIUM Hp7 before you do anything that may be dangerous if you are dizzy.

    Please talk to your doctor or pharmacist about these possibilities if you think they may bother you.

    Side effects

    Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking NEXIUM Hp7.

    NEXIUM Hp7 helps most people with peptic ulcer and Helicobacter pylori infection, but it may have unwanted side effects in a few people.

    All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

    Ask your doctor or pharmacist to answer any questions you may have.

    Tell your doctor if you notice any of the following and they worry you:

    • diarrhoea, nausea or vomiting
    • headache
    • dizziness
    • constipation
    • loss of appetite
    • stomach pain (e.g. cramps)
    • wind
    • dryness of the mouth or other body cavities
    • soreness of mouth or tongue
    • “pins and needles”
    • metallic taste or other change in taste or smell
    • chills
    • fatigue
    • excessive burping

    These side effects are usually mild.

    Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice the following:

    • muscle pain or weakness
    • increase in breast size (males)
    • fever
    • changes in sleep patterns
    • mood changes, hallucinations, confusion or depression
    • change in sexual function
    • blurred vision, hearing disturbances
    • hair loss
    • bleeding or bruising more easily than normal
    • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
    • skin rash
    • blood in urine
    • tremor
    • convulsions or fits
    • overgrowth of yeast infections (thrush)
    • fainting, irregular heart heat
    • yellowing of the eyes or skin

    These may be serious side effects. You may need urgent medical attention.

    If any of the following happen, stop taking NEXIUM Hp7 and tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

    • shortness of breath, wheezing or difficulty breathing
    • swelling of the face, lips, tongue or other parts of the body
    • chest pain
    • severe skin reaction which may include rash, itching, redness, blistering or peeling of the skin
    • severe upper stomach pain, with nausea and vomiting
    • signs of liver inflammation including yellowing of the skin or eyes, feeling generally unwell, nausea, vomiting, loss of appetite
    • skin reaction, especially in sun-exposed areas, with joint pain
    • severe stomach or abdominal cramps, watery and severe diarrhoea, which may also be bloody (this may occur several weeks after you stop taking NEXIUM Hp7)

    Do not take any medicine to stop the diarrhoea unless advised by your doctor.

    These are very serious side effects. If you have them, you may have had a serious reaction to one of the medicines in NEXIUM Hp7. You may need urgent medical attention or hospitalisation.

    Tell your doctor if you notice anything else that is making you feel unwell.
    Some people may get other side effects while taking NEXIUM Hp7.

    Do not be alarmed by this list of possible side effects.
    You may not experience any of them.

    After using NEXIUM Hp7

    Storage

    Keep the three medicines in NEXIUM Hp7 in their separate blisters until it is time to take them.

    Keep it in a cool dry place where the temperature stays below 25°C.

    Do not store it or any other medicine in the bathroom or near a sink.

    Do not leave it in the car on hot days.
    Heat and dampness can destroy some medicines.

    Keep it where young children cannot reach it.
    A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

    Disposal

    If your doctor tells you to stop taking them, or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

    Product description

    What NEXIUM Hp7 looks like

    NEXIUM tablets 20 mg are light pink, oblong shaped, marked with ’20 mg’ on one side and ‘A/EH’ on the other side.

    AMOXIL capsules 500 mg are red and yellow capsules, marked with ‘AM500’.

    KLACID tablets 500 mg are pale yellow, oval, film coated tablets.

    Ingredients

    Each NEXIUM tablet contains esomeprazole 20 mg as the active ingredient, plus:

    • glyceryl monostearate
    • hyprolose
    • hypromellose
    • magnesium stearate
    • methacrylic acid copolymer
    • microcrystalline cellulose
    • synthetic paraffin
    • macrogol 6000
    • polysorbate 80
    • crospovidone
    • sodium stearylfumarate
    • purified talc
    • triethyl citrate
    • sugar spheres (maize starch and sucrose)

    NEXIUM is provided in a blister wallet of 14 tablets.

    The tablets are coloured with titanium dioxide (CI77891), iron oxide red (CI77491) and iron oxide yellow (CI77492).

    Each AMOXIL capsule contains amoxicillin trihydrate 500 mg, plus:

    • magnesium stearate
    • purified talc

    Amoxil is provided in blister packs of 28 capsules.

    The hard gelatin capsule is coloured with titanium dioxide (CI77891), iron oxide yellow (CI77492), erythrosine (CI45430), indigo carmine (CI73015) and Tek Product – Tek Print SW-0012- White Ink.

    Each KLACID tablet contains clarithromycin 500 mg as the active ingredient, plus:

    • croscarmellose sodium
    • microcrystalline cellulose
    • povidone
    • silicon dioxide
    • hyprolose
    • hypromellose
    • purified talc
    • sorbitan mono-oleate
    • stearic acid
    • magnesium stearate
    • propylene glycol
    • sorbic acid
    • vanillin
    • titanium dioxide (CI77891)
    • quinoline yellow (CI47005)

    KLACID is provided in blister packs of 14 tablets.

    NEXIUM Hp7 does not contain gluten.

    Sponsors

    AstraZeneca Pty Ltd
    ABN 54 009 682 311
    66 Talavera Road
    Macquarie Park NSW 2113
    Telephone: 1800 805 342

    Aspen Pharmacare Australia Pty Ltd
    34-36 Chandos Street
    St Leonards NSW 2065

    Mylan Health Pty Ltd
    Level 1, 30 The Bond
    30-34 Hickson Road
    Millers Point NSW 2000

    Australian Registration Number:
    NEXIUM Hp7 – 281690

    This leaflet was prepared in March 2019.

    NEXIUM is a registered trade mark of the AstraZeneca group of companies.

    AMOXIL is a registered trade mark of the Aspen Global Inc. group of companies.

    KLACID is a registered trade mark of Mylan Health Pty Ltd.

    Doc ID-002262136 V12.0

    Published by MIMS May 2019

    Problems of treatment of Helicobacter pylori infection | Loranskaya I.D., Rakitskaya L.G., Mamedova L.D.

    Currently, the role of B.J. Marshall and R. Warren of the gram-negative helical bacterium Helicobaster pylori (H. pylori) in the development of many diseases of the gastrointestinal tract (GIT) [5, 6, 10]. The prevalence of H. pylori among the population in different countries reaches 50-80%, in Russia the infection with H. pylori in different regions is 70-80%, and in St.Moscow – 60–70% [6, 15]. Ways of transmission of infection: oral, through water and food, and contact – from person to person, more often between members of the same family through personal hygiene items. Many studies have confirmed the etiological role of H. pylori in the development of chronic atrophic gastritis (90-100%), gastric ulcer (PUD) (70-80%) and duodenal ulcer (90-100%), adenocarcinoma (80%) and stomach maltoma (40–75%) [4, 5, 7].

    Once in the stomach, the bacterium produces urease, which breaks down the urea of ​​the gastric contents, resulting in the formation of ammonia and CO2.Ammonia helps protect the microbe from hydrochloric acid and causes damage to the gastric mucosa. By releasing the enzyme mucinase, H. pylori destroys the mucin protein contained in the gastric mucus, which creates conditions for the penetration of the bacterium through the mucus layer and its adhesion to the epithelium of the gastric mucosa. H. pylori also secretes other enzymes: catalase, oxidase, protease, phospholipase and vacuolizing cytotoxin, which has a direct damaging effect on the epithelium of the gastric mucosa, enhancing cell apoptosis.Enzymes stimulate lipid peroxidation, which contributes to the inflammatory process in the gastric mucosa. Inflammation of the mucous membrane is accompanied by the infiltration of the lamina propria by neutrophils, plasma cells, lymphocytes, macrophages. Infiltration by neutrophils is stimulated by the secretion of interleukin-8, which is produced by epithelial cells in response to H. pylori. This effect is most pronounced in the pathogenesis of chronic atrophic gastritis and ulcer in Cag A and Vac A bacterial strains [2, 4, 7].
    Therefore, anti-inflammatory and anti-Helicobacter pylori therapy is justified in any disease associated with H. pylori. The main principle of the treatment of the above diseases is eradication therapy, the indications of which are determined by the Maastricht Consensus in 1996 and its revisions in 2000 (“Maastricht II”), 2005 (“Maastricht III”) and 2010 (“Maastricht IV” ) [sixteen].
    In addition to the indications for eradication therapy, according to Maastricht III, in addition to the main diseases, there are conditions after resection of the stomach for stomach cancer, as well as the appointment of treatment for persons who are first-line relatives of gastric cancer patients and persons infected with H.pylori without clinical manifestations, at the request of patients. In addition, it is possible to conduct anti-Helicobacter pylori therapy for diseases such as gastroesophageal reflux disease, functional dyspepsia, long-term use of non-steroidal anti-inflammatory drugs and unexplained iron deficiency anemia with the obligatory presence of H. pylori [11, 20, 21, 24].
    Depending on the degree of Helicobacter pyloriosis revealed during histological examination of a biopsy from the antrum of the stomach during gastroduodenoscopy, various eradication therapy schemes are recommended: 3- or 4-component for 7, 10 or 14 days [6, 8, 11, 21].
    The first line of anti-helicobacter (eradication) therapy includes several options. The first option is a proton pump inhibitor (PPI): omeprazole 20 mg 2 times / day or esomeprazole 20 mg 2 times / day, or lansoprazole 30 mg 2 times / day, or pantoprazole 40 mg 2 times / day, or rabeprazole 20 mg 2 r. / Day; amoxicillin 500 mg 4 times a day or 1000 mg 2 times a day in combination with clarithromycin 500 mg 2 times a day.
    The second option includes PPIs in the same doses, antibiotics amoxicillin and clarithromycin in the above doses, and bismuth tripotassium dicitrate 120 mg 4 r./ day or 240 mg 2 r. / day.
    The third option – in the presence of atrophic gastritis with achlorhydria, there is no PPI in the scheme, and amoxicillin 500 mg 4 r. / Day in combination with clarithromycin 500 mg 2 r. / Day + bismuth tripotassium dicitrate 240 mg 2 r. / Day is included.
    The fourth option is recommended for older people for whom standard anti-Helicobacter pylori therapy is limited. The scheme includes PPI in standard dosage + amoxicillin + bismuth tripotassium dicitrate or a short course of PPI + bismuth tripotassium dicitrate – 28 days (IV Moscow agreement) [7].
    The second line of anti-Helicobacter pylori therapy includes: the first option – PPI in standard doses, bismuth tripotassium dicitrate 240 mg 2 times / day, metronidazole 500 mg 3 times / day and tetracycline 500 mg 4 times / day.
    The second option is a PPI in a standard dosage, amoxicillin 500 mg 4 times a day or 1000 mg 2 times a day, bismuth tripotassium dicitrate 240 mg 2 times a day and furazolidone 100 mg 4 times a day.
    In the recommendations of “Maastricht III” it is proposed to prescribe quadrotherapy as the first line of treatment for Helicobacter pyloriosis and to lengthen the treatment period to 14 days.In this case, the effectiveness of eradication increases by 12% [4, 8]. In our country, there is an increasing resistance to clarithromycin and metronidazole due to the fact that the above drugs are widely prescribed for other inflammatory diseases. This led to the search for new alternative regimens, as well as to an increase in the duration of therapy [9, 14].
    However, the Maastricht Guidelines suggest keeping clarithromycin in 3- and 4-way regimens if the incidence of clarithromycin-resistant H. pylori is less than 15–20%.In case of resistance in a greater percentage of cases, it is recommended to replace the drug with another antibiotic – levofloxacin, 500 mg 2 r. / Day. According to the standards for the diagnosis and treatment of acid-related and H. pylori-associated diseases (IV Moscow Agreement), clarithromycin can be replaced with rifaximin 400 mg 2 times / day or josamycin 1000 mg 2 times / day [4, 7].
    With resistance to metronidazole in less than 40% of cases, the Maastricht recommendations suggest leaving metronidazole in any of the regimens or replacing it with furazolidone.If the percentage of resistance is higher, the drug is excluded from all therapy regimens and is replaced by nitrofuran drugs – furazolidone or nifuratel (IV Moscow Agreement, 2010).
    The third line of the Maastricht Recommendations – treatment is selected after determining the sensitivity of H. pylori to antibiotics.
    Maastricht IV offers another option for eradication – sequential 10-day therapy: PPI + amoxicillin – 5 days, then the next 5 days PPI + clarithromycin + metronidazole.The rest of the eradication regimens are 3-component and quadrotherapy without bismuth tripotassium dicitrate or with it in the same doses for a duration of treatment from 7 to 14 days [2].
    Control over the quality of anti-Helicobacter pylori therapy is carried out after 4-6 weeks. after the end of treatment. If H. pylori is detected, repeated courses of treatment are recommended with replacement of the proton pump blocker and antibiotic.
    Correctly selected anti-Helicobacter pylori therapy made it possible to reduce the progression of chronic gastritis and the frequency of recurrence of ulcer and its complications: bleeding, perforation, penetration and malignancy of gastric ulcers.
    However, there are also negative aspects of these eradication treatment regimens. This is, first of all, an increase in the resistance of H. pylori to antibiotics, the appearance of hypersensitivity reactions to antibiotics and other drugs in treatment regimens, and a violation of intestinal microbiocenosis. Problems associated with therapy for H. pylori infection include an unsatisfactory level of eradication and / or the development of side effects of treatment [9, 14].
    Antibiotic-associated diarrhea (AAD) is one of the most common complications.According to statistics, AAD is observed in 5-30% of patients receiving antibiotics. The term “antibiotic-associated diarrhea” is understood as diarrhea unexplained by other causes, which developed in connection with the appointment of antibiotics (during their administration or in the first 2 months after the end). The spectrum of clinical manifestations of AAD is wide: from pseudomembranous colitis to mild diarrhea. Complications of pseudomembranous colitis can be toxic megacolon, bowel perforation, sepsis, which in some cases requires colectomy.The greatest risk of developing AAD is observed while taking amoxicillin with clavulanic acid and cefixime. Ampicillin, amoxicillin, clindamycin, lincomycin, cephalosporins of the second and third generations are drugs, when taken, the most frequently observed AAD associated with Clostridium difficile [18]. In addition, Clostridium perfringens, Staphylococcus aureus, Candida spp., Klebsiella oxytoca, Salmonella spp. Are discussed as etiological factors for AAD.
    Unfortunately, not only antibiotics play an important role in the development of diarrheal syndrome when N.pylori. In recent years, a direct relationship between the suppression of hydrochloric acid and an increased risk of intestinal infection has been proven. Despite the undoubted positive role of PPIs and other antisecretory agents in the treatment of pathology of the esophagogastroduodenal zone, there is also a downside to the coin – the possibility of complications of this therapy, one of which is the risk of bacterial infections (pneumonia, Clostridium difficile AAD and other variants of infectious gastroenteritis). It has been proven that hypochlorhydria caused by prolonged use of PPIs can lead to bacterial colonization of the upper gastrointestinal tract and thereby affect the composition of the eubiotic microflora of the small intestine [19, 25].The vegetative form of Clostridium difficile survives in the stomach when the pH level rises, which explains the high risk of bacterial colonization of the small intestine in patients taking PPIs. This is supported by the finding that the possibility of developing Clostridium difficile colitis and its severity are the same in animals treated with PPIs or antibiotics.
    In recent years, taking into account the threat of AAD development during eradication therapy of H. pylori infection, probiotics have been prescribed for prophylactic purposes and to reduce the symptoms of diarrhea.The data of meta-analyzes of studies of the effectiveness of probiotics, conducted in 2010–2011, showed that the use of this group of drugs significantly accelerates the recovery of patients in the treatment of diarrhea of ​​various origins, incl. AAD. A decrease in the incidence of AAD occurs against the background of taking probiotic components at a dose of more than 5 billion CFU / day.
    An analysis of more than 11 thousand publications and the results of 622 clinical studies have confirmed the effectiveness of taking probiotics in adults during antibiotic treatment, incl.including and in the schemes of eradication therapy for H. pylori infection. The latest revision of Maastricht IV already sees the use of pre- and probiotics as promising: provision 12 of the Treatment section: “The use of certain pro- and prebiotics as adjuvant therapy has shown promising results in reducing the incidence of side effects.”
    In clinical practice, in most cases, probiotics containing bifidobacteria, lactobacilli, and Saccharomyces boulardii are used [22, 23]. In dynamics, it is mainly the clinical symptoms and the composition of the fecal microflora that are assessed.Researchers explain the positive role of probiotics from the standpoint of ensuring colonization resistance, immunomodulatory effect, as well as the possibility of stopping osmotic diarrhea while taking antibiotics, and optimizing the function of the intestinal epithelium.
    At the same time, the question of the survival of probiotic microorganisms in the gastrointestinal tract, their biocompatibility with indigenous microorganisms, the effect on the immune system of the body as a whole, and their resistance to antibiotics have not been resolved. In this regard, it is important to study the safety of probiotics, the contribution of each component of this class of immunobiological drugs.
    In recent years, evidence has been obtained that the main active component of the restoration of intestinal microflora in dysbiotic conditions is the metabolic products of probiotic microorganisms – their metabolites. Success in the treatment of recurrent Clostridium difficile diarrhea was also obtained as a result of a new original manipulation – intestinal microbiota transplantation – the introduction of a suspension of feces from healthy donors through a duodenal probe, which turned out to be more effective than treatment with vancomycin.In experiments on conventional white mice with experimental AAD, the effect of components of feces from healthy mice was studied when administered per os and per rectum. The most pronounced stimulating effect of restoring the intestinal microflora was provided by the orally administered filtered suspension of feces containing microbial metabolites. Thus, a promising direction in the correction of dysbiosis, prevention and treatment of AAD is the use of drugs – metabolite probiotics [16, 17].
    From these positions, the domestic synbiotic Bactistatin is of interest – a complex compound of pro- and prebiotic components.One of the main active principles of Bactistatin is the composition of Bacillus subtilis metabolites (bacteriocins, lysozyme, catalases), which have a bactericidal and bacteriostatic effect on pathogenic and opportunistic microorganisms. In addition, microbial metabolites have an immunomodulatory effect and optimize the state of the intestinal microbiota.
    The second component of Bactistatin is a natural sorbent zeolite, which provides sorption and elimination of toxins, normalizes intestinal motility, and is an additional source of microelements.
    Soy flour hydrolyzate as part of the complex is an additional source of protein and amino acids, contributing to the restoration of intestinal biocenosis. The effectiveness of using Baktistatin in the eradication therapy regimens for H. pylori infection has been proven by domestic clinicians [12, 26]. The positive effect of the drug on the intestinal microflora, antibiotic tolerance, and the success of eradication therapy were noted [3]. The possibility of prescribing Baktistatin from the first day of antibiotic therapy is also essential, since the drug is resistant to its action.When carrying out eradication treatment without the inclusion of a synbiotic, violations of the intestinal microbiocenosis were significantly more often observed [12, 13].
    Thus, the use of Bactistatin is promising in the prevention of one of the most frequent complications of eradication therapy – AAD, which allows us to hope for a successful treatment of H. pylori infection.

    Literature
    1. Bugaeva I.O., Grechushnikov V.B. and others. Helicobacter pylori: modern diagnostics and therapy. Saratov, 2008.105 p.
    2. Vyalov S.S. Peptic ulcer and Maastricht-4: introduction into clinical practice // Effective pharmacotherapy. Gastroenterology. 2012. No. 6. P. 16–23.
    3. Zaitseva E.V., Antonenko O.M. The place of dysbiosis correction in the treatment of a number of chronic diseases of the digestive tract // Consilium medicum. Gastroenterology. 2011. No. 1. S. 60–63.
    4. Ivashkin V.T., Sheptulin A.A., Lapina T.A. Chronic gastritis caused by Helicobacter pylori infection: diagnosis, clinical significance, prognosis.A guide for doctors. RGA. M., 2009.23 p.
    5. Isakov V.A., Domoradskiy I.V. Helicobacter pyloriosis. M .: Medpraktika-M, 2003.411 p.
    6. Lazebnik LB, Vasiliev Yu.V. et al. Helicobacter pylori: prevalence, diagnosis, treatment // Experimental and clinical gastroenterology. 2010. No. 2. P. 3–7.
    7. Lazebnik L.B., Bordin D.S. and other Chronic gastritis. Guidelines. Moscow: TsNIIG, 2011.34 p.
    8. Lapina T.L. Helicobacter pylori eradication therapy // Medical Bulletin.2006. No. 6. P. 9–10.
    9. Maev I.V., Vyuchnova E.S. and other Side effects of modern anti-Helicobacter pylori therapy // Clinical medicine. 2002. No. 6. P. 7–12.
    10. National Guide to Gastroenterology / ed. Ivashkina V.T., Lapinoy T.L. M .: GEOTAR-Media, 2008.704 p.
    11. Samsonov A.A., Maev I.V. Modern standards for the diagnosis and treatment of diseases associated with Helicobacter pylori. (analysis of materials of the 3rd Maastricht agreement) // Medical Bulletin.2006. No. 4. P. 358.
    12. Tkachenko E.I., Avalueva E.B. et al. Eradication therapy, including probiotics: a consensus of efficacy and safety // Clinical nutrition. 2005. No. 1. P. 14–20.
    13. Uspensky Yu.P., Baryshnikova N.V. Global trends to expand the scope of probiotics use: the relevance of the use of funds based on Bacillus subtilis // Consilium medicum. Gastroenterology. 2012. No. 1. S. 40–44.
    14. Khomeriki N.M., Khomeriki S.G. Some mechanisms of development of side effects of anti-Helicobacter pylori therapy and ways of correction // Consilium medicum.Gastroenterology. 2005.Vol. 7.No. 2.P. 12.
    15. Tsukanov V.V. Clinical and epidemiological aspects of Helicobacter pylori // Experimental and clinical gastroenterology. 2006. No. 1. P. 24–25.
    16. Chicherin I.Yu., Pogorelsky I.P., Darmov I.V. Intestinal microflora: theses about the main thing. M., 2013.21 p.
    17. Chicherin I.Yu., Pogorelsky I.P. and other Transplantation of intestinal microbiota // Journal of Infectology. 2013. No. 2. P. 2–15.
    18. Clostridium difficile: an old bug with new tricks? // DDW Clostridium difficile Symposium.2007. May. 31 p.
    19. Leonard J. Systematic review of the risk of enteric infection in patients taking acid suppression // American Journal of Gastroenterology. 2007. Vol. 102 (9). P. 2047-2056.
    20. Malfertheiner P., Megraud F. et al. Current concept in the management of Helicobacter pylori infection: the Maasticht III – 2000 Consensus report // Gut. 2007. Vol. 56. P. 772–781.
    21. Scaccianoce G., Hassan C. et al. Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10 – day sequential regimen // Can.J. Gastroenterology. 2006. Vol. 20 (2). P. 113-117.
    22. Szajewska H. et al. Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment // Alimentary Pharmacology and Therapeutics. 2010. Vol. 32. P. 1069-1079.
    23. Simren M., Dore J. Gut microbiota for health – current insights and understanding // European Gastroenterology & Hepatology Review. 2012. Vol. 8. P. 3–7.
    24. Vaira D., Zullo A. et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial // Ann Intern Med. 2007. Vol. 146 (8). P. 556-563.
    25. Yang Y., Metz. D. Safety of proton pump inhibitor exposure // Gastroenterology. 2010. Vol. 139. P. 1115-1127.
    26. N.V. Baryshnikova. Clinical and microbiological characteristics of intestinal microbiocenosis and correction of its disorders in patients with chronic gastroduodenitis associated with Helicobacter pylori: Abstract of the thesis.diss. … Cand. honey. sciences. SPb., 2006.24 p.

    .

    Taking N-acetylcysteine ​​with antibiotics to treat Helicobacter pylori infection

    Review Question

    Is the addition of N-acetylcysteine ​​to antibiotics safe and does it improve cure rates of Helicobacter pylori infection?

    Relevance

    Helicobacter pylori ( H pylori ) is a bacterium that lives in the stomach and can cause a number of diseases such as stomach cancer, peptic ulcer disease and others.Colonization occurs in about half of the world’s population and is more common in countries with poor sanitation. People become infected by drinking contaminated water.

    The infection is treated with antibiotics and drugs that reduce stomach acid production. However, antibiotic resistance is on the rise worldwide, reducing cure rates even with medication. New drugs are being tested to improve cure rates. One such drug is N-acetylcysteine ​​(NAC).NAC is a drug that helps dissolve mucus for respiratory problems. NAC can be taken orally or given intravenously. NAC may interfere with some of the survival mechanisms of H pylori and improve cure rates.

    Characteristics of research

    We included 8 studies (randomized controlled trials (RCTs)) with 559 people aged 17 to 76 years. The evidence is current to April 2018. All studies involved outpatients from endoscopy centers (centers that specialize in examination using a flexible tube with a camera inserted into the stomach) in several countries.The combinations of antibiotics tested in the included studies varied widely, as did the doses of NAC (600 to 1,800 mg per day). NAC was compared to placebo (dummy pill) or no treatment.

    Key Outcomes

    We are uncertain whether adding NAC to antibiotics improves cure rates for H. pylori infection compared to adding placebo or not using NAC. Any potential beneficial effect of NAC should be viewed with caution, as the included studies were very different and had a low degree of confidence and deficiencies that could have influenced their results and therefore the results of the review.

    We are not sure if taking NAC is associated with a higher risk of gastrointestinal or allergic adverse events compared to placebo or no NAC. No toxic adverse events were reported in the included studies.

    Large randomized clinical trials with appropriate design, efficacy and safety data collection and reporting of results are needed, especially with regard to recommended antibiotic combinations.

    Quality of evidence

    Overall confidence in the evidence for eradication rates ranged from very low to low.Five studies reported adverse events (side effects), but the confidence in the evidence was very low. The included studies were poorly conducted and this reduced our confidence in the results.

    3.1 Conservative treatment / ConsultantPlus

    – It is recommended to carry out eradication therapy for gastric ulcer and duodenal ulcer associated with H. pylori. [7, 14]

    (Grade of recommendation A; level of evidence 1a)

    – As a first-line therapy, if the resistance to clarithromycin does not exceed 15-20%, it is recommended to use standard triple therapy (according to the latest recommendations of the IV Maastricht Agreement (2010 …), ESPGHAN and NASPGHAN (2011)):

    – PPI (esomeprazolzh vk, rabeprazole, omeprazolzh vk) 1 – 2 mg / kg / day + amoxicillin 50 mg / kg / day + clarithromycin vk 20 mg / kg / day

    – PPI + clarithromycin vk + metronidazolzh vk 20 mg / kg / day.

    Duration of therapy 10 – 14 days.

    (Grade of recommendation A; level of evidence 1a)

    “sequential” regimen, in which PPIs are prescribed for 14 days, and antibiotics are consecutive for 7 days each.

    If the eradication therapy is ineffective, an individual selection of the drug is carried out based on the sensitivity of H. pylori to antibacterial drugs – third-line therapy.

    Standard non-invasive tests are used to assess the effectiveness of anti-Helicobacter pylori therapy. Monitoring the effectiveness of eradication is determined at least after 6 weeks. after the end of treatment.

    – Due to the high level of H. pylori resistance to metronidazole and poor tolerance of tetracycline in children, according to the recommendations of Russian experts, it is recommended to use the following regimens in children:

    – First-line therapy.

    – PPI + amoxicillin vk + clarithromycin vk

    – PPI + amoxicillin vk or clarithromycin vk + nifuratel (30 mg / kg / day)

    – PPI + amoxicillin vk + josamycin vk (50 mg / kg / day, no more 2 g / day).

    It is possible to use a “sequential” scheme.

    – Quadrotherapy is used as a second line therapy:

    – bismuth subcitrate VK + PPI + amoxicillin VK + clarithromycin VK

    – bismuth subcitrate VK + PPI + amoxicillin VK or clarithromycin VK + nifuratel.

    (Grade of recommendation A; level of evidence 1a)

    Comments: Duration of treatment 10-14 days [18].

    – In order to overcome the resistance of H. pylori to clarithromycin and reduce side effects from the use of antibacterial drugs, it is recommended to use a scheme with sequential prescription of antibiotics:

    – PPI + bismuth subcitrate + amoxicillin – 5 days, then PPI + bismuth subcitrate VK + josamycin – 5 days [nineteen].

    (Grade of recommendation A; level of evidence 1a)

    Comments: The low detection rate of familial carriage of HP infection and the lack of a systemic approach to its eradication contributes to the reinfection of HP and, as a consequence, recurrence of duodenal ulcer in children [20].The highest efficacy and safety of anti-Helicobacter pylori therapy is manifested against the background of prebiotic or probiotic therapy.

    – In the case of a peptic ulcer that is not associated with H. pylori, the goal of treatment is to relieve the clinical symptoms of the disease and scar the ulcer. In this regard, the appointment of antisecretory drugs is recommended.

    (Grade of recommendation A; level of evidence 1a)

    – Recommended as drug of choice for peptic ulcer disease not associated with H.pylori, currently use proton pump inhibitors: esomeprazolzh vk, omeprazolzh vk, rabeprazole, which are prescribed at a dose of 1 – 2 mg / kg / day. The duration of the PPI course is 4 weeks for YAD, 8 weeks for DU [21].

    (Grade of recommendation A; level of evidence 1a)

    – h3-blockers have lost their position and are now rarely used, mainly, their appointment can be recommended for peptic ulcer disease not associated with H. pylori, if PPIs are not available (or combinations with them) in order to enhance the antisecretory action [2].

    (Grade of recommendation A; level of evidence 1a)

    – Antacids (aluminum hydroxide or phosphate, magnesium hydroxide) are recommended for use in complex therapy for symptomatic purposes to relieve dyspeptic complaints.

    (Grade of recommendation B; LE: 3)

    Comments: Bismuth subcitrate 8 mg / kg / day is prescribed to enhance cytoprotection for up to 2-4 weeks.

    – In case of disorders of gastrointestinal tract motility, it is recommended to prescribe prokinetics, antispasmodics

    – The effectiveness of treatment for gastric ulcers is recommended to be monitored by the endoscopic method after 8 weeks, with duodenal ulcers – after 4 weeks [21].A general overview of possible treatment regimens is given in Appendix D1. A list of essential medicines used to treat peptic ulcer disease is given in Appendix D2.

    COMPLEX THERAPY FOR HELICOBACTER PYLORI INFECTION IN CHILDREN USING RIFAXIMIN | Niesevich

    1. Scarpignato C. Towards the ideal regimen for Helicobacter pylori eradication: the search continues. Dig. Liver.Dis. 2004; 36: 243-247.

    2. Shcherbakov P.L., Korsunsky A.A., Filin V.A., Tsvetkova L.N. New approaches to the diagnosis and treatment of H. pylori infection in children. Russian Journal of Gastroenterology, Hepatology and Coloproctology. 2001; 11 (appendix 13): 116-118.

    3. Nakayama Y., Graham D. Helicobacter pylori infection: diagnosis and treatment.Expert Rev. Anti – infect. Ther. 2004; 2: 599-610.

    4. Khomeriki N.M., Khomeriki S.G. Some mechanisms of the development of side effects of anti-Helicobacter pylori therapy and ways of their correction. Consilium medicum. 2005; 2 (appendix): 22-25.

    5. Holton J, Vaira D, Menegatti M, Barbara L. The susceptibility of Helicobacter pylori to the rifamycin, rifaximin.J. Antimicrob. Chemother. 1995; 35: 545-549.

    6. Fujimura S., Kato S., Kawamura T., Watanabe A. In vitro activity of rifampicin against Helicobacter pylori isolated from children and adults. J. Antimicrob. Chemother. 2002; 49: 541-543.

    7. Venturini A.P. Pharmacokinetics of L / 105, a new rifamycin, in rats and dogs, after oral administration.Chemotherapy. 1983; 29: 1-3.

    8. Scarpignato C., Pelosini I. Bismuth compounds for eradication of Helicobacter pylori: pharmacology and safety. Progr. Basic. Clin. Pharmacol. 1999; 11: 87-126.

    9. Scarpignato C. Pelosini I. Antisecretory drugs for eradication of Helicobacter pylori: antibacterial activity and synergism with antimicrobial agents.Progr. Basic. Clin. Pharmacol. 1999; 11: 136-180.

    10. Quesada M., Sanfeliu I., Junqvera F. et al. Evaluation of Helicobacter pylori susceptibility to rifaximin. Gastroenterol. Hepatol. 2004; 27: 393-396.

    11. Pretolani S., Bonvicini F., Brocci E. et al. Effect of rifaximin, a new non-absorbed antibiotic, in the treatment of Helicobacter pylori infection.Acta Gastroenterol. Belg. 1993; 56: 144.

    12. Nijevitch A.A., Shcherbakov P.L., Sataev V.U. et al. Helicobacter pylori eradication in childhood after failure of initial treatment: advantage of quadruple therapy with nifuratel to furazolidone. Aliment. Pharmacol. Ther. 2005; 22: 881-887.

    13. Dell’Anna A., Azzarone P., Ferrieri A.A randomized openly comparative study between rifaximin suspension versus rifaximin pills for the eradication of Helicobacter pylori. Eur. Rev. Med. Pharmacol. Sci. 1999; 3: 105-110.

    14. Gasbarrini A., Gasbarrini G., Pelosini I., Scarpignato C. Eradication of Helicobacter pylori: are rifaximin – based regimens effective. Digestion. 2006; 73 (Suppl. 1): 129-135.

    The use of Bacillus clausii reduces the number of side effects in anti-Helicobacter pylori therapy: a randomized, double-blind, placebo-controlled trial

    Introduction

    Therapeutic regimens used for the eradication of Helicobacter pylori , are based on the combined use of antibiotics and proton pump inhibitors (PPIs) [1–8].The outcome of treatment depends on the class of antibiotics used, dose, duration of treatment, bacterial resistance and patient adherence to the prescribed treatment. When carrying out antibiotic therapy, the following side effects from the gastrointestinal tract are noted: diarrhea, nausea, taste disturbances, stomatitis and intestinal distention. These side effects reduce the tolerability of treatment and can lead to its early termination, as well as to failure in the eradication of H . pylori . Insufficient adherence of patients to the prescribed treatment is another reason for the failure to eradicate H . pylori . Although the number of patients dropping out of clinical trials is relatively small, the situation may be very different in clinical practice.

    Probiotics are drugs containing microbial cells or components of microbial cells that can have a beneficial effect on the human body [9].Recently, it was suggested that the use of probiotics can increase the tolerability of treatment due to a decrease in the number of side effects that accompany the use of various anti-Helicobacter eradication therapy regimens [10–12].

    For probiotic strains previously used in eradication studies H . pylori, include Lactobacillus GG, Saccharomyces boulardii or combinations of different strains. According to the data of these studies, the addition of probiotics increased the tolerance of eradication therapeutic regimens and, at the same time, did not have a significant effect on patient adherence to the prescribed treatment [9-11].

    Bacillus clausii is a probiotic that has been widely used in Italy since the 1960s for viral diarrhea in children, as well as for side effects caused by antibiotic therapy [13]. Disputes B . clausii are able to survive in the acidic environment of the stomach, activate and reach the intestines, where they develop into vegetative forms [14, 15]. Experimental data indicate that both spores and cells B . clausii can attach to the intestinal wall and colonize its mucosa [16].

    The aim of our double-blind, randomized, placebo-controlled study was to evaluate the effect of oral bacteriotherapy using B . clausii for side effects from the gastrointestinal tract that occur during anti-Helicobacter pylori therapy.

    Methods

    Patients

    This study was a single-center, double-blind, prospective, randomized, placebo-controlled study.It was carried out in a day hospital for patients with a therapeutic profile, including those suffering from diseases of the gastrointestinal tract (Gastroenterology and Internal Medicine Day Hospital), Gemelli Hospital, Rome, Italy. From November 2001 to June 2002, one hundred twenty H. pylori – positive patients who did not have gastrointestinal symptoms (wives or relatives of patients suffering from gastrointestinal diseases caused by H.pylori , who asked for a H. pylori test and subsequent treatment).

    Eligible for inclusion in the study were persons aged 18 to 65 years who had not had gastrointestinal symptoms in the last 3 months, who had H. pylori infection, as evidenced by the results of 13 C-urease breath test. Exclusion criteria were: recent (less than 3 months ago) use of antimicrobial drugs, bismuth compounds, proton pump inhibitors, H 2 receptor inhibitors, laxatives, antidiarrheal drugs, other probiotics, alcohol or illegal drug abuse.The study also did not include patients with acute and chronic gastrointestinal diseases, severe concomitant diseases, including mental disorders, pregnant and lactating women. Patients with long-term drug use were considered eligible for the study if they received the drug for> 3 months. All patients gave their written informed consent to participate in the study.

    Treatment

    Using permutation block randomization (1: 1), 120 patients were assigned to the following parallel groups:

    – sixty patients (male / female – 33/27, mean age 46.2 ± 12.83 years) were randomized to receive a three-way therapy based on the use of clarithromycin 500 mg twice a day, amoxicillin 1 g twice a day, rabeprazole 20 mg twice a day for 7 days and a probiotic preparation – one bottle three times a day (each bottle contains 2 ´ 10 9 spores B . clausii, Enterogermina, non-prescription drug manufactured by Sanofi-Synthelabo, Milan, Italy) for 14 days during eradication therapy and then for 1 week after its completion;

    – sixty patients (men / women – 25/35, mean age 43.1 ± 13.36 years) were randomized to receive placebo (one bottle of placebo preparation three times a day for 7 days of eradication therapy and then for 1 week after its completion). The placebo preparation was identical in color, size, shape, weight and taste to the probiotic preparation.

    Side effects

    Each patient was asked to keep a special validated diary every day for 4 weeks starting from the first day of eradication therapy [11]. The diary contains a questionnaire (a slightly modified questionnaire by DeBoer et al.) [17], which is used to assess the time of onset, the severity and frequency of occurrence of side effects from the gastrointestinal tract: epigastric pain, bloating, diarrhea, constipation and skin rashes.The severity of symptoms was assessed on a scale in which 0, 1, 2 and 3, respectively, meant no symptoms, mild, moderate and severe symptoms. The general assessment of the tolerability of the treatment was made by the patient himself at the end of the first and second weeks of treatment. Tolerability of the treatment was assessed on a scale in which 1, 2, 3, 4 and 5, respectively, meant: 1 – no side effects were observed; 2 – mild side effects that do not affect the daily activity of the patient; 3 – moderate side effects that have little effect on the patient’s daily activity; 4 – severe side effects that affect the daily activity of the patient, but do not require discontinuation of treatment; 5 – severe side effects requiring discontinuation of treatment.Treatment adherence was assessed by counting the number of vials returned by the patient (patients who returned <80% empty vials were not included in the "Compliant Population" (PP) statistically).

    Helicobacter pylori eradication

    Eradication of Helicobacter pylori was assessed by the 13 C-urease breath test performed 6 weeks after completion of treatment.The delta value 90 260 13 90 261 C, which was 3.5 times higher than the initial value, indicated the presence of active Helicobacter pylori infection.

    Statistical analysis

    Statistical analyzes evaluated the following patient populations:

    – “Safety population” – all randomized patients who received at least one dose of the study drug;

    – “Intention-to-treat population (ITT)” – all randomized patients who received at least one dose of the study drug, completed and returned the first diary, which contained the assessment of at least one symptom, per during the course of 7-day eradication therapy.Missing data arising in connection with early termination of treatment in the analysis of the frequency of occurrence of symptoms were regarded as treatment failure, and in the analysis of the severity and frequency of symptoms were replaced by the average value of the available daily patient ratings, expressed in points;

    – “Per protocol population” – all randomized patients who completed the study without violating the protocol.

    Descriptive analysis of demographic, history and clinical data for each of the treatment groups was carried out.When analyzing dichotomous variables, the criterion χ 2 was used, and the relative risk index (RR) and its 95% confidence interval (CI) were calculated. Differences between the two groups in terms of severity of symptoms, summarized as a total time mean, were assessed by ANOVA after rank transformation of the cumulative value for the treatment group, the mean values ​​reported in the patient’s diary, and the dependence of the treatment effect on time.To determine the overall tolerability of therapy, the distribution of patients with side effects in two treatment groups was analyzed using the Kruskal-Wallis test. The criteria were two-sided and a P-value <0.05 was considered statistically significant.

    Calculation of the sample size

    Based on a previous study [9], it was calculated that at a study power of 80% and a 5% two-tailed level of significance, a sample of 120 was sufficient to detect ≥20% difference between groups in terms of nausea, diarrhea, and taste disturbances.

    Results

    Baseline indicators. The main indicators of the study participants are shown in table. 1.

    There were no significant differences in terms of patient age and baseline symptom scores (all patients were asymptomatic at the time of enrollment) between the placebo group and the group receiving B. clausii . Clausii group showed a predominance of males, and in the placebo group, females.

    Research progress . Six patients (three in the B. clausii group and three in the placebo group) did not start the prescribed treatment. Eight patients (four in the B. clausii group and four in the placebo group) did not return the first diary. Another six patients (four in the B.clausii group and two in the placebo group) were not included in the “according to protocol” analysis due to the fact that they either did not return the second diary, were withdrawn from the study or did not comply dosing regimen (i.e. <80% of vials returned) (Fig.one).

    Clausii and placebo group eradication rates H. pylori were similar. In particular, the results of the ITT analysis demonstrated that the eradication of H. pylori was achieved in 39 of 54 patients (72.2%) in the B. clausii group and in 37 of 52 patients (71.15%) in the placebo. In the “population by protocol” (PP), H. pylori eradication was achieved in 39 of 50 patients (78%) in the B group.clausii and 37 out of 50 patients (74%) in the placebo group.

    Influence of Bacillus clausii on the incidence and severity of side effects . ITT and PP analyzes showed significant differences between the two treatment groups in terms of the incidence of nausea, diarrhea and epigastric pain. According to ITT analysis, the RR of nausea in patients receiving B. clausii decreased by half compared with patients in the placebo group after 1 (RR = 0.5; 95% CI 0.31-0.88) and 2 weeks (RR = 0.45; 95% CI 0.21–0.96) of bacteriotherapy.Clausii group also showed a significant reduction in the risk of diarrhea compared with placebo after 1 (RR = 0.30; 95% CI 0.12-0.76) and 2 weeks (RR = 0.38; 95 % CI 0.08-1.9). With regard to pain in the epigastric region, after 1 week the relative risk was 0.68; 95% CI 0.48–0.97 (Table 2). The incidence of vomiting, constipation and skin rash in the B. clausii group was also lower than in the placebo group, although this difference was not statistically significant.The average severity and frequency of nausea and diarrhea in the B. clausii group were also significantly lower (Table 3). In the ITT population, the individual patient’s own assessment of the overall tolerability of treatment in the group receiving B. clausii was significantly higher than in the group receiving placebo. This difference was statistically significant after the 2nd week of treatment (P <0.05) (Table 4).

    Discussion

    The results of this study indicate that patients treated with B.clausii during anti-Helicobacter eradication therapy, there were significantly fewer side effects compared to those patients who received placebo in addition to the therapeutic regimen. These side effects include diarrhea, nausea, and epigastric pain.

    This difference was more pronounced during the first week of treatment when antibiotics were used and the incidence of side effects was higher in both groups. Application B . clausii influenced the incidence of nausea, diarrhea and epigastric pain, especially the severity and frequency of diarrhea. These characteristics were significantly lower in the probiotic group compared to the placebo group. In previous studies [9, 11], oral administration of probiotics during anti-Helicobacter pylori therapy (PPI, clarithromycin, tinidazole) led to a decrease in the incidence of diarrhea, nausea and taste disturbances.In accordance with the recommendations of the Maastricht Agreement-2 (2000) [6], in this study, for the first time, amoxicillin was used instead of tinidazole. The lower incidence of taste disturbances observed in our study can be explained by the change in antibiotic, since taste disturbances are one of the most common side effects associated with the use of tinidazole and other drugs of the nitroimidazole group. Side effects caused by the use of antibiotics are quite common and occur mainly from the gastrointestinal tract.The intestinal environment is characterized by a significant accumulation of bacteria – up to 10 12 –10 14 CFU / ml in the colon. These bacteria coexist in a certain equilibrium with the cells of the mucous membrane of the large intestine. Antibiotic therapy can disturb this balance and lead to the dominance of opportunistic flora over the normal obligate microflora.

    A change in the composition of the bacterial microflora of the intestine can be triggered by any antibiotic, however, the drugs that most often cause such side effects are broad-spectrum antibiotics (for example, tetracyclines, aminoglycosides, macrolides and penicillins).Moreover, macrolide antibiotics such as clarithromycin can increase gastrointestinal smooth muscle contractility, which can lead to increased intestinal motility, increased intestinal transit, and diarrhea.

    Probiotics can also cause changes in the intestinal flora. Probiotics most often include such types of microorganisms as spore-forming bacteria, lactobacilli and yeast. The use of probiotics has been proven to be beneficial and effective in a variety of gastrointestinal diseases such as antibiotic-associated diarrhea [19] and inflammatory bowel disease [20].Similar effects of probiotics in human diseases are explained by the synthesis of substances with antimicrobial properties, competition with pathogenic microorganisms for nutrients and sites of microbial adhesion, modification of toxins or toxin receptors, incomplete absorption of lactose, and changes in the immune system [21].

    Application B . clausii as a probiotic microorganism based on more than 40 years of clinical experience in Italy; at the same time, its excellent tolerance and the absence of side effects were noted.Moreover, it has some unique properties: it is resistant to the most commonly prescribed antibiotics [22], is not part of the normal obligate intestinal microflora, and has sporogenic activity [13, 23–25]. Spores Bacillus clausii can survive in the acidic environment of the stomach, activate and reach the intestine, where they develop into vegetative forms [14, 15]. However, the very mechanism of action of spores B . clausii in the process of restoration of intestinal microflora has not yet been fully studied.Experimental data indicate that both spores and cells B . clausii can attach to the intestinal wall and colonize its mucous membrane [16]. The results of previous studies have demonstrated the positive effect of probiotics in rotavirus diarrhea, as well as in children with side effects from the gastrointestinal tract caused by the use of antibiotics [13]. However, this study had several limitations. First, the occurrence of side effects during anti-Helicobacter pylori therapy was mainly associated with the use of medium or high doses of antibiotics or the combined use of several antibiotics.While some side effects, such as diarrhea, can be attributed to antibiotic-induced disturbances in the intestinal microflora, the relationship between the composition of the intestinal microflora and other side effects, such as nausea and epigastric pain, has not yet been proven. Until the mechanisms of action of probiotics are fully understood, caution should be exercised in arguing that clinical improvements are due to oral administration of probiotics. Secondly, we did not conduct a study of feces for the composition of bacterial microflora.However, previous studies on the composition of fecal microflora confirmed the presence of B. clausii in feces after oral administration of commercially available drugs. It has also been proven that B . clausii is resistant to the antibiotics used in this study. And third, the results obtained in our study apply only to individuals who received antibiotic therapy who did not have gastrointestinal symptoms.In fact, we included asymptomatic patients who wanted to eradicate their Helicobacter pylori infection in the study in order to assess the new side effects associated with the therapy. The inclusion of asymptomatic patients made it possible to more clearly determine what effect the additional inclusion of a probiotic in the treatment regimen has on the incidence of side effects, but also limited the extent of this effect on the severity of symptoms, since the baseline scores, expressed in points, were close to zero.

    We believe that in patients with dyspepsia, the addition of B. clausii to the treatment regimen will reduce the number of side effects to a level that will be of significant clinical importance, however, it should be recognized that data to support this theory have not yet been obtained. Therefore, additional clinical studies will be required to confirm this point of view.

    It should be noted that any difference between the two groups regarding the level of eradication of H.pylori was not observed. This result, which is fully consistent with the data of previous studies on the study of living probiotic microorganisms [9, 11], suggests that B . clausii in the form and concentration in which it was used during our study does not have antibacterial activity against H. pylori . Although not particularly significant, slightly lower rates of eradication of infection were obtained in both treatment groups using the same antibiotic regimens as in previous studies [26].This result was somewhat unexpected and could partly be explained by the higher antibiotic resistance characteristic of our geographic area. The reported rate of clarithromycin resistance in Italy is about 10% [27]. As in previous studies [9, 11], the use of B . clausii had no effect on the overall level of patient adherence to the prescribed treatment. However, the sample size was calculated in such a way as to reveal a difference in the incidence of adverse events, and not in the level of eradication or general adherence of patients to the prescribed treatment.Moreover, the patients included in the study themselves requested eradication therapy. Thus, they probably had a special motivation to complete the full course of treatment, despite the side effects that arose. Although the additional inclusion of B. clausii in the therapeutic regimen does not affect the level of eradication and the general adherence of patients to the prescribed treatment, it has a definite advantage, reducing the number of side effects. On a case-by-case basis, the physician must decide whether to additionally include B . clausii into the patient’s treatment regimen in order to prevent mild and moderate side effects without affecting the patient’s adherence to the prescribed treatment. You should also take into account the cost of the drug and the individual preferences of the patient.

    In conclusion, we note that in this study, it was demonstrated that when using B. clausii during and after standard seven-day anti-Helicobacter pylori therapy, patients had a lower incidence of side effects, as well as a much better tolerance to combination antibiotic therapy compared with placebo.

    Helicobacter pylori bacterium: means, drugs and medicines

    The reasons for the development of stomach and duodenal ulcers have long remained a mystery to scientists. But in 1979, the main suspect was discovered – the bacterium Helicobacter pylori, which lives in the gastrointestinal tract. It can exist there for a long time without causing harm to health, but under favorable – for the bacteria – circumstances, it begins to actively multiply and damage the mucous membranes.

    Helicobacter pylori bacterium – a dangerous enemy of the gastrointestinal tract

    A widespread and dangerous microorganism – the bacterium Helicobacter pylori, which in most cases causes stomach and duodenal ulcers. She is not afraid of the hydrochloric acid contained in the gastric juice. The bacterium can live for years in this environment and destroy the mucous membranes, provoking the development of gastritis, gastroduodenitis, gastric ulcer and duodenal ulcer.With a neglected ulcer, the development of oncology is also possible.

    Helicobacter pylori infection usually occurs by contact, most often through saliva. However, you can also get an infection with contaminated food or water. Infection with this bacterium by airborne droplets is impossible. Since Helicobacter pylori is transmitted mainly through the contact-household route, doctors call it a “family” microbe: if one of the household members has this bacterium, then it is likely that the rest also have it – the probability of this is 95%.

    According to some data, the number of infected people reaches 60%, but not in every case antibiotic therapy is really necessary. Most often, the concentration of bacteria is small and cannot be harmful to health. Our immune system keeps the number of bacteria under control, but sometimes the defense is weakened – this can lead to physical and nervous strain, infectious diseases, bad habits and an unhealthy lifestyle. Then Helicobacter pylori is activated and begins to multiply intensively.This happens in about 15% of all cases of H. pylori infection. Unhealthy food can also weaken the defense – sour or spicy foods, pickles and smoked meats that irritate the stomach lining, giving bacteria access. A violation of the diet can lead to the same outcome – contrary to the recommendations of doctors who advise to eat often and a little, most of the townspeople eat, at best, twice a day or are interrupted by fast food: pastries, snacks and various other dry food.

    As a rule, at the initial stage, gastritis develops, then an ulcer, and without proper treatment, you need to be prepared for extremely serious consequences – perforation of an ulcer, bleeding and the occurrence of oncological pathology.In addition, in this case, certain structural changes are possible not only in the gastrointestinal tract, but also in the liver and pancreas.

    Fun Fact
    In the 1970s, it was believed that gastritis and stomach ulcers caused stress and an unbalanced diet. One of the pioneers of Helicobacter pylori, Australian scientist Barry Marshall, was sure that it was this bacterium, and not chips with soda, that provoke pathologies. To prove his point, he, being completely healthy, drank a concentrate of the culture of Helicobacter pylori.Within a few days he developed signs of gastritis. The suffering was not in vain – Marshall and his colleagues received the Nobel Prize in 2005 for their scientific work on Helicobacter pylori.

    In case of gastritis, gastroduodenitis and peptic ulcer disease, the doctor will definitely refer you for tests. The purpose of the research is to find the culprit, that is, the bacterium Helicobacter pylori, and also to assess the damage caused by the infection. To do this, they do a general and biochemical blood test, an analysis of gastric juice, a biopsy, as well as a high-precision PCR analysis, which allows you to find Helicobacter pylori DNA even if its concentration is low.

    Medicines for infections caused by the bacterium Helicobacter

    Over the past 30 years, several effective methods for the destruction of Helicobacter pylori have been developed. In 2005, a worldwide consensus of gastroenterologists took place in the Netherlands, on which protocols for the treatment of diseases provoked by Helicobacter pylori were developed and approved. These regimens have a positive effect in 80% of cases, and the incidence of side effects does not exceed 15%.

    Treatment usually takes 14 days and is drug-based.However, for the therapy to be effective, it is also necessary to change the lifestyle and adhere to a specific diet.

    Tips
    Many skin problems – acne, atopic dermatitis, psoriasis – can be associated with the activity of Helicobacter pylori. Scientists do not yet have absolutely accurate data, but it is already obvious that these pathologies are more common in infected Helicobacter pylori.

    How to eliminate Helicobacter pylori bacteria? The treatment consists of three stages.The first line of drugs to fight this bacterium often works as expected, but if it is not effective enough, doctors will prescribe a second line of drugs. If the second line did not cope with the bacteria, then the third line means are used.

    First-line eradication drugs

    This treatment regimen is called a three-drug regimen because it uses a combination of three drugs. It consists of the antibiotics clarithromycin and amoxicillin, which kill bacteria, and proton pump inhibitors (the active ingredient is omeprazole, etc.)- drugs that regulate acidity. Thanks to the use of proton pump inhibitors, the patient gets rid of many manifestations of gastritis and peptic ulcer disease, in addition, he can adhere to a less strict diet during treatment – although, of course, the diet should still be healthy and balanced. In some cases, drugs based on amoxicillin are changed to another antibacterial agent – metronidazole or nifuratel.

    Sometimes the doctor can add a fourth component – bismuth preparations, which have a gastroprotective, anti-inflammatory and astringent effect, but usually such agents are prescribed in the second stage.Nevertheless, these drugs have a positive effect on the course of the disease: they form a kind of film on the inner walls of the stomach, thereby dulling the pain syndrome and relieving the inflammatory process.

    For elderly patients, a milder regimen is used, which includes only one antibiotic (amoxicillin), bismuth preparations and proton pump inhibitors.

    The standard duration of the first stage is one week. In case of insufficient effectiveness, the course can be extended up to 2 weeks, but no more.For about 90–95% of patients, such therapy is effective and the second stage is not required at all. However, if by the end of the first stage not all bacteria have died, the treatment regimen needs to be changed.

    Second-line eradication drugs

    The second-stage treatment regimen is called a four-component regimen. It includes one proton pump inhibitor, a bismuth drug and two antibiotics that mutually reinforce each other. As a rule, drugs with the active ingredients tetracycline and metronidazole are used, if they were not used at the first stage.Usually, antibiotics are chosen that have not yet been used in treatment, since if the H. pylori bacterium survived the first exposure to certain antibacterial agents, then it is obvious that this strain is insensitive to them.

    The second version of this therapy consists of drugs based on amoxicillin, an antibiotic from the nitrofuran group, a proton pump inhibitor and a bismuth drug. At this stage, they are very often included in the treatment regimen.

    Means with tripotassium dicitrate of bismuth have a bactericidal effect, stimulate cytoprotective mechanisms, increase the resistance of the mucous membrane to harmful influences.The drugs restore the protective functions of the stomach and can prevent relapses of the disease.

    In order not to reduce the effectiveness of the active substance, it is recommended to stop eating fruits, juices and milk while taking bismuth-based products.

    The duration of therapy is 10 to 14 days.

    Third-line eradication drugs

    In very rare cases, a positive effect cannot be achieved even after using second-line drugs.Then tests are carried out that determine the sensitivity of bacteria to various types of antibiotics, and the most effective antibacterial drugs are included in the scheme. In general, this stage differs little from the second – proton pump inhibitors, bismuth preparations and two antibiotics are prescribed, which showed the greatest efficiency during laboratory studies.

    Bismuth medicines also play an important role at this stage, as they provide a comprehensive treatment. Preparations with the active ingredient bismuth tripotassium dicitrate not only effectively relieve unpleasant symptoms of the disease (heartburn, pain, bloating), but also have a local bactericidal effect against Helicobacter pylori, help to activate the regeneration of damaged cells of the stomach walls.Therefore, the role of such agents in the effective treatment and destruction of the Helicobacter pylori bacteria can hardly be overestimated.

    It should be noted that the bacterium Helicobacter pylori is not always the cause of ulcers; constant irritation of the gastric mucosa with certain medications (for example, drugs with the active ingredients acetylsalicylic acid and ibuprofen, which are often taken without a doctor’s recommendation) can also lead to it. Stomach trauma and certain chronic diseases (diabetes, hepatitis, tuberculosis) can also lead to similar changes.But in 75% of cases, ulcers and gastritis are the “handiwork” of Helicobacter pylori. To protect yourself from infection, you must strictly follow the rules of personal hygiene – do not eat unwashed fruits and vegetables, do not share dishes with anyone, wash your hands before eating, and do not eat anything from other people’s plates. However, infection is still likely – one kiss is enough to transmit the infection.

    Don’t give harmful bacteria a chance. If you are not sure if you are infected, have a laboratory test, such as a PCR test for H. pylori.Even if the bacteria is found, this does not mean that you need treatment. Helicobacter is not always the cause of gastritis, but it is present in everyone’s body. As stated above, a healthy immune system can control the concentration of this bacterium. To prevent the development of diseases associated with Helicobacter, you need to adhere to a healthy diet that excludes everything that can irritate the stomach lining – marinades, spices and hot seasonings, fried, alcohol, coffee and carbonated drinks, sour vegetables and fruits.But if, nevertheless, gastritis is diagnosed, regardless of the cause of its occurrence, it is imperative to protect the stomach, and bismuth preparations, which have a gastroprotective, anti-inflammatory and astringent effect, do the best with this.

    pass the examination and find out your result at the MEDSI clinic in St. Petersburg

    Table of Contents

    Urease breath test is one of the highly effective methods for diagnosing gastric contamination with Helicobacter pilori bacteria.The method is based on the ability of Helicobacter to release the urease enzyme, which converts the introduced reagent carbamide (0.5 g) into ammonia released with the breathing air. The urease activity of the bacteria is read by analyzing the exhaled air with a digital apparatus.

    Breathing tests for Helicobacter pylori are absolutely painless, non-invasive and informative methods for detecting Helicobacter pyloriosis. They require minimal preparation of the patient and the urease breath test has no contraindications.

    Indications for the appointment of breath tests for Helicobacter pylori

    A gastroenterologist or family doctor, general practitioner, pediatrician or other doctor may order Helicobacter breath tests for the following conditions or diseases:

    • The onset of heaviness, discomfort or pain in the stomach during or after eating, aching, stabbing, pressing or cramping
    • Frequent belching
    • Heartburn
    • Decreased appetite
    • Bad breath
    • Onset of nausea or vomiting after eating
    • Gastritis, gastroduodenitis, peptic ulcer or other previously identified acid-related diseases of the digestive system
    • Presence of unexplained iron deficiency anemia, idiopathic thromocytopenic purpura, vitamin B12 deficiency
    • Before prescribing aspirin and NSAIDs to reduce the risk of erosive and ulcerative lesions of the stomach and duodenum and bleeding from the upper gastrointestinal tract in patients infected with H.pylori
    • In patients with a history of gastric cancer heredity
    • Helicoter pylori
    • was detected in one of the family members during the tests

    • Failure to perform or contraindications to performing FGDS
    • The need to evaluate the effectiveness of the conducted eradication therapy

    When preparing for breath tests for Helicobacter pylori, the patient must observe the following rules:

    • The examination is carried out in the morning on an empty stomach: before the examination, exclude food and water intake.The last meal should be “light” with the exception of meat, fish, mushrooms and at least 12 hours before the study
    • The test should only be administered 4-6 weeks after taking antibiotics or antisecretory drugs. Taking analgesics, anti-inflammatory or antacid drugs, bismuth drugs should be discontinued 14 days before the study. It is imperative to inform the doctor about the use of other drugs for possible correction of drug intake
    • You can not take strong alcoholic drinks for 3 days before the examination
    • You cannot eat legumes (beans, peas, lentils, soybeans) for 3 days before the examination
    • Do not eat or chew gum on the morning of the study.You should quit smoking 3-4 hours before the procedure
    • Before the test, brush your teeth and rinse your mouth thoroughly. After that, do not use mouth rinses, etc.

    How the study is conducted

    To pass the helik test, you should do the following:

    • The patient is comfortable in a sitting position
    • Before examination, rinse mouth thoroughly with water
    • The doctor prompts the patient to breathe normally into the plastic tube for 6 minutes.Breathing should not be forced, and the tube used should not touch the tongue or palate. If saliva enters the tube, the study should be restarted
    • The results of the background examination are read and stored automatically
    • After that, the doctor gives the patient 0.5 g of urea, which is previously dissolved in 50 ml of water
    • Next, the patient rinses his mouth with water again and breathes into the tube from the other side. This analysis step also takes 6 minutes
    • After the completion of the second part of the examination, the results are recorded again and their automatic processing is carried out

    Results

    Data processing and drawing up an opinion is carried out automatically and is issued in the form of a report on the survey performed, indicating the presence or absence of Helicobacter pylori infection.