Role of metronidazole resistance in therapy of Helicobacter pylori infections.

Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate.     

Recurrence rate of H. pylori after successful eradication and second eradication therapy after initial failure of treatment

Three hundred thirty-three patient (116 gastric ulcer, 119 duodenal ulcer, 98 gastritis) who were successfully eradicated were enrolled in the study of H. pylori recurrence rate. H. pylori status was determined by histology, rapid urease test, 13C-urea breath test. The mean of the follow-up period was 13.3 months (2-56 months), and 15 patients showed negative to positive conversion of H. pylori. The recurrence rate was 4.4% for one year and 8.3% for two years using Kaplan-Meier analysis. Second eradication therapy after initial failure is another concern. Nineteen patients were assigned to receive an 1-week new triple therapy (clarithromycin, metronidazole and PPI), in whom a 2-week course of dual therapy (amoxicillin plus PPI) failed (group1). Another 15 patients in whom the 1-week new triple therapy failed were switched to the 2-week course of dual therapy plus ecabet sodium (group2). H. pylori was eradicated in 84.2% (16/19) of patients in group1 and 86.7% (13/15) in group2.     

Helicobacter pylori eradication: efficacy and side effect profile of a combination of omeprazole, amoxycillin and metronidazole compared with four alternative regimens

We evaluated eradication of Helicobacter pylori infection in263 patients by a new 14-day regimen of omeprazole 40 mg mane(a gastric secretory inhibitor) plus two antibiotics: amoxycillin500 mg three-times daily (tds) plus metronidazole 400 mg tds.The comparative groups included updated results of our previouswork 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 allthree components (colloidal bismuth subcitrate 120 mg, tetracycline500 mg, metronidazole 200 mg) qds instead of tds, or Logan's(ITT) seven-day therapeutic regimen of colloidal bismuth subcitrate120 mg qds, amoxycillin 500 mg qds and, for the last three days,metronidazole 400 mg five times daily. Omeprazole/amoxycillin/metronidazole (OAM) therapy was bettertolerated 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 were20/22 (90.9%) and 14/29 (48.3%), (metronidazole-sensitive organisms)and 7/21 (33.3%) and 15/31 (48.4%) (infections resistant tometronidazole). BTT and LTT were also better tolerated than STT. The eradicationrate for BTT was 23/26 (88.5%) but that for LTT, the best toleratedof the five treatment regimens, was only 19/28 (67.9%) whenpretreat-ment isolates were metronidazole-sensitive. OAM therapywas better tolerated than either STT or BTT. With metronidazole-sensitiveorganisms, 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 thanSTT (95% Cl 19.2–64.2). These results support our current practice of prescribing OAMfor patients with duodenal ulcer infected with H. pylori, reservingBTT for patients allergic to penicillin.     

Helicobacter pylori eradication: efficacy and side effect profile of a combination of omeprazole, amoxycillin and metronidazole compared with four alternative regimens

We evaluated eradication of Helicobacter pylori infection in263 patients by a new 14-day regimen of omeprazole 40 mg mane(a gastric secretory inhibitor) plus two antibiotics: amoxycillin500 mg three-times daily (tds) plus metronidazole 400 mg tds.The comparative groups included updated results of our previouswork 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 allthree components (colloidal bismuth subcitrate 120 mg, tetracycline500 mg, metronidazole 200 mg) qds instead of tds, or Logan's(ITT) seven-day therapeutic regimen of colloidal bismuth subcitrate120 mg qds, amoxycillin 500 mg qds and, for the last three days,metronidazole 400 mg five times daily. Omeprazole/amoxycillin/metronidazole (OAM) therapy was bettertolerated 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 were20/22 (90.9%) and 14/29 (48.3%), (metronidazole-sensitive organisms)and 7/21 (33.3%) and 15/31 (48.4%) (infections resistant tometronidazole). BTT and LTT were also better tolerated than STT. The eradicationrate for BTT was 23/26 (88.5%) but that for LTT, the best toleratedof the five treatment regimens, was only 19/28 (67.9%) whenpretreat-ment isolates were metronidazole-sensitive. OAM therapywas better tolerated than either STT or BTT. With metronidazole-sensitiveorganisms, 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 thanSTT (95% Cl 19.2–64.2). These results support our current practice of prescribing OAMfor patients with duodenal ulcer infected with H. pylori, reservingBTT for patients allergic to penicillin.     

Resistance of Helicobacter pylori isolated in Israel to metronidazole,clarithromycin, tetracycline,amoxicillin and cefixime

The resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime was tested in 138 isolates, including 28 from treatment failures. No resistance to tetracycline was detected. Resistance to amoxicillin was found in one isolate (MIC = 1.5 mg/L) from an untreated patient, and resistance to cefixime in two isolates from each group (P = 0.18). Resistance to metronidazole and clarithromycin was much higher in the isolates from treated than from untreated patients: 60.7% and 38.2% for metronidazole (MIC >or= 8 mg/L) (P = 0.03); 46.4% and 8.2% for clarithromycin (MIC >or= 2 mg/L) (P < 0.001). Therapeutic outcome would benefit from susceptibility testing, especially after treatment failure.     

两种方案治疗十二指肠溃疡幽门螺杆菌感染的临床分析

目的分析小剂量奥关拉唑、左氧氟沙星及呋喃唑酮新三联与小剂量奥关拉唑、阿莫西林及甲硝唑标准三联疗法治疗十二指肠溃疡幽门螺杆菌(Helicobacter pylori,Hp)感染的临床疗效对比。方法98例符合条件的患者随机分成两组,其中47例为新三联疗法,即口服小剂量奥美拉唑20mg,1次／d,连服6周,左氧氟沙星200mg及呋喃唑酮200mg,均为2次／d,连服2周。另一组51例为标准三联疗法,即口服小剂量奥关拉唑20mg,1次／d,连服6周,阿莫西林1000mg及甲硝唑400mg,均为2次／d,连服2周,疗程结束后1个月复查胃镜。结果96例患者完成治疗及随访,小剂量奥美拉唑新三联组与小剂量奥关拉唑标准三联组疗法Hp根除率分别为84．8％、82．0％,差异无统计学意义(P=0．715);溃疡愈合率分别为95．7％、92．0％,差异无统计学意义(P=0．752)。两组患者不良反应发生率分别为12．8％、15．7％,差异无统计学意义(P=0．680)。HP根除组溃疡愈合率(100．0％)明显高于HP未根除组(62．5％),差异有统计学意义(P=0．001)。结论小剂量奥关拉唑新三联组与标准三联组疗法均有较理想的Hp根除率及溃疡愈合率,新三联组疗法不良反应发生率与标准三联组疗法相当;同时发现Hp根除有利于溃疡愈合。因此,在当今面临Hp对常规抗生素耐药率上升的情况下,推荐新三联疗法在阿莫西林及甲硝唑耐药地区可作为根除十二指肠溃疡HP感染的一线治疗或失败后的补救治疗方案。     

Exposure to metronidazole in vivo readily induces resistance in Helicobacter pylori and reduces the efficacy of eradication therapy in mice

The Helicobacter pylori SS1 mouse model was used to characterize the development of resistance in H. pylori after treatment with metronidazole monotherapy and to examine the effect of prior exposure to metronidazole on the efficacy of a metronidazole-containing eradication regimen. Mice colonized with the metronidazole-sensitive H. pylori SS1 strain were treated for 7 days with either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole once a day or three times per day (TID). In a separate experiment, H. pylori-infected mice were administered either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole TID for 7 days, followed 1 month later by either peptone trypsin broth or the mouse equivalent of 20 mg of omeprazole, 250 mg of clarithromycin, and 400 mg of metronidazole twice a day for 7 days. At least 1 month after the completion of treatment, the mice were sacrificed and their stomachs were cultured for H. pylori. The susceptibilities of isolates to metronidazole were assessed by agar dilution determination of the MICs. Mixed populations of metronidazole-resistant and -sensitive strains were isolated from 70% of mice treated with 400 mg of metronidazole TID. The ratio of resistant to sensitive strains was 1:100, and the MICs for the resistant strains varied from 8 to 64 micrograms/ml. In the second experiment, H. pylori was eradicated from 70% of mice treated with eradication therapy alone, compared to 25% of mice pretreated with metronidazole (P < 0.01). Mice still infected after treatment with metronidazole and eradication therapy contained mixed populations of metronidazole-resistant and -sensitive isolates in a ratio of 1:25. These results demonstrate that H. pylori readily acquires resistance to metronidazole in vivo and that prior exposure of the organism to metronidazole is associated with failure of eradication therapy. H. pylori-infected mice provide a suitable model for the study of resistance mechanisms in H. pylori and will be useful in determining optimal regimens for the eradication of resistant strains.     

Proton pump inhibitor-amoxicillin-clarithromycin versus proton pump inhibitor-amoxicillin-metronidazole as first-line Helicobacter pylori eradication therapy

The aim of this study was to compare the efficacy and tolerability of the first-line Helicobacter pylori (H. pylori) eradication regimen composed of proton pump inhibitor, clarithromycin, and amoxicillin, with those of a regimen composed of proton pump inhibitor, metronidazole, and amoxicillin. Data of patients, who were administered the first-line H. pylori eradication regimen at Tokyo Medical Center between 2008 and 2011, were reviewed. All patients had H. pylori gastritis without peptic ulcer disease. The 7-day triple regimen composed of lansoprazole, clarithromycin, and amoxicillin was administered to 55 patients, and that composed of omeprazole, metronidazole, and amoxicillin was administered to 55 patients. Intention-to-treat and per-protocol eradication rates were 74.5 and 80.4%, respectively, for the regimen of lansoprazole, clarithromycin, and amoxicillin, whereas the corresponding rates were 96.4 and 100%, respectively, for the regimen of omeprazole, metronidazole, and amoxicillin. In conclusion, first-line H. pylori eradication therapy composed of omeprazole, metronidazole, and amoxicillin was significantly more effective than that composed of lansoprazole, clarithromycin, and amoxicillin, without differences in tolerability.     

Comparison of the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication regimens for<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

AIMS AND METHODS: The aim of this study was to compare the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication of H. pylori infection. 235 patients with H. pylori infections and non-ulcer dyspepsia were randomly assigned to one of the following regimens: lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 250 mg (LAC250) and lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 500 mg (LAC500). All drugs were given twice daily for 7 days. The patients were assessed for prevalence of H. pylori with the CLO test. Gastric biopsy samples obtained during upper gastrointestinal endoscopy before randomization and 4-6 weeks after completion of therapy were used for histology and culture. Bacterial sensitivity to clarithromycin and amoxicillin was determined with the E-test. RESULTS: 101 patients in the LAC250 mg group and 102 in the LAC500 group completed the study. On intention-to-treat analysis, eradication rates were 81% with LAC250 and 82% with LAC500 (p=0.88). On per-protocol analysis, eradication rates were 92% with LAC250 and 96% with LAC500 (p=0.23). Among the 203 patients (86% of the entire study group) for whom H. pylori antibiotic-sensitivity testing was technically feasible, primary resistance to clarithromycin was found in 9% and to amoxicillin in 0%. Eradication of clarithromycin sensitive/resistant strains was 94%/38% for LAC250 (p < 0.001) and 93%/40% for LAC500 (p < 0.001). CONCLUSIONS: The cure rates for the two regimens were similar, although adverse effects were more frequent with the LAC500 regimen, suggesting that 250 mg of clarithromycin b.d. may be sufficient in our patient population.     

Appearance of a metronidazole-resistant Helicobacter pylori strain in an infected-ICR-mouse model and difference in eradication of metronidazole-resistant and -sensitive strains.

We tested whether antibiotic-resistant strains appeared in vivo after the failure of treatment using the Helicobacter pylori-infected euthymic mouse model. The numbers of colonies isolated from 56 ICR mice 2 weeks after 4 days of treatment with metronidazole (3.2, 10, or 32 mg/kg of body weight) or amoxicillin (1, 3.2 or 10 mg/kg), with treatment started 4 days after H. pylori CPY2052 inoculation, were counted, and the isolated strains were tested for their sensitivities to two antibiotics to rule out the presence of antibiotic-resistant strains. One metronidazole-resistant strain was detected in a mouse treated with 10 mg of metronidazole per kg, and the MIC of metronidazole for this strain was 25 microg/ml, compared to a MIC of 1.56 microg/ml for the original strain. However, no resistant strain was detected in the amoxicillin treatment group. After the examination described above, mice challenged with a metronidazole-resistant or -sensitive strain isolated from the stomach of a mouse were treated with metronidazole or amoxicillin. The metronidazole-resistant strain was more difficult to eradicate in vivo than the sensitive strain after treatment with metronidazole but not after treatment with amoxicillin. Thus, a metronidazole-resistant H. pylori strain was selected by insufficient treatment, but no resistant strain was selected with amoxicillin. Eradication of a metronidazole-resistant H. pylori strain in vivo required a higher dosage than eradication of a metronidazole-sensitive H. pylori strain. These results may explain one of the reasons for H. pylori treatment failure.     

阿奇霉素三联疗法根除幽门螺杆菌的疗效观察──附69例报告

目的:观察阿奇霉素三联疗法根除十二指肠球部溃疡病人的幽门螺杆菌(Hp)的临床疗效,对比阿奇霉素三联疗法一周与两周方案的疗效差别。方法:69例经胃镜检查证实为十二指肠球部溃疡并有Hp感染的病人,随机分为两组。A组(35例)口服奥美拉唑40mg每日1次,共2周;阿奇霉素500mg/d,仅疗程开始的头3日口服;阿莫西林500mg口服,每日4次,共2周。B组(34例)奥美拉唑与阿奇霉素的剂量和疗程同A组,阿莫西林500mg口服,每日3次,共1周。疗程结束后停用所有抗生素,4周后胃镜复查溃疡愈合情况,14C-尿素呼气试验复查Hp根除情况。结果:Hp根除率:A组和B组分别为89%(31/35)、85%(29/34),两组比较无显著性差异(P>0.05);溃疡愈合率:A组和B组分别为97%(28/29)、94%(29/31),两组比较无显著性差异(P>0.05);全部病人均完成治疗,仅2例出现恶心,1例轻度腹泻,总不良反应率为4%。结论:①阿奇霉素三联疗法具有Hp根除率高、安全性好、不良反应少及依从性好的优点;②阿奇霉素三联疗法一周方案与两周方案比较疗效相当;③阿奇霉素可作为根除Hp治疗方案中的一个新选择。     

石家庄地区幽门螺杆菌临床分离株耐药性分析

目的了解石家庄地区幽门螺杆菌(Helicobacter pylori,H.pylori)临床分离株对多种抗生素的耐药状况,为选择有效的H.pylori根除方案提供临床指导。方法收集200例H.pylori感染的患者,对其胃黏膜活检组织进行H.pylori分离培养,采用Kirby-Bauer法检测H.pylori临床分离株对甲硝唑、克拉霉素、阿莫西林、左氧氟沙星、呋喃唑酮、四环素等6种抗生素的耐药率。结果从200例患者中分离出121株H.pylori,阳性率60.5%,不同性别、年龄的培养阳性率差异无统计学意义(P0.05);H.pylori对甲硝唑、克拉霉素、阿莫西林、左氧氟沙星、呋喃唑酮和四环素的耐药率分别为95.0%(115/121)、26.4%(32/121)、2.5%(3/121)、5.8%(7/121)、0和3.3%(4/121)。不同性别、年龄的耐药率差异无统计学意义(P0.05)。结论石家庄地区H.pylori对甲硝唑、克拉霉素的耐药率较高,这些药物不宜作为治疗H.pylori的一线药物;阿莫西林、左氧氟沙星、呋喃唑酮和四环素的耐药率较低,可作为治疗H.pylori感染的主要药物。     

Monotherapy with mastic does not eradicate Helicobacter pylori infection from mice

OBJECTIVE: To determine the ability of mastic monotherapy to eradicate Helicobacter pylori infection from mice. MATERIALS AND METHODS: The susceptibility of H. pylori SS1 to mastic was assessed by broth dilution determination of the MIC and MBC. Mice were inoculated intragastrically with either a suspension of H. pylori SS1 (n = 70) or brain-heart infusion broth alone (n = 10). Mice were given antimicrobial chemotherapy 4 weeks after infection and were administered the mouse equivalent of either 2 g of mastic twice daily for 7 days or a triple therapy regimen containing the mouse equivalent of 400 mg of metronidazole, 250 mg of clarithromycin and 20 mg of omeprazole twice daily for 7 days. Mice were killed either immediately or 1 month after the completion of treatment, and their stomachs cultured for H. pylori. RESULTS: The mastic MIC and MBC of H. pylori SS1 were 7.80 and 31.25 mg/L, respectively. The triple therapy regimen eradicated infection from 19 of 20 SS1-infected mice. Mastic failed to eradicate infection from any of the 18 SS1-infected mice (P < 0.001) and there was no signifi- cant reduction in gastric bacterial load in mice treated with this regimen. CONCLUSION: Despite reported beneficial effects in ulcer patients and the good in vitro activity of mastic against H. pylori, this compound is unable to eradicate H. pylori infection from mice.     

Standardization of disk diffusion test and its clinical significance for susceptibility testing of metronidazole against Helicobacter pylori.

Susceptibilities of 121 clinical Helicobacter pylori strains to metronidazole were determined by both a 5-micrograms metronidazole disk diffusion test and a plate dilution method in duplicate and after different periods of incubation. The distribution of MICs of metronidazole against H. pylori among the strains was found to be bimodal. The diameters of inhibitory zones obtained by the disk diffusion test and the MICs obtained by the plate dilution method correlated well, especially after 4 days of incubation (r = 0.77). An inhibitory zone diameter of 20 mm was found to correspond to a MIC of 8 micrograms/ml and is recommended as a suitable zone for differentiating susceptibility and resistance with a 5-micrograms metronidazole disk. Three interpretive categories of susceptibility results were defined; strains with inhibitory zone diameters of more than 26 mm were defined as susceptible (MIC, < 4 micrograms/ml), strains with zone diameters of 20 to 26 mm were deemed intermediate (MIC, 4 to 8 micrograms/ml), and those with zone diameters of less than 20 mm were deemed resistant (MIC, > 8 micrograms/ml). Furthermore, 76 H. pylori-positive patients with duodenal ulcers or nonulcer dyspepsia were treated with a 1 week of triple therapy (colloidal bismuth subcitrate, metronidazole, and tetracycline). H. pylori strains were isolated before treatment from antral biopsies from those patients, and the metronidazole susceptibilities of the strains were determined by the disk diffusion test. H. pylori status was evaluated again 4 weeks after completion of treatment. The eradication rates for susceptible, intermediate, and resistant strains were 95.9% (47 of 49), 62.5% (5 of 8), and 52.6% (10 of 19), respectively. It is included that the 5-micrograms disk diffusion test is easy to perform and gives final results similar to those of the plate dilution method. The three interpretive categories of susceptibility may be of benefit for clinical choice of chemotherapy in eradicating H. pylori.     

Selection of antibiotics and planning of eradication for H. pylori infection

There is general agreement that H. pylori should be eradicated in patients with peptic ulcers. But the optimal therapeutical regimen to be used still remains a matter for many investigations. An increase in the prevalence of antibiotic-resistant H. pylori strains has been reported recently. The recommended drugs for the eradication in Japan are clarithromycin (CAM) and amoxicillin (AMPC) because metronidazole (MNZ) is anti-parasites drug in Japan. A total of 392 H. pylori strains in the last twelve years were tested for sensitivity to CAM, MNZ, and AMPC. The Primary resistance of H. pylori to CAM, MNZ, and AMPC were found in 10.2%, 26.5%, and 0.3% strains, respectively. The resistant strains to CAM were gradually increasing in the last few years. The eradication therapies which do not increase antibiotics resistant strains after eradication failure were reported. The recommendation for eradication in patients with peptic ulcer disease includes those with bleeding ulcers. The pretreatment with proton pump inhibitors (PPI) does not influence the success of PPI-based triple therapy in eradicating H. pylori.     

Helicobacter pylori antibiotic resistance patterns and genotypes in adult dyspeptic patients from a regional population in North Wales

OBJECTIVE: Surveillance data on Helicobacter pylori antibiotic susceptibilities in Wales are limited, despite resistance being a key factor in treatment failure. A single-centre survey was undertaken over 3 years to determine local antibiotic resistance rates on isolates from dyspeptic patients in Bangor, Gwynedd (North Wales). METHODS: Susceptibilities were determined for 363 isolates by disc diffusion and the Etest. Isolates were also genotyped (cagA presence and vacA allelic types). RESULTS: Overall in vitro resistance rates were 24% for metronidazole and 7% for clarithromycin, with 4% resistant to both antibiotics. Resistant strains typically had high MICs of >256 mg/L. Tetracycline resistance was identified in only one isolate whereas no isolates showed resistance to amoxicillin. There was a two-fold increase in resistance over the study period. No gender and age associations with resistance were detected. Resistant and susceptible isolates were genotypically diverse with respect to cagA/vacA type but the vacA s1m2 form was a feature of all clarithromycin-resistant isolates compared with 56% of the susceptible isolates. CONCLUSION: Although the overall antibiotic resistance rates of H. pylori from North Wales were low compared with many other regions in Europe, continued surveillance, particularly of high-level resistance (MIC >256 mg/L), is recommended to monitor the effects of the 'test and treat' strategy for H. pylori eradication.     

High eradication rate of H. pylori with moxifloxacin-based treatment: a randomized controlled trial

INTRODUCTION: Eradication of Helicobacter pylori remains a problematic treatment issue in clinical practice. The intention is to find a treatment that achieves a high rate of eradication at a low price and treatment options that are now used give us the opportunity to achieve this goal. Recently published results showing a low rate of resistance and better compliance with moxifloxacin-based treatment regimens indicate the need to investigate its efficacy in H. pylori eradication. This study is based on proving the efficacy of moxifloxacin in H. pylori eradication within the triple therapy. AIMS AND METHODS: The aim of the study was to compare the efficacy of one week of moxifloxacin-based treatment with the standard treatment for H. pylori eradication. Patients with H. pylori infection and non-ulcer dyspepsia (n = 277) were randomly divided into four groups to receive: moxifloxacin 400 mg/d, metronidazole 400 mg twice daily, lansoprazole 30 mg twice daily (MML group); moxifloxacin 400 mg/d, amoxicillin 1 g twice daily, lansoprazole 30 mg twice daily (MAL group); clarithromycin 500 mg twice daily, metronidazole 400 mg twice daily, lansoprazole 30 mg twice daily (CML group); clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, lansoprazole 30 mg twice daily (CAL group). The patients were assessed for prevalence of H. pylori using the CLO test, histology and culture on gastric biopsy samples obtained during upper gastrointestinal endoscopy before randomization and 4-6 weeks after completion of treatment. Bacterial sensitivity to clarithromycin and moxifloxacin was determined with the E-test. RESULTS: 265 (95.6%) patients completed the study forming the basis for PP analysis. Eradication rates of H. pylori in ITT and in PP analyses were: in the MML group 93.5% (58/62) and 96.7% (58/60), respectively; in the MAL group 86.4% (57/66) and 90.5% (57/63); in the CML group 70.4% (50/71) and 75.8% (50/66); and in the CAL group 78.2% (61/78) and 80.2% (61/76). Moxifloxacin treatment protocols were significantly more effective on both ITT and PP analyses than the clarithromycin based protocols with only one exception (MAL vs. CAL on ITT analysis). Among 238 patients (86% of the entire study group), strains showing primary resistance to clarithromycin were found in 10.8% and to moxifloxacin in 5.9%. Eradication of moxifloxacin sensitive/resistant strains was 98.1%/75% for MML (p < 0.01) and 91.1%/66.7% for MAL (p = n.s.); comparison of eradication of sensitive strains in MML and MAL regimens was 98.1%/91.1% (p < 0.05), and for resistant strains 75%/66.7% (p = n.s.). CML and CAL protocols did not differ in efficacy of eradication of clarithromycin sensitive or resistant strains. CONCLUSION: Moxifloxacin-based triple therapies showed higher eradication rates with few side effects and good drug compliance when compared with standard H. pylori treatments. Moreover, the increased prevalence of clarithromycin resistance suggests that moxifloxacin-based regimens could be safe and effective options in treatment of H. pylori infection.     

雷贝拉唑与兰索拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡疗效比较

目的:比较雷贝拉唑三联疗法与兰索拉唑三联疗法治疗幽门螺杆菌阳性消化性溃疡的疗效。方法:将幽门螺杆菌阳性的消化性溃疡83例分为两组:治疗组(雷贝拉唑三联疗法组)41例,以雷贝拉唑10mg,阿莫西林1000mg及甲硝唑400mg每日2次口服,治疗1周后单独服用雷贝拉唑10mg,连服7d;对照组(兰索拉唑三联疗法组)42例:以兰索拉唑30mg,阿莫西林1000mg及甲硝唑400mg,每日2次口服,治疗1周后单独服用兰索拉唑30mg,连服7d。治疗期间每周门诊随诊,记录临床症状改善情况,用药结束1个月后复查胃镜并检测幽门螺杆菌结果。结果:治疗组和对照组1d的临床症状缓解率分别为80%、60%,差异有统计学意义(P<0.05);1周后症状缓解率均为98%。治疗组和对照组的溃疡愈合率分别为93%和76%,差异有统计学意义(P<0.05);治疗组和对照组的总有效率分别为98%和96%,差异无统计学意义(P>0.05)。治疗组和对照组的幽门螺杆菌根除率分别85%和81%,差异无统计学意义(P>0.05)。结论:两组方案均能有效治疗消化性溃疡和缓解临床症状,并能有效地根除幽门螺杆菌。但雷贝拉唑三联疗法在改善临床症状和促进溃疡愈合方面优于兰索拉唑三联疗法。     

Quadruple rescue therapy for Helicobacter pylori infection after two treatment failures

Background  A standard third-line therapy for Helicobacter pylori infection is lacking, and antimicrobial sensitivity data for patients who failed eradication therapy are often unavailable in clinical practice. We therefore designed the prospective study to assess the efficacy of levofloxacin, amoxicillin, bismuth and rabeprazole quadruple therapy as a third-line treatment for H. pylori infection.
Patients and methods  From September 2005 to August 2007, 37 consecutive H. pylori -infected patients who had failed standard first-line and second-line treatments underwent a 10-day quadruple therapy comprising rabeprazole (20 mg b.i.d.), bismuth subcitrate (300 mg q.d.s.), amoxicillin (500 mg q.d.s.) and levofloxacin (500 mg o.d.). Follow-up endoscopy with rapid urease test, histological examination and culture was performed at 6 weeks after the end of treatment to evaluate the response to therapy.
Results  Helicobacter pylori was successfully eradicated in 31 out of 37 patients (84% by both intention-to-treat analysis and per-protocol analysis). All patients complied with the eradication therapies, and only seven patients (19%) complained of mild-to-moderate adverse events. Amoxicillin- and levofloxacin-resistant strains were observed in 17% and 22% of the patients, respectively. There were no significant differences between H. pylori eradication rates and antibiotic resistances.
Conclusions  The 10-day levofloxacin- and amoxicillin-based quadruple therapy is well tolerated and achieves a high eradication rate as a third-line empirical treatment for H. pylori infection.     

The impact of primary antibiotic resistance on the efficacy of ranitidine bismuth citrate- vs. omeprazole-based one-week triple therapies in H. pylori eradication--a randomised controlled trial

AIMS: To compare ranitidine bismuth citrate with omeprazole as to their efficacy to eradicate H. pylori in two different treatment schedules both consisting of a combination of either of above with two antibiotics for 1 week, and to relate these treatment results to primary antibiotic resistance. METHODS: 256 H. pylori positive patients with non-ulcer dyspepsia were randomised to one of the following four treatment groups: omeprazole 20 mg + clarithromycin 500 mg + amoxycillin 1000 mg (OCA); ranitidine bismuth citrate 400 mg + clarithromycin 500 mg + amoxycillin 1000 mg (RBCCA); omeprazole 20 mg + clarithromycin 500 mg + metronidazole 500 mg (OCM); ranitidine bismuth citrate 400 mg + clarithromycin 500 mg + metronidazole 500 mg (RBCCM). All drugs were given twice daily for one week. The patients were assessed for prevalence of H. pylori by CLO test, histology and culture on gastric biopsy samples obtained during upper gastrointestinal endoscopy before randomisation and 4-6 weeks after completion of therapy. Bacterial sensitivity to clarithromycin, metronidazole and amoxycillin was determined by E-test. RESULTS: On per-protocol analysis, overall eradication rates were 96% for RBCCA vs. 85% for OCA (p = 0.03), and 95% for RBCCM vs. 79% for OCM (p = 0.01). Amongst the 196 patients (77% of the entire study group) in whom antibiotic sensitivity testing was technically feasible, primary resistance was found in 8% for clarithromycin, in 33% for metronidazole, and in 0% for amoxycillin. Eradication of clarithromycin sensitive/resistant strains was 89%/40% for OCA (p = 0.0042) and 98%/80% for RBCCA (p = 0.0428). When strains were sensitive to both antibiotics, cure rates with OCM/RBCCM were 87%/96% respectively (p = 0.39), for strains resistant to clarithromycin only, eradication was achieved in 82% with OCM vs. 94% with RBCCM (p = 0.2), and in the case of metronidazole resistance in 85% with OCM vs. 94% with RBCCM (p = 0.09). CONCLUSIONS: Ranitidine bismuth citrate in combination with clarithromycin and either metronidazole or amoxycillin produced higher eradication rates than omeprazole co-administered with the same antibiotics. This appeared especially prominent in the subgroups with clarithromycin resistance without, however, reaching statistical significance. Efficacy of neither eradication regimen was influenced by metronidazole sensitivity to a significant degree.