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Recent observations suggest an involvement of mast cells in Helicobacter pylori gastritis, but the mechanism of intraepithelial mast cell activation in H. pylori-infected patients remains to be clarified. Intraepithelial mast cells, identified by immunohistochemistry for CD117, were quantified in antral biopsies from 6 patients with H. pylori "active" chronic gastritis, 7 patients with H. pylori "nonactive" gastritis, and 9 controls. Antral biopsies from patients with H. pylori "active" gastritis showed higher intraepithelial mast cell counts than those from patients with H. pylori "nonactive" gastritis and from controls. Electron microscopy, selectively performed in 6 cases of H. pylori "active" gastritis, confirmed the presence of intraepithelial mast cells and allowed their subdivision into mature cells with intact electron-dense granules or degranulated cells. Other mast cells appeared to migrate through defects in the basement membrane into the epithelial layer. Mast cells in these areas often showed piecemeal degranulation or were characterized by large canaliculi, expanded Golgi areas, and a few granules, a process similar to the phase of recovery from anaphylactic degranulation of isolated human mast cells. The possible significance of these unusual ultrastructural findings is discussed.

Background & Aims: Helicobacter pylori attaches to gastric mucosa and grows as a biofilm. This constitutes protection from antimicrobial agents. We assessed the role of a pretreatment with n-acetylcysteine in destroying biofilm and overcoming H pylori antibiotic resistance., Methods: In an open-label, randomized controlled trial, 40 subjects with a history of at least 4 H pylori eradication failures were evaluated for biofilm presence, antibiotic susceptibility, and H pylori genotypes. Subjects were assigned randomly to receive (group A) or not (group B) n-acetylcysteine before a culture-guided antibiotic regimen. The primary end point was the H pylori eradication rate as assessed by (13)C-labeled urea breath testing., Results: H pylori was eradicated in 13 of 20 (both per-protocol and intention-to-treat analyses, 65%; 95% confidence interval, 44%-86%) group A participants and 4 of 20 (both per-protocol and intention-to-treat analyses, 20%; 95% confidence interval, 3%-37%) group B participants (P < .01). Biofilms persisted only in unsuccessfully treated participants. H pylori genotypes did not influence treatment outcome., Conclusions: N-acetylcysteine pretreatment before a culture-guided antibiotic regimen is effective in overcoming H pylori antibiotic resistance., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: We evaluated a new approach for the rapid detection of clarithromycin resistance in Helicobacter pylori, based on PCR and denaturing HPLC (DHPLC)., Methods: A 180 bp fragment of the 23S rRNA gene was amplified using DNA from 81 clinical H. pylori isolates (51 isolates were shown to be resistant to clarithromycin by Etest), and, directly, from 101 gastric biopsies from patients with digestive diseases, who were infected with H. pylori as assessed by a 13C-urea breath test, histology and/or culture. DHPLC was used to detect mutations in all the PCR products., Results: DHPLC profiles for the 30 susceptible isolates all showed homoduplex peaks; the resistant isolates consistently generated heteroduplex peaks that were easily distinguishable from the wild-type H. pylori reference strain. Sequencing revealed point mutations in all the resistant isolates. Overall, five different mutations were detected. Four of these mutations (A2142G, A2142C, A2143G and T2182C) are known to be associated with clarithromycin resistance; the remaining mutation (C2195T) has not been previously described. This novel single-base substitution was found in combination with the common mutation A2143G. Of the biopsies tested, 25 specimens generated heteroduplexes due to sequence alterations (mutation A2142G, A2142C or A2143G). In one of these specimens, A2143G was found together with the novel mutation T2221C; in another, a mixture of wild-type and mutant (A2143G) sequences was detected. For 20 culture-positive out of the 25 biopsies DHPLC results confirmed the presence of clarithromycin resistance., Conclusions: Our results suggest that the PCR-DHPLC assay is a valid tool for rapid assessment of clarithromycin resistance in H. pylori and that in the future it could be used directly on biopsy specimens, avoiding the need for culture-based methods.

Current treatment for Helicobacter pylori infections generally includes two or more antimicrobials (amoxicillin, clarithromycin, nitroimidazoles, tetracycline, etc.), but treatment fails in 10-20% of all cases, often because of drug resistance. Levofloxacin has been proposed as an alternative for these refractory infections. We examined 67 H. pylori isolates from patients unsuccessfully treated with amoxicillin, clarithromycin, metronidazole and levofloxacin. Minimum inhibitory concentrations determined with the epsilometer test revealed clarithromycin and metronidazole resistance in 91 and 82.1% of the isolates, respectively; 52 (77.6%) were resistant to both drugs. All 67 isolates were susceptible to amoxicillin and tetracycline. Fifty-two isolates had levofloxacin MICs of 0.01-2 mg/l; the remaining 15 (22.4%), all clarithromycin- and metronidazole-resistant, had MICs >/= 8 mg/l. Levofloxacin may be an option for refractory H. pylori infections, but the choice should be based on in vitro susceptibility data, and physicians should consider local resistance patterns when treating these infections empirically.

Background: Helicobacter pylori infection may persist after both first- and second-line current treatments., Aim: To assess the efficacy of a third-line, culture-guided treatment approach for the eradication of H. pylori., Methods: Patterns of resistance were analysed in H. pylori isolates from 94 consecutive patients in whom H. pylori infection had persisted after two eradication attempts. Using the epsilometer test, susceptibility analysis was performed for amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin. Patients were then treated with a culture-guided, third-line regimen: 89 patients with a 1-week quadruple regimen including omeprazole, bismuth, doxycycline and amoxicillin, and five patients with a 1-week triple regimen containing omeprazole, amoxicillin and levofloxacin or clarithromycin., Results: Ninety-four subjects (100%) were resistant to metronidazole, 89 (95%) to clarithromycin, 29 (31%) to levofloxacin and five (5%) to tetracycline. No resistance to amoxicillin was found in any patient. Overall, H. pylori eradication was obtained in 90% of subjects. The quadruple regimen was effective in 81 patients (92% by per protocol and 91% by intention-to-treat analysis). Four patients (80%, both per protocol and intention-to-treat analysis) were H. pylori-negative after the triple regimen., Conclusions: A culture-guided, third-line therapeutic approach is effective for the eradication of H. pylori. Furthermore, the 1-week doxycycline- and amoxicillin-based quadruple regimen is a good third-line 'rescue' treatment option.

Goals: To compare high-dose versus low-dose clarithromycin in 1-week triple therapy including rabeprazole and levofloxacin., Background: Regimens containing rabeprazole and levofloxacin have proved to be effective against H. pylori infection., Study: One-hundred H. pylori-positive patients were randomly assigned to one of the following 1-week regimens: rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and clarithromycin 250 mg b.d. (RLC-1 group); rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and clarithromycin 500 mg b.d. (RLC-2 group). H. pylori status was assessed at entry and after the treatment. Patients who experienced treatment failure underwent antibiotic susceptibility testing., Results: Forty-two patients in RLC-1 group (both PP and ITT analysis: 84%; 95%CI: 71-93%) and 47 in RLC2 group (both PP and ITT analysis: 94%; 95% CI: 83-98%) became H. pylori negative. Clarithromycin resistance was detected in all of 8 (100%) RLC-1 failures and in 1 out of 3 (33%) RLC-2 failures. Side effects occurred in 8% of patients in RLC-1 group and in 12% in RLC-2., Conclusions: Regimens tested are competitive with other PPI-based treatments. One-week triple therapy containing rabeprazole plus, levofloxacin, and high-dose clarithromycin yielded a higher eradicating rate than the one containing low-dose clarithromycin and may be considered as a first-line therapy option.

Background: Helicobacter pylori eradication therapies do not achieve 100% success rates. Antibiotic resistant strains are among the major causes of failure. Current recommendations concerning the management of treatment failures are not fully clear., Aim: To evaluate the efficacy of a multi-step therapeutic strategy in a large group of infected patients., Methods: A total of 2606 H. pylori-positive patients were administered tinidazole, clarithromycin and a proton pump inhibitor for 1 week. Patients with continuing infection were then given a second 1-week course of amoxycillin, clarithromycin and ranitidine bismuth citrate. Patients still infected after the second course underwent upper gastrointestinal endoscopy with H. pylori culture, and then received a 1-week quadruple proton pump inhibitor-bismuth based scheme established on H. pylori antibiotic sensitivity., Results: After the first step, eradication was achieved in 2063 out of 2413 patients [86% per protocol analysis (PP); 79% intention-to-treat analysis (ITT)]. First-step failures (350 out of 2413; 14.5% PP) showed second-step eradication rates of 82% (271 out of 329 patients, PP; 77% ITT). The specific quadruple therapy for second-step failures (58 out of 329, 18% PP) achieved 77% (30 out of 39 patients, PP) or 52% (ITT) success. This algorithm led to overall eradication rates of 99% (PP) or 91% (ITT)., Conclusions: This multi-step strategy succeeded in a high percentage of H. pylori infected patients. Given the lack of precise guidelines on treatment failures, assessing H. pylori sensitivity to antibiotics only after failure of the second treatment could be suggested in clinical practice.

Background/aims: Our study is to compare a short-term low-dose triple therapy with a long-term medium-dose double therapy for H.pylori eradication., Materials and Methods: One hundred and ten consecutive patients, suffering from dyspeptic symptoms, with H.pylori infection, were randomly allocated to one of the following 2 groups with different therapeutic regimens: A) omeprazole 20 mg/day for 7 days, tinidazole 500 mg bid for 7 days, clarithromycin 250 mg bid for 7 days (55 pts, 20 with peptic ulcer); B) omeprazole 20 mg bid for 14 days, amoxycillin 1000 mg bid for 14 days (55 pts, 28 with peptic ulcer). The "H.pylori status" was evaluated by means of histology, culture and urease test, at entry and 8 weeks after treatment., Results: Two group A and one group B pts didn't complete the treatment. The H.pylori eradication was obtained in 38 pts of group A (71.69%) (C.I.95%: 55.19176-80.86293), in 31 of group B (58.49%) (C.I.95%: 42.32777-69.7017); on Intention-to-Treat analysis, the rate of eradication gave similar results. Side effects occurred in 9 pts of group A (16.98%), in 8 of group B (14.81%)., Conclusions: Short-term low-dose triple therapy with omeprazole/tinidazole/clarithromycin has a better cost/benefit ratio than long-term dual therapy with omeprazole/amoxycillin in the H.pylori eradication, but it causes more side-effects.

Background: The aim of our study was to compare two 1-week, low-dose triple therapies for Helicobacter pylori eradication., Methods: One hundred consecutive patients, suffering from dyspeptic symptoms with H. pylori infection, were randomly allocated to 7 days of treatment with omeprazole 20 mg o.m. plus clarithromycin 250 mg b.d. and either tinidazole 500 mg b.d. (group A: n = 50, 19 with peptic ulcer) or amoxycillin 1000 mg b.d. (group B: n = 50, 20 with peptic ulcer). H. pylori-status was evaluated by means of histology, culture and urease test, at entry and 8 weeks after treatment., Results: Three patients did not complete the treatment. H. pylori eradication was obtained in 35 patients from group A (73%) (95% CI, 55-82%) and in 40 patients from group B (82%) (95% CI, 66-90%). On intention-to-treat analysis, the rates of eradication were similar. Side-effects occurred in seven patients from group A (14.58%) and in four patients from group B (8.33%), but none discontinued therapy because of side-effects., Conclusion: Both triple 1-week, low-dose omeprazole therapies gave good eradication rates with infrequent side-effects.

Mucosa-associated lymphoid tissue (MALT) showing a follicular structure can develop in the gastric mucosa as a response to Helicobacter pylori infection. We emphasize the importance of anti-H. pylori antibiotic therapy in the elimination of acquired MALT. Of the 200 patients studied, acquired MALT was found in 70 of the 151 H. pylori-positive patients, whereas it was present in only five of the 49 H. pylori-negative patients. Thirty-eight H. pylori-positive and MALT-positive patients were treated with antibiotic therapy and reevaluated after 6 months: 21 patients were H. pylori negative/MALT negative, 12 were H. pylori positive/MALT positive, four were H. pylori negative/MALT positive, one was H. pylori positive/MALT negative. In the control group (n = 20), H. pylori and acquired MALT were still present at follow-up. One patient with histological and immunohistochemical evidence of low-grade B-cell gastric MALT lymphoma underwent antibiotic treatment and was reexamined after 8, 12, and 24 weeks: histological examination of biopsy samples showed regression of the MALT lymphoma in tandem with the disappearance of H. pylori colonization. Our data confirm the correlation between H. pylori infection and acquired MALT, as documented by the ability of antibiotic therapy to induce the disappearance of acquired MALT and regression of MALT lymphoma. Considering the potential evolution of MALT into low-grade B-cell MALT lymphoma, H. pylori eradication should play a role in the prevention of this tumor.