Helicobacter pylori infection influences nocturnal gastric acid breakthrough

BACKGROUND: Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions. AIM: To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough. METHODS: Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was determined by the 13C-urea breath test and an assay for serum anti-H. pylori antibody. RESULT: Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H2-receptor antagonist at bedtime. Only one patient with nocturnal gastric acid breakthrough had H. pylori infection. CONCLUSION: The absence of H. pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.     

Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection

Background: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multidrug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole. Methods: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks. Results: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycinbased therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%–96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%. Conclusion: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.     

One-week triple therapy with omeprazole, amoxycillin and clarithromycin for treatment of Helicobacter pylori infection

Background : Multi-drug regimens are generally required to reliably cure H. pylori infection. We previously demonstrated that a 2-week three-times-a-day regimen of amoxycillin and clarithromycin was effective against H. pylori infection.
Objectives : To evaluate the efficacy and side-effects of a 1-week twice-daily dosing schedule for the treatment of H. pylori infection.
Methods : We studied the efficacy of 1-week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H. pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture.
Results : Thirty-one patients with documented peptic ulcer disease and H. pylori infection were treated. The H. pylori infection was cured in 24 (77%, 95% CI= 58–90%) (intention-to-treat). In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI= 60–92%). One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication. Mild side-effects were reported by 16% including diarrhoea, headache and altered taste. Compliance averaged 95%. Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post-therapy.
Conclusion : This combination of omeprazole, amoxycillin and low-dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin-sensitive isolates. Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.     

Comparison of omeprazole and lansoprazole in short-term triple therapy for Helicobacter pylori infection

Background:

Effective anti-Helicobacter pylori therapies with few side-effects are needed.

Aim:

To study the effectiveness of short-term triple therapy with amoxycillin, clarithromycin and either omeprazole or lansoprazole for eradication and healing of peptic ulcers.

Methods:

Patients with gastric or duodenal ulcers received amoxycillin (1 g b.d.), clarithromycin (500 mg b.d.) and lansoprazole (30 mg b.d.) (LAC) or omeprazole (20 mg b.d.) (OAC) for 7 days. Endoscopic examinations were performed before treatment and at least 4 weeks after completion of therapy. H. pylori status was confirmed by rapid urease test and histological examination (Giemsa stain) from gastric biopsies taken from both the antrum and the body.

Results:

A total of 356 patients were randomized in this single-blind study. On a per protocol basis, H. pylori was eradicated in 134 of 170 patients (79%) in the lansoprazole group and in 105 of 146 (72%) in the omeprazole group (P = 0.189); and in intention-to-treat analysis 72% and 62%, respectively (P = 0.043). Healing of the ulcers was obtained in 166 of 186 (98%), and in 139 of 146 patients (95%), respectively (P = 0.357). Side-effects occurred in two patients in the LAC group and in six in the OAC group B (four stopped therapy).

Conclusions:

This study has shown that the two regimens are highly effective in healing duodenal ulcers and are well tolerated. Neither treatment achieves the ideal cure rate for H. pylori. Lansoprazole does not appear to have a significant advantage over omeprazole either in ulcer healing or in H. pylori eradication.

     

新三联方案根除幽门螺杆菌的疗效观察

目的观察含左氧氟沙星新三联方案对标准三联疗法根除幽门螺杆菌（Helicobacter pylori,Hp）失败患者进行补救治疗的根除效果。方法将标准三联疗法根除Hp失败的50例患者随机分为2组：治疗组给予奥美拉唑20mg＋左氧氟沙星200mg＋阿莫西林1000mg,口服7d,均2次／d;对照组给予胶体次枸橼酸铋钾200mg＋奥美拉唑20mg＋克拉霉素500mg＋阿莫西林1000mg,口服7d,均2次／d;治疗后4周行快速尿素酶试验和14C-尿素呼气试验,观察其根除率。结果50例患者中有45例完成治疗,治疗组按意图治疗（ITT）分析幽门螺杆菌根除率为76．00％（19／25）,按试验方案（PP）为82．61％（19／23）,对照组根除率按ITT为60．00％（15／25）,按PP为68．18％（15／22）,均显著低于治疗组（P〈0．05）。结论对Hp根除治疗失败的患者,新三联方案较四联疗法能获得较高的根除率,且副反应较小。     

Helicobacter pylori infection: Epidemiology, pathophysiology, and therapy

Helicobacter pylori is one of the most commonly encountered human pathogens. It has been shown to be closely associated with peptic ulcer disease (PUD), gastric adenocarcinoma, and the gastric mucosa-associated lymphoid tissue (MALT) that may lead to gastric lymphoma. The current diagnostic methods include histology, microbiological culture, classic serology, urease activity detection, polymerase chain reaction (PCR) and stool antigen detection. Its treatment modality options are multiple; however, a triple regimen consisting of a proton pump inhibitor (PPI), and two antibiotics for 10 to 14 days is preferred. Drug resistance is a growing problem in this organism and new therapeutic options are currently limited.     

The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.     

One-week triple therapy with omeprazole, amoxycillin and tinidazole for Helicobacter pylori infection: the significance of imidazole resistance

Background : Triple therapy involving a proton pump inhibitor and two antibiotics has been suggested as an effective treatment for Helicobacter pylori infection. The impact of imidazole resistance on the efficacy of such regimens is largely unknown.
Methods : One hundred patients with culture proven H. pylori infection were treated with omeprazole 40 mg b.d., amoxycillin 1000 mg b.d., and tinidazole 500 mg b.d. for one week. Pre-treatment imidazole susceptibility was measured by disk diffusion. Resistance was confirmed by E -test. Eradication was assessed by endoscopy 6–8 weeks after the end of treatment. In cases of doubt a ¹³C-urea breath test was performed. Side-effects were scored using a semiquantitative scale.
Results : H. pylori was eradicated in 95% of the patients with an imidazole-susceptible strain and in 69% of the patients with a resistant strain ( P <0.005). Significant side-effects were seen in 12%.
Conclusion : This proton pump inhibitor triple therapy is a simple, reasonably effective regimen with few significant side-effects. The efficacy is dependent on the susceptibility of the infecting H. pylori strain.     

Mouse model of Helicobacter pylori infection: studies of gastric function and ulcer healing

BACKGROUND: Helicobacter pylori infection in humans is a major risk factor for peptic ulcer, but studies on the relation between H. pylori infection and gastric pathology are limited due to a deficiency of convenient animal models resembling this infection in humans. METHODS: We studied the effects of inoculation of conventional BALB/c mice with CagA and VacA positive (type I) H. pylori or CagA and VacA negative H. pylori (type II) strains on gastric secretion and healing of chronic acetic acid-induced ulcers in mouse stomachs. The ulcer area, gastric blood flow, plasma interleukin (IL)-1beta and IL-12, as well as plasma gastrin and gastric luminal somatostatin were determined. Gastric mucosal biopsy samples were also taken for assessment of the presence of viable H. pylori using a rapid urease test, H. pylori-culture and the RT-PCR analysis of the signal for H. pylori CagA. RESULTS: Gastric acid and pepsin secretion was reduced by over 50% immediately after H. pylori inoculation and accompanied by a significant increment in plasma gastrin and fall in gastric luminal somatostatin content observed over all test days, particularly in mice infected with type I H. pylori. The area of ulcers in vehicle-treated controls decreased significantly starting from day 2 after ulcer induction and then continued to decline for a further 14 days to heal almost completely after 28 days. In contrast, the ulcers were present until day 28 in all mice infected with type I or type II H. pylori strains, being significantly larger, especially with type I H. pylori infection. The gastric blood flow at the ulcer margin and ulcer crater in vehicle-treated mice gradually increased with decreasing ulcer size, after 14 and 28 days reaching a value which was not significantly different from that in vehicle-administered mice. In contrast, the gastric blood flow in type I H. pylori and, to a lesser extent, in type II H. pylori infected mice was significantly lower than in vehicle controls, both at the margin and at the crater of ulcers at all tested days. Histological changes such as oedema or congestion of surface epithelium were found after 7 days whereas mucosal inflammatory infiltration appeared after 14 days with a further increase after 28 days, especially in type I H. pylori and to a lesser extent in type II H. pylori infected mice. Plasma IL-1beta and IL-12 were significantly elevated at all tested days of ulcer healing and their increments were significantly higher in type I than in type II H. pylori infection. CONCLUSIONS: Conventional mice with gastric ulcers can be successfully infected by both toxigenic and nontoxigenic H. pylori strains, and this infection causes an immediate suppression of gastric secretion and markedly delays the healing of ulcers due to the fall in mucosal microcirculation in the ulcer region, cytokine release and an impairment in the gastrin-somatostatin link that appears to be independent of gastritis and more pronounced with infection of toxigenic than nontoxigenic strains.     

One-week triple therapy with omeprazole, amoxycillin and either clarithromycin or metronidazole for cure of Helicobacter pylori infection

Aim: The present study was designed to evaluate the efficacy and tolerability of 1-week triple therapy regimens for Helicobacter pylori .
Methods: In two consecutive series, 120 patients with proven H. pylori infection and peptic ulcer disease or functional dyspepsia were treated with either omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (OAC; n=60) or with omeprazole 20 mg b.d., amoxycillin 1 g b.d. and metronidazole 400 mg b.d. over 1 week (OAM; n=60). H. pylori infection was assessed by rapid urease test, culture and histology before and 4 weeks after cessation of the eradication therapy.
Results: H. pylori eradication succeeded in 53 out of 60 patients by omeprazole–amoxycillin–clarithromycin (OAC) (88%; 95% CI 77–95%) and in 47 out of 60 patients by omeprazole–amoxycillin–metronidazole (OAM) (78%; 95% CI 66–88%) (P=0.22). Nine patients of each group available for follow-up reported adverse events (15.0 and 15.5%, respectively) without necessity of discontinuation of the study medications. Serious adverse events were not observed.
Conclusions: Simple and convenient 1-week triple therapies consisting of omeprazole, amoxycillin and either clarithromycin or metronidazole are sufficiently effective in eradicating H. pylori infection.     

埃索美拉唑三联与奥美拉唑三联治疗Hp阳性十二指肠溃疡的对比研究

目的:比较埃索美拉唑三联与奥美拉唑三联疗法治疗幽门螺杆菌(Hp)阳性十二指肠球部溃疡的临床疗效。方法:将124例经内镜诊断并检测证实Hp阳性的十二指肠球部溃疡患者随机分为两组。埃索美拉唑组(62例):埃索美托唑20mg加阿莫西林lg加克拉霉素500mg,每日2次,共7天;奥美拉唑组(62例):奥美拉唑20mg加阿莫西林1g加克拉霉素500mg,每日2次,共7天。疗程结束4周后胃镜检查并检测Hp,观察腹痛缓解率、溃疡愈合率、Hp根除率及药物不良反应。结果:埃索美拉唑组第一天和第二天腹痛缓解率分别为35.8%和60.2%,高于奥美托唑组的16.5%和40.3%(P<0.05)。埃索美托唑组和奥美拉唑组溃疡愈合率分别为93.6%和89.5%,Hp根除率分别为87.9%和83.7%,差异无显著性(P>0.05)。两组药物不良反应少,有较好的安全性。结论:埃索美托唑三联疗法治疗Hp阳性的十二指肠溃疡安全有效。腹痛状缓解速度明显优于奥美拉唑三联疗法。     

Double gastric infection with Helicobacter pylori and non-Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritis

BACKGROUND: Long-term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori-positive subjects. The pathogenetic mechanism remains unclear. AIM: To test the hypothesis that gastric double infection with H. pylori and non-H. pylori bacterial species-during acid suppression-may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis. PATIENTS AND METHODS: A consecutive series of patients with gastro-oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2-receptor antagonists (H2-RAs) (n=37), and 76 non-treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non-H. pylori bacteria, histological gastritis, H. pylori serology, and circulating interleukin (IL)-1beta, IL-6, and IL-8 were examined. RESULTS: Patients on acid suppression with either proton pump inhibitors or H2-RAs had a similar prevalence of H. pylori infection to the controls, but a higher prevalence of non-H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non-H. pylori bacteria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous presence of H. pylori and non-H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL-1beta and IL-8). SUMMARY AND CONCLUSIONS: H. pylori-positive patients on long-term acid inhibition displayed three features: non-H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non-H. pylori bacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition.     

Treatment of Helicobacter pylori infection with a combination of itraconazole and omeprazole

Aim : To determine the in vivo anti-microbial activity of a high-dose itraconazole and omeprazole regimen against Helicobacter pylori. Methods: In an open pilot study, 10 H. pylori positive dyspeptic patients were treated with itraconazole 200 mg b.d. and omeprazole 200 mg b.d. for 7 days. Follow-up upper gastrointestinal endoscopy was performed 4–5 weeks after completion of therapy. Eradication of H. pylori infection was determined by histopathological examination and culture of biopsies from the antrum and corpus. Results: Eradication was not observed in any patient. Conclusion: This combination of itraconazole with omeprazole does not eradicate H. pylori infection.     

The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia

BACKGROUND: Dysmotility of the gastroduodenal region and delayed gastric emptying have been considered to play roles in non-ulcer dyspepsia (NUD). Helicobacter pylori-induced inflammation of the gastric mucosa may affect gastric motility. AIM: To evaluate the effects of H. pylori eradication therapy on gastrointestinal motility and symptoms in NUD patients. METHODS: : Forty-six NUD patients were examined for gastric emptying, antral myoelectrical activity, H. pylori infection, and symptom scores. In H. pylori-positive NUD patients, gastric emptying, antral myoelectrical activity, and symptom scores were also analysed 2 months after cure of H. pylori infection. RESULTS: Sixty-seven per cent of NUD patients were H. pylori-positive. Both abnormal gastric emptying and antral myoelectrical activity were observed in NUD patients. H. pylori-positive NUD patients were divided into three groups according to their gastric emptying: the delayed group, the normal group, and the rapid group. In the delayed and rapid gastric emptying groups, the emptying and symptom scores were improved significantly by eradication. There was no improvement in symptom scores in the normal gastric emptying NUD group by the eradication therapy. CONCLUSIONS: Disturbed gastric emptying and antral myoelectrical activity play roles in NUD. H. pylori-induced disturbed gastric emptying may cause some NUD symptoms. Gastric emptying and symptom scores are improved by H. pylori eradication therapy in NUD patients with disturbed gastric emptying; H. pylori eradication therapy is effective in H. pylori-positive NUD patients with disturbed gastric emptying.     

有上消化道症状患者幽门螺杆菌感染情况分析及其与胃癌前病变的关系

目的 分析幽门螺杆菌(Hp)感染与胃癌前病变、胃癌的关系.方法 对6年中门诊胃镜检查的106780例患者进行快速尿素酶试验检测Hp,并结合活检病理报告,对Hp感染与年龄、胃癌前病变、胃癌进行回顾性统计分析.结果 Hp感染率由2006年的36.3％降至2011年的24.2％.20-29岁组Hp感染率为34.9％,明显高于40-49岁组的31.4％、50-59岁组的28.5％和＞60岁组的24.8％(P＜0.05).6年中,Hp感染患者中肠化生、胃癌发生率均明显下降(P＜0.05),高级别上皮内瘤变发生率明显上升(P＜0.05).肠化生、上皮内瘤变、胃癌患者中Hp感染率均显著下降(P＜0.05).结论 6年间胃镜检查患者中Hp感染率逐年下降,Hp感染在青中年中居多,胃癌前病变及胃癌患者的Hp感染率下降.     

Changes of gastric mucosal architecture during long-term omeprazole therapy: results of a randomized clinical trial

Background The impact of long‐term acid suppression on the gastric mucosa remains controversial. Aim To report further observations on an established cohort of patients with gastro‐oesophageal reflux disease, after 7 years of follow‐up. Methods Of the original cohort randomized to either antireflux surgery or omeprazole, 117 and 98 patients remained in the medical and surgical arms, respectively. Gastric biopsies were taken at baseline and throughout the study. Results Fifty‐three antireflux surgery and 39 omeprazole‐treated patients had Helicobacter pylori infection at randomization. Eighty‐three omeprazole‐treated and 60 antireflux surgery patients remained H. pylori negative over the 7 years, and no change was observed in mucosal morphology except for a change in endocrine cell population (linear and diffuse hyperplasia, P = 0.03). During the 7‐year study many patients, who were initially H. pylori infected, had the infection eradicated leaving only 13 omeprazole and 12 antireflux surgery patients still infected. In these patients, omeprazole induced a deterioration of the mucosal inflammation scores (P = 0.01) with a numerical increase of glandular atrophy. Conclusions Long‐term omeprazole therapy does not alter the exocrine oxyntic mucosal morphology in H. pylori‐negative patients, but mucosal endocrine cells appear to be under proliferative stimulation; in H. pylori‐positive patients there are changes in mucosal inflammation and atrophy.     

Intragastric distribution of Helicobacter pylori during short-term omeprazole therapy: study using Carnoy's fixation and immunohistochemistry for detection of bacteria

BACKGROUND: There is controversy about the effect of acid-suppressive therapy on Helicobacter pylori density and the severity of histological gastritis in the corpus. AIM: To evaluate the precise distribution of H. pylori, both on the surface mucus cells and in the surface mucus gel layer, by using Carnoy's fixation and immunostaining for the detection of bacteria. METHODS: A total of 19 peptic ulcer patients with H. pylori infection were studied. All patients received a 6-week course of treatment with omeprazole (20 mg/day). Before and after the therapy, H. pylori density in Carnoy-fixed tissue sections was examined immunohistochemically. The effect of omeprazole therapy on the severity of gastritis was also evaluated. RESULTS: H. pylori density and the grade of gastritis significantly decreased in the antrum after omeprazole therapy. In the corpus, however, there were no significant changes in H. pylori density or the severity of gastritis after omeprazole therapy. CONCLUSION: Carnoy's fixation and immunostaining was found to be useful for the detection of H. pylori in the surface mucus gel layer as well as on the surface mucus cells in biopsy tissue sections. By using this method, H. pylori density decreased in the antrum, but remained unchanged in the corpus after a 6-week course of omeprazole therapy.     

多西环素、左氧氟沙星参与的序贯疗法治疗胃幽门螺旋杆菌感染

目的：研究分析多西环素、左氟氧沙星参与的序贯疗法对胃幽门螺旋杆菌感染（HP）的治疗效果。方法：将我院2014年8月～2015年12月收治的胃幽门螺旋杆菌感染患者120例,分为A组和B组各60例。 A组采用序贯疗法进行治疗,患者前3d服用雷贝拉唑、甲硝唑、阿莫西林,后7d服用雷贝拉唑、多西环素、左氟氧沙星。B组口服雷贝拉唑、甲硝唑、阿莫西林,疗程为10d。统计分析两组患者的症状评分、溃疡面积、疗效以及不良反应发生率。结果：治疗后两组的临床症状及溃疡面积均有所改善,A组的临床症状积分及溃疡面积均显著小于B组（P＜0.05）。A组的总有效率、HP清除率高于B组（P＜0.05）。两组患者不良反应总发生率无差异（P﹥0.05）。结论：多西环素、左氟氧沙星参与的序贯疗法可降低HP的耐药性,提高HP清除率,疗效优于传统疗法,值得推广。