Newer Agents And Nontraditional Therapies For H Pylori Eradication: Hope Is Coming
In the last decade, many researchers have argued that new classes of antimicrobials with novel mechanisms of action are necessary to overcome increasing drug resistance. Some agents have shown an antibacterial effect against H. pylori in vitro regardless of drug resistance and are effective even at low pH. Among them, pyloricidin A, B, and C have a strong and selective anti-H. pylori effect which an MIC90 value of 0.013 mg/L. Benzimidazole derivatives , polycyclic compound , arylthiazole derivative 44 also were highly effective against H. pylori.
Cathelicidins and defensins are examples of human antimicrobial peptides native to the innate immune system of many eukaryotes that have activity against H. pylori. LL-37 is a cathelicidin with an anti-H. pylori effect, and a recent study demonstrated that cathelicidin limited H. pylori colonization and related gastritis in mouse models. Defensin peptides have also been indicated to impede H. pylori. Human beta defensin 2 and 3 are differentially expressed in gastric mucosa during H. pylori infection. Oligo-acyl-lysyl peptides, which have a structure and function similar to those of natural AMPs, have broad-spectrum antibacterial activity and anti-H. pylori effect in vivo. Unlike the natural AMPs, OAK peptides are without known proteolytic cleavage sites and thus, resistant to enzymatic cleavage.
What Causes H Pylori
Its not known exactly how the bacterium is spread, but it has co-existed with humans for thousands of years. It can be transmitted person to person via saliva or stool, or it can hitch a ride to your stomach via undercooked food, especially chicken. Contaminated water is also a risk factor. Poor hygiene is a risk factor, making the bacterium more prevalent in underdeveloped areas.
You can prevent H pylori with good hygiene, like hand washing, but its important to note that if your digestive system is in good working order, you may be able to successfully ward off the bacteria if you come in contact with it. This is true of any parasite or pathogenic bacterial infection. The hydrochloric acid produced in the stomach should have a pH of about 2, acidic enough to break down food AND kill invaders. If your immune system and digestive tract are working well, you wont become infected even if you come in contact with these invaders because you should be able to kill them before they take root and proliferate. Many of us have inadequate HCl production, making us more susceptible to pathogens and parasites. HCl production declines with age, which may be one reason why older people have a higher rate of H pylori infection.
Sequential Therapy: Between First And Second Line
The primary goal of the sequential regimen is to overcome clarithromycin resistance. Several studies have shown that a novel 10-day sequential therapy can achieve success rates of 90%94%.33,34 The regimen consists of a 5-day dual therapy with a PPI and amoxicillin , followed by a 5-day triple therapy with a PPI , clarithromycin , and metronidazole . One study from Thailand reported a 95% eradication rate for a 10-day sequential therapy,35 while a study from Turkey, where eradication rates are low, showed 78% eradication for sequential therapy versus 53% for standard triple therapy based on a per-protocol analysis.36 In China, a comparative study showed eradication rates of 83% for bismuth-based quadruple therapy and 81% for standard triple therapy, with an eradication rate of 89% for sequential therapy.37
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What Are The Indications For H Pylori Testing And Treatment
Testing for H. pylori is indicated in certain patients. Any patient who tests positive for H. pylori infection should be treated.
All patients with active or previous peptic ulcer disease should be tested for H. pylori infection unless there is documentation that the infection was previously cured. Patients with low-grade gastric mucosaassociated lymphoid tissue lymphoma or a history of endoscopic resection of early gastric cancer should also be tested. Testing in patients with gastroesophageal reflux disease is not recommended unless the patient has a history of peptic ulcer disease or dyspepsia. If a patient with gastroesophageal reflux disease is tested and found to have H. pylori infection, treatment should be offered with the acknowledgment that symptoms of gastroesophageal reflux disease are unlikely to improve.
Based on low-quality evidence, the ACG also recommends testing for those initiating long-term nonsteroidal anti-inflammatory drug therapy, those with unexplained iron deficiency anemia, and adults with idiopathic thrombocytopenic purpura.
There is insufficient evidence to make a recommendation about testing and treatment in asymptomatic patients with a family history of gastric cancer or in patients with lymphocytic gastritis, hyperplastic gastric polyps, or hyperemesis gravidarum.
How Do Doctors Treat An Nsaid
If NSAIDs are causing your peptic ulcer and you dont have an H. pylori infection, your doctor may tell you to
- stop taking the NSAID
- reduce how much of the NSAID you take
- switch to another medicine that wont cause a peptic ulcer
Your doctor may also prescribe medicines to reduce stomach acid and coat and protect your peptic ulcer. Proton pump inhibitors , histamine receptor blockers, and protectants can help relieve pain and help your ulcer heal.
Ideal Length Of Treatment For Helicobacter Pylori Eradication
The ideal duration of therapy for H. pylori eradication is controversial, with recommendations ranging from 7 to 14 days. A proton pump inhibitor plus two antibiotics is the most commonly used first treatment to remove H. pylori infection. Current data suggest that increasing the length of treatment to 14 days of a PPI plus amoxicillin and clarithromycin or amoxicillin and a nitroimidazole significantly increases the eradication rate, while increasing the adverse events by a small amount. Based on the overall evidence, the ideal length of treatment with a PPI plus amoxicillin and clarithromycin is at least 14 days.
Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.
The primary objective was to assess the relative effectiveness of different durations of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events.
Helicobacter Pylori Eradication Protocols
Helicobacter pylori eradication protocols is a standard name for all treatment protocols for peptic ulcers and gastritis in the presence of Helicobacter pyloriinfection. The primary goal is not only temporary relief of symptoms but also total elimination of H. pyloriinfection. Patients with active duodenal or gastric ulcers and those with a prior ulcer history should be tested for H. pylori. Appropriate therapy should be given for eradication. Patients with MALT lymphoma should also be tested and treated for H. pylori since eradication of this infection can induce remission in many patients when the tumor is limited to the stomach. Several consensus conferences, including the Maastricht Consensus Report, recommend testing and treating several other groups of patients but there is limited evidence of benefit. This includes patients diagnosed with gastric adenocarcinoma , patients found to have atrophic gastritis or intestinal metaplasia, as well as first-degree relatives of patients with gastric adenocarcinoma since the relatives themselves are at increased risk of gastric cancer partly due to the intrafamilial transmission of H. pylori. To date, it remains controversial whether to test and treat all patients with functional dyspepsia, gastroesophageal reflux disease, or other non-GI disorders as well as asymptomatic individuals.
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How To Eradicate H Pylori
Helicobacter pylori is a hardy spiral shaped bacterium which multiplies and colonizes in the stomach. H. pylori can survive gastric acids due to its ability to produce an enzyme called urease. Urease neutralizes stomach acid, making it easy for the bacteria to survive in it own acide-free zone.
H. Pylori is the only bacterial organism that can survive in the hydrochloric acid in the stomach.
The bacteria can easily penetrate the stomachs protective mucous lining. It can even trick the stomach into making more stomach acid which makes the stomach lining more susceptible to damage through exposure to acid and pepsin. This can cause stomach ulcers.
Efficacy Of Pam According To Metronidazole Susceptibility
Primary metronidazole resistance was reported in 26 studies.,,,,,,,,,,,,,,,,,,,,,,,,, It was present in 665 out of 2092 patients tested . Twenty-two studies,,,,,,,,,,,,,,,,,,,,, including 1874 patients reported the efficacy of PAM according to metronidazole susceptibility. H. pylori was cured in 348 of 588 patients harbouring metronidazole-resistant strains versus 1145 of 1286 in metronidazole-susceptible strains . The risk difference was 0.30 .
The subanalyses showed that the decrease in the efficacy of treatment in resistant strains was 39% when the treatment was administered for 7 days, compared with 14% when it was administered for 10 days and 21% when administered for 14 days .
Risk difference of the efficacy of PAM in metronidazole-susceptible strains versus metronidazole-resistant strains subanalyses according to drug schedule and treatment duration
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Clinical Characteristics Of Pud
Patients suffering from peptic ulcer disease typically complain about burning epigastric pain , which may or may not radiate toward the back. In people with stomach ulcers, the pain intensifies with meals while, on the other hand, people suffering from duodenal ulcers feel pain relief after they eat.
Additional symptoms of peptic ulcer disease include nausea and vomiting, a loss of or increase in appetite, and consequent weight loss or gain. The frequent occurrence of dyspepsia , belching, bloating and stomach distension are reported as well. And finally, complications such as bleeding develop in a form of hematemesis and melena. While examining the patient and palpating his or her abdomen doctor can confirm epigastric tenderness.
Helicobacter Pylori Triple Therapy
Helicobacter pylori: triple therapy :
- offer people who test positive for H pylori a 7-day, twice-daily course of treatment with:
- a PPI and
- amoxicillin 1g and
- either clarithromycin 500mg or metronidazole 400mg
Second-line treatment in adults
- offer people who still have symptoms after first-line eradication treatment a 7-day, twice-daily course of treatment with:
- a PPI and
- amoxicillin 1g bd and
- either clarithromycin 500mg bd or metronidazole 400mg bd
Seek advice from a gastroenterologist if eradication of H pylori is not successful with second-line treatment
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Indications For The Treatment Of H Pylori Infection
H pyloriHelicobacter pyloriGut.Gastroenterology.Am J Gastroenterol.Helicobacter pyloriGut.
|Following resection of a gastric cancer
|First-degree relatives of patients with gastric cancer
|Unexplained iron-deficiency anemia
|Before commencing NSAID therapy in NSAID-naïve patients
|Patients receiving long-term aspirin therapy who develop gastrointestinal bleeding
Search Strategy For Identification Of Studies
Trials were identified by searching the Cochrane Controlled Trials Register, PubMed , Embase , andthe Science Citation Index . A search strategy wasconstructed using a combination of the following words: Helicobacterpylori or H. pylori and moxifloxacin or avelox.Only articles published in English were included. Reference lists from thetrials selected by electronic searching were manually searched to identifyfurther relevant trials. We also conducted a manual search of abstracts from1995 to 2012 from the following congresses: International Workshop ofthe European Helicobacter Study Group, American Digestive Disease Week, andUnited European Gastroenterology Week. Abstracts of the articles selected ineach of these multiple searches were reviewed, and those meeting the inclusioncriteria were recorded. References of reviews on H. pyloritreatment with moxifloxacin and from the articles selected for the study werealso examined for articles meeting the inclusion criteria. Authors of someidentified trials were asked whether they knew of additional studies, includingunpublished randomized ones. In the case of duplicate reports, or studiesobviously reporting results from the same study population, only the latestpublished results were used.
Outcome Measurements And Follow
Follow-up studies to assess treatment responses were carried out for 1 week for drug compliance and adverse events assessment and 8 weeks later for H. pylori testing by urea breath tests. The primary outcome of this study was the eradication rate by intention-to-treat and per-protocol analyses of the two therapeutic groups. Eradication therapy failure was confirmed after treatment by a positive 13C-urea breath test 8 weeks after treatment. Poor compliance was the failure to finish 80% of all medication due to adverse effects.15,16 The secondary outcomes were drug compliance and adverse events. In the PP analysis, patients who were lost during follow-up or did not follow the protocol or with unknown H. pylori status posttherapy were excluded. Adverse events were compared.
Helicobacter Pylori: Current Treatment Options And Challenges
Supplements and Featured Publications
A Q& A With Colin W. Howden, MD
The American Journal of Managed Care® : What treatment options or regimens for Helicobacter pylori exist that are not reflected in the 2017 American College of Gastroenterology guidelines?
HOWDEN: The most important one thats not present in the 2017 ACG guideline is the triple combination of rifabutin, amoxicillin, and omeprazole, which was approved by the FDA in late 2019. It wasnt included in the 2017 guideline because we didnt have data about its efficacy at that time. Also of note is a clinical trial using the potassium-competitive acid blocker vonoprazan, which is not currently approved in the United States, with either amoxicillin alone or with the combination of amoxicillin and clarithromycin. Top-level results from that should be available shortly. No other established treatments have become available since 2017.
AJMC®: Which treatment regimens are currently used most often to treat H pylori?
AJMC®: What type of information about H pylori would be helpful to improving treatment outcomes?
AJMC®: How challenging would it be to adopt and implement antibiotic stewardship principles to H pylori treatment? Do you think that clinicians would support a movement toward treating H pylori based upon these principles?
AJMC®: Given the challenges of antibiotic resistance that exist and the limited access to antimicrobial sensitivity testing, what treatments are most effective?
Symptoms Of H Pylori Infection
Many people have non-severe symptoms which can lead to the belief that the infection doesnt affect them. It becomes a hidden infection that may present issues a lot later making treatment that much more complex. But for others there may be any of the following H. pylori symptoms.
The most common signs and symptoms of H. pylori we see in clinical practice are:
Heartburn or reflux, leading to GERD see below
Upper abdominal pain
How Is H Pylori Treated
If you dont have symptoms, you dont need to be treated. If youve been diagnosed with H. pylori, avoid taking nonsteroidal anti-inflammatory drugs. These drugs can increase your risk of developing an ulcer.
H. pylori-caused ulcers are treated with a combination of antibiotics and an acid-reducing proton pump inhibitor.
- Antibiotics: Usually two antibiotics are prescribed. Among the common choices are amoxicillin, clarithromycin , metronidazole and tetracycline.
- Proton pump inhibitor: Commonly used proton pump inhibitors include lansoprazole , omeprazole , pantoprazole , rabeprazole or esomeprazole .
- Bismuth subsalicylate: Sometimes this drug is added to the antibiotics plus proton pump inhibitor combinations mentioned above. This drug protects the stomach lining.
Combination treatment is usually taken for 14 days.
One newer medication, Talicia®, combines two antibiotics with a proton pump inhibitor into a single capsule.
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Current Antibiotic Resistance In Worldwide
The most important antibiotics in H. pylori treatment are clarithromycin, metronidazole, and amoxicillin. Figure illustrates recently reported clarithromycin and metronidazole resistance rates worldwide. Resistance to these antibiotics is thought to be the main cause of eradication failure. Antibiotic resistance is discovered by bacterial culture-based techniques and molecular methods . Although these methods are useful for examining antibiotic resistance, their implementation at the early stages of H. pylori remains impractical due to the time required to obtain results and the high cost of the tests.
Worldwide rates of resistance to clarithromycin and metronidazole.
Amoxicillin is a beta-lactam antibiotic that was first used for H. pylori therapy. Unlike clarithromycin and metronidazole, amoxicillin resistance rates are low worldwide: 0% or < 1% in Europe. However, other studies revealed high amoxicillin resistance rates in Iran, Japan, and Cameroon.
H Pylori Testing: How Can We Find It
A number of H. pylori testing options are available for identifying the presence of an infection. We have listed the main ones below. In our experience, DNA stool testing is the most reliable but is also prone to false negatives infections not showing up on testing like all of the options listed.
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