Treatment of Helicobacter pylori infection and factors influencing eradication

Currently available Helicobacter pylori eradication therapies are considered very effective and safe. The most recent eradication guidelines proposed in the Maastricht 2-2000 Consensus Report recommend the use of proton pump inhibitors (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of amoxycillin and clarithromycin is preferred because it may favour best results with a second-line proton pump inhibitor quadruple therapy. The recommended second-line therapy includes a combination of a proton pump inhibitor (standard b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days. Extended proton pump inhibitor-based triple therapy can be used if bismuth is not available. Specialists should manage subsequent failures. Based on direct and indirect evidence from well-designed studies and clinical experience, eradication is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis, postgastric cancer resection, and in first-degree relatives of gastric cancer patients. The most common reason for treatment failure is poor compliance with eradication guidelines. Antibiotic resistance may be a significant factor in certain geographical areas. Proton pump inhibitors are an integral part of the eradication regimens as proved by meta-analyses of clinical trials. Novel agents used in secondary failure are few and depend on the use of new antibiotics. The role of H. pylori -specific antibiotics, probiotics, and vaccines is not established as yet. Widespread acceptance of the eradication guidelines should be regarded as the single most important factor in eradication success.     

Review article: alternative antibacterial agents for Helicobacter pylori eradication

Standard eradication therapies against Helicobacter pylori appear to be effective in most cases, but in clinical practice a failure rate higher than the 5-10% reported in clinical trials is often observed. Among the various reasons responsible for therapeutic failure, antibiotic resistance is becoming a major issue in some countries. A range of different antibacterial agents is currently under investigation: several macrolides, new fluoroquinolones, furazolidone and rifabutin. Although not formally tested in refractory cases, azithromycin, spiromycin, levofloxacin and furazolidone represent the most promising antibacterial agents for possible inclusion in eradication regimens. Rifabutin has been evaluated in H. pylori infections resistant to standard therapies. Although very effective, the drug is expensive and its use should be restricted to the most difficult cases to avoid the development of rifabutin resistance in Mycobacterium spp.     

Review article: treatment of Helicobacter pylori infection and factors influencing eradication

Currently available Helicobacter pylori eradication therapies are considered very effective and safe. The most recent eradication guidelines proposed in the Maastricht 2-2000 Consensus Report recommend the use of proton pump inhibitors (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of amoxycillin and clarithromycin is preferred because it may favour best results with a second-line proton pump inhibitor quadruple therapy. The recommended second-line therapy includes a combination of a proton pump inhibitor (standard b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days. Extended proton pump inhibitor-based triple therapy can be used if bismuth is not available. Specialists should manage subsequent failures. Based on direct and indirect evidence from well-designed studies and clinical experience, eradication is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis, postgastric cancer resection, and in first-degree relatives of gastric cancer patients. The most common reason for treatment failure is poor compliance with eradication guidelines. Antibiotic resistance may be a significant factor in certain geographical areas. Proton pump inhibitors are an integral part of the eradication regimens as proved by meta-analyses of clinical trials. Novel agents used in secondary failure are few and depend on the use of new antibiotics. The role of H. pylori-specific antibiotics, probiotics, and vaccines is not established as yet. Widespread acceptance of the eradication guidelines should be regarded as the single most important factor in eradication success.     

幽门螺杆菌粪便抗原用于幽门螺杆菌感染检验观察

目的分析幽门螺杆菌粪便抗原（HpSA）对幽门螺杆菌感染的诊断价值。方法收集304例患者粪便标本,运用ELISA法定性检测HpSA,同时对照用快速尿素酶试验、Gram染色镜检联合检测的胃黏膜标本。结果HpSA的敏感度为96．7％（240／249）,特异度为90．1％（44／49）,阳性预测值为96．4％（240／249）,阴性预测值为80．0％（44／55）,准确率为93．4％（284／304）。结论粪便HpSA检测具有操作简便、省时等特点,是较理想的非侵人性的Hp诊断方法。     

Clarithromycin for Helicobacter pylori infection

Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population. Chronic H. pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence. Treatment of H. pylori has undergone substantial evolution over the past decade. Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined. The best current therapies for H. pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy). Clarithromycin is one of the most useful antimicrobials against H. pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects. Clarithromycin has a low minimum inhibitory concentration (MIC₅₀) for H. pylori and its effect is potentiated by acid inhibition. When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms. However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used. There is a need for improved therapies for H. pylori where antibiotic resistance is less of a problem.     

Clarithromycin for Helicobacter pylori infection

Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population. Chronic H. pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence. Treatment of H. pylori has undergone substantial evolution over the past decade. Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined. The best current therapies for H. pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy). Clarithromycin is one of the most useful antimicrobials against H. pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects. Clarithromycin has a low minimum inhibitory concentration (MIC50) for H. pylori and its effect is potentiated by acid inhibition. When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms. However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used. There is a need for improved therapies for H. pylori where antibiotic resistance is less of a problem.     

Use of floating alginate gel beads for stomach-specific drug delivery.

Two types of alginate gel beads capable of floating in the gastric cavity were prepared. The first, alginate gel bead containing vegetable oil (ALGO), is a hydrogel bead and its buoyancy is attributable to vegetable oil held in the alginate gel matrix. The model drug, metronidazole (MZ), contained in ALGO was released gradually into artificial gastric juice, the release rate being inversely related to the percentage of oil. The second, alginate gel bead containing chitosan (ALCS), is a dried gel bead with dispersed chitosan in the matrix. The drug-release profile was not affected by the kind of chitosan contained in ALCS. When ALCS containing MZ was administered orally to guinea pigs, it floated on the gastric juice and released the drug into the stomach. Furthermore, the concentration of MZ at the gastric mucosa after administration of ALCS was higher than that in the solution, though the MZ serum concentration was the same regardless of which type of gel was administered. These release properties of alginate gels are applicable not only for sustained release of drugs but also for targeting the gastric mucosa.     

Evolving therapy for Helicobacter pylori infection

Helicobacter pylori infection is a widespread disease causing significant morbidity and mortality, with relevant economic impact. A 7-day triple regimen (proton pump inhibitor together with two antibiotics) is currently suggested as first-line treatment, but the success rate following such a therapy is decreasing. Therefore, new drugs or novel therapeutic approaches are needed. Patents of new antibiotics have been claimed, such as both erythromycin and rifamycin derivatives, and new polycyclic compounds, showing a very powerful antibacterial activity in vitro. Patents of either H. pylori urease inhibitors or new proton pump inhibitors are also of great interest. Several attempts have been made to create vaccines for H. pylori infection, with interesting results in animal models. Experimentation in humans is ongoing.     

Novel therapies for Helicobacter pylori infection

Background:

Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection.

Aim:

To evaluate orally administered novel therapies for the treatment of H. pylori infection.

Methods:

Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1–4Glc-(3′-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present.

Results:

None of the novel therapies appeared effective and no adverse events occurred.

Conclusion:

Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.

     

Clarithromycin-amoxycillin therapy for Helicobacter pylori infection

Background: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. Methods: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. Results: H. pylori infection was cured in 86% (95% CI = 78–99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. Conclusion: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.     

Drug delivery strategies for the treatment of Helicobacter pylori infections

Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated.     

Diagnosis of Helicobacter pylori infection

Helicobacter pylori ( H.   pylori ) infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (histological examination, culture, polymerase chain reaction) and by noninvasive techniques (serology, urea breath test, urine or blood, detection of H. pylori antigen in stool specimen). At present, no single test can be absolutely relied upon to detect colonization by H. pylori , and a combination of two tests is recommended if feasible. The tests used should depend on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy, and the availability of the tests. Some clinical circumstances warrant invasive studies, principally patients with alarm symptoms (bleeding, weight loss, etc.) as well as older patients with new-onset dyspepsia. Endoscopy may also be advisable in patients who have failed eradication therapy and need culture and antimicrobial sensitivity testing to determine an appropriate regimen. Recent studies have also demonstrated that a strategy to `test and treat' for H. pylori in uninvestigated, young (< 50 years), dyspeptic patients in primary care is safe and reduces the need for endoscopy. Indeed, a number of clinical guidelines recommend noninvasive testing followed by treatment of H. pylori for dyspeptic patients in primary care based on clinical and economic analyses.     

Basis for the management of drug-resistant Helicobacter pylori infection

The discovery that most stomach diseases are a consequence of an Helicobacter pylori infection has completely changed the management of stomach diseases. Antibacterials are the treatment of choice in addition to proton pump inhibitors (PPIs) or ranitidine bismuth. We are now faced with the problem of antimicrobial resistance, which is the main cause of treatment failure. H. pylori acquires resistance essentially via point mutations, and today this phenomenon is found with most antibacterials. The most important resistance to consider is that to clarithromycin, since it is the first-choice antibacterial and clarithromycin resistance is highly clinically significant. Quadruple therapy or triple therapies with amoxicillin-metronidazole or tetracycline-metronidazole and a PPI or ranitidine bismuth can then be used despite a possible resistance to metronidazole if the strain is resistant to clarithromycin. Resistance to both clarithromycin and metronidazole may lead to the use of other combinations, i.e. amoxicillin-rifabutin, amoxicillin-levofloxacin or amoxicillin-furazolidone. Resistance to any of these drugs means their use must be avoided. In some instances, it may also be advisable to prescribe amoxicillin as the sole antibacterial, or to use a quadruple therapy with furazolidone instead of metronidazole. Although it is theoretically possible to cure a drug-resistant H. pylori infection, a practical limitation is the availability of the drugs in certain countries. Furthermore, the progressive increase in drug resistance warrants the need for new antibacterials in the near future.     

Effective regimens for the treatment of Helicobacter pylori infection

Successful Helicobacter pylori eradication therapy remains a challenge in medical practice. Currently, a proton pump inhibitor-based triple therapy containing clarithromycin, amoxicillin or nitroimidazole for 7 days is the recommended first-line treatment approach with an expected eradication success rate of ～ 80%. As a second-line treatment option in the case of failure, a ranitidine bismuth citrate-based quadruple therapy is currently recommended curing another 80% of patients, leaving a subset of patients with persistent H. pylori infection. For these patients, promising rescue options have been evaluated including regimens that contain rifabutin, quinolones, furazolidone or high-dose amoxicillin. The role of susceptibility testing is still under discussion. It is not generally recommended prior to first-line treatment but guidelines propose a role for culture and antibiotic sensitivity testing after failure of the second attempt. Meanwhile, data on the geographic distribution of resistance pattern are available and may guide therapeutic decisions with regard to the combination of antibiotics chosen for the individual patients aiming at 100% cure rate in each individual patient.     

门诊患者呼吸道感染抗菌药物使用评价

目的：探讨门诊患者呼吸道感染主要病原菌分布及其常用抗菌药物的使用情况。方法选取2010年1月~2014年1月门诊收治的829例呼吸道感染患者作为研究对象,将呼吸道黏膜作为标本进行分离、培养、鉴定,然后采用Kirby-Bauer(KB)法进行抗菌药物敏感性检测。结果829例使用抗菌药物的呼吸道感染患者共提供痰和咽拭子标本1651份,分离培养出细菌568株(30.3%),其中革兰氏阴性菌469株(81.1%),革兰氏阳性菌67株(11.8%),真菌42株(7.4%)。氧致病菌培养阳性率为34.4%。829例均有抗菌药物使用史,其中头孢菌素类368例(44.39%),氨基糖苷类278例(33.53%),大环内酯类66例(7.96%)。使用2种抗菌药物者276名(33.29%),使用3种抗菌药物者69名(8.32%)。抗菌药物的平均使用天数2.74 d。铜绿假单胞菌对哌拉西林、环丙沙星耐药率较低,肺炎克雷伯菌对头孢噻肟、头孢哌酮耐药率较低,大肠埃希菌对头孢曲松、头孢哌酮耐药率较低,金黄色葡萄球菌对头孢唑林、氧氟沙星耐药率较低。结论门诊患者呼吸道感染的主要病原菌对于一些常用抗菌药物有不同的耐药性,应依据感染菌种药敏试验的分析结果选用抗菌药物,细菌学检查是合理选用抗菌药物和减少细菌耐药的最佳方法。     

Antibiotic treatment strategies for Helicobacter pylori infection

In the third decade of the Helicobacter pylori era several informations are available on its pathogenetic mechanisms, as well as on therapeutic approaches. A 7-14 day triple or quadruple regimens (proton pump inhibitor together with 2 antibiotics) are currently suggested as first-line treatment, but the success rate following these therapy is constantly decreasing worldwide. Therefore, new drugs are needed to treat such a widespread infection. Several patents of new antibiotics have been claimed in the last 5 years, and some of them showed a very powerful antibacterial activity in vitro, even against clarithromycin and metronidazole resistant strains. Among the new compounds, thienylthiazole derivatives, benzamide derivatives and pyloricidins should be regarded as very promising molecules.     

幽门螺杆菌感染治疗的研究进展

介绍了治疗幽门螺杆菌（Helicobacter pylori,简称Hp)感染的常用药物和治疗方案，常用药物包括甲硝唑、呋喃唑酮、阿莫西林、克拉霉素和阿奇霉素等抗菌药和奥美拉唑、兰索拉唑、泮托拉唑等质子泵抑制剂（PPI）以及胶体次枸橼酸铋等，常用的治疗方案主要为含铋制的三联疗法及含PPI的三联疗法。阐述了影响Hp感染治疗效果的因素如耐药性如胃内pH等。