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138 Helicobacter pylori Eradication with Either Conventional 10-Day Triple Therapy or 10-Day Modified Sequential Regimen. (Preliminary Report)
antibody, and reduced the bacterial burden in spleen and MLNs. Conclusion: GM-CSF plays an important role in host mucosal defense to enteric pathogens, which is mediated, in part, via its activity on host DCs. Supported by NIH grant DK35108.
bid + amoxicillin 1g bid for five days, followed Omeprazole 20mg bid + clarithromycin 500 mg bid + Metronidazole 500 mg bid for another five days). Fifteen days after completion of therapy, eradication was assessed by a fecal antigen test. Results were statistically compared. Results: One hundred fifty-eight patients were enrolled. Eighty-two patients were assigned to the conventional therapy group and seventy-six patients received modified sequential therapy. Both populations were similar. Conventional therapy resulted in 87.8% eradication rate, while sequential therapy achieved 85.5% (p=0.67). There was no statistically significant difference between both groups in terms of adverse effects, except for nausea, which was reported higher in the sequential therapy group (p=0.03). Conclusions: In Helicobacter pyloriinfected patients, a modified sequential therapy is as effective as conventional triple therapy in achieving eradication. Given the fact that sequential therapy is cheaper than conventional triple therapy, it represents a good alternative of treatment.
AGA Abstracts
136b Enhanced Dendritic Cell (DC) Maturation and Retention in Crohn's Disease Mucosa: Possible Role in Potentiating T Cell Responses to Enteric Bacteria Ernesto R. Drelichman, Lea Novak, Ronald H. Clements, Devin E. Eckhoff, Lois Musgrove, Meg Mosteller-Barnum, Phillip D. Smith, Lesley E. Smythies Background: Intestinal dendritic cell (DC) regulation of human mucosal immunity has received little investigative attention compared to that of intestinal macrophages (Smythies, et al. J. Clin. Invest. 2005). Therefore, we sought to identify and characterize human intestinal DCs that sample, migrate and deliver apically applied antigen to autologous T cells. Methods: Explants of normal intestinal mucosa from healthy subjects and non-inflamed mucosa from patients with Crohn's disease (Crohn's mucosa) were placed in a transwell system and inert material or antigen was inoculated onto the apical surface. After exposure to FITC-labeled latex beads, GFP-labeled S. typhimurium, E. coli or CBir protein from Crohn's associated bacteria, the explanted tissue was sectioned, stained for epithelial tight junction proteins, DC markers and anti-GFP antibodies, and examined by confocal microscopy. Cells that migrated through the mucosa were phenotyped for CD11b, CD11c and CD83 and tested for the ability to induce bacteria-specific T cell proliferation. Results: Confocal microscopy revealed that epithelial cell tight junction integrity was maintained for 120 min following the application of inert material or non-invasive Salmonella, but lost by 60 min following the application of invasive Salmonella. DCs in normal mucosa rapidly took up cargo, migrated and exited the mucosa within 15-60 min in a time- and temperature-dependent manner. In contrast, DCs in Crohn's mucosa took up cargo but migrated less effectively, remaining largely within the tissue. 12.2% of migrated cells at 60 min expressed CD83, the marker of DC maturity, compared to 1.2% of migrated cells from mock-inoculated mucosa, indicating that antigenic stimulation of the mucosa induces DC migration. The DCs that took up inert cargo were CD11c-/CD11b+, whereas DCs that took up bacterial cargo were CD11c+/ CD11b+, suggesting separate DC subsets take up different types of cargo. Importantly, the DCs that took up bacteria, but not FITC-beads, and migrated from the mucosa potently supported autologous T cell proliferation. Conclusions: Antigen applied to the apical surface of normal mucosa promotes rapid mucosal DC migration, maturation and bacteria-specific antigen presentation. In contrast, migration of DCs from Crohn's mucosa is delayed, leading to retention of pulsed DCs in the lamina propria and offering a possible explanation for the greater prevalence of DCs in Crohn's disease mucosa. These findings suggest that DCs in the intestinal mucosa of patients with Crohn's disease likely potentiate T cell responses to enteric bacteria.
139 A Single Urea Breath Test At 4 Weeks Is As Effective As Two Sequential Breath Tests At 4 and 8 Weeks in Determining the Success of Eradication Therapy for Helicobacter pylori (H Pylori) : An Analysis of 454 Patients Nimish Vakil, Angelo Zullo, Chiara Ricci, Cesare Hassan, Dino Vaira Background: Current standards for determining if eradication of H pylori has taken place after treatment require a combination of endoscopic tests or two breath tests taken 4 weeks apart, to be negative. Aim: To determine the accuracy of a single 13C urea breath test 4 weeks after completion of therapy to the results of two 13C UBTs taken at 4 and 8 weeks after treatment. Methods: All infected patients who participated in randomized controlled trials of H pylori eradication were studied. All patients had a urea breath test before receiving H pylori eradication therapy and a 13C UBT was obtained 4 weeks and 8 weeks after therapy as recommended by regulatory guidelines and the recommendations of the European H Pylori study group. Results: Overall, 454 patients with H pylori infection who participated in different randomized controlled trials of H pylori eradication were evaluated. There were 184 males and the mean age was 51+14. The endoscopic diagnosis were: antral gastritis: 341, Duodenal ulcer 20; gastric ulcer 5; oesophagitis 88. The delta over baseline (DOB) value before treatment was 44+27 ppm. The different treatments in the trial were: Sequential therapy =234, Triple therapy=197 and Levofloxacin triple therapy =23. Following treatment, the mean DOB in patients who had a successful cure was 0.72+2 ppm at 1 month & was similar to the value at 2 months (0.7+1.7; ns). In patients who remained infected, the mean DOB at 4 weeks was 30+31 ppm 1 month after therapy was completed and 46+28 at 8 weeks. There was only one discordant result. One patient with a positive UBT at week 4 was negative at week 8. No negative breath test at week 4, became positive at week 8. At a cost of $110 a breath test, the incremental cost of performing two breath tests would be $47,740 for a single case re-classified after the second breath test. Conclusions: 1. A single urea breath test, 4 weeks after treatment is as effective as two serial breath tests (at 4 and 8 weeks after treatment) in determining if H pylori eradication. 2. The incremental cost of the second breath test ($47,740/mis-classification prevented) is prohibitive. 3. A single UBT under-estimates the efficacy of therapy rather than over-estimate it.
137 Randomized Controlled Comparison of Sequential and Quadruple (Concomitant) Therapies for H. pylori Infection Deng-Chyang Wu, Ping-I Hsu, Jeng-Yih Wu, Antone R. Opekun, David Y. Graham
140
Background: Sequential therapy has repeatedly been shown to be superior to legacy triple therapy (PPI, amoxicillin, clarithromycin) but used different triple therapy components in the triple portion of the sequential therapy (ie, PPI, clarithromycin, tinidazole). We compared sequential and quadruple therapy both containing the legacy triple therapy components (a PPI plus 3 antibiotics: amoxicillin, clarithromycin, and metronidazole) for H. pylori eradication. Methods: This was a multi-center randomized comparison of two methods of providing the components of the legacy triple therapies. The study was done in three medical centers in Taiwan. H. pylori-infected patients were randomly assigned receive twice-a-day therapy with 40 mg esomeprazole, 1 g amoxicillin, 500 mg clarithromycin, and 500 mg metronidazole. The drugs were given as a sequential therapy with an initial 5 days of PPI plus amoxicillin followed the 5 days of the PPI plus clarithromycin and metronidazole (total 10 days) or as a concomitant quadruple therapy where all 4 drugs (the PPI plus the 3 antibiotics) were given twice a day for 7 days. Pretreatment H pylori status required positive rapid urease test and histology. Eradication was assessed 8 weeks after the end of treatment by rapid urease and histology or by the urea breath test. Results: 129 patients ranging in age from 24 to 81 years (M:F = 1.6:1) have completed therapy. Intention to treat eradication rates were similar for sequential and quadruple therapies (ie, 89% [59/66] vs. 87% [55/63], respectively). Per-protocol cure rates were also similar: 93% [56/60] vs. 91% [52/57], respectively. The frequencies of adverse events were also similar (12% [8/66] vs. 16% [10/ 63]) as was drug compliance (94% [62/66] vs. 94% [59/63]). Conclusions: Sequential and concomitant administration of the same drugs provides similar results. The sequential administration protocol may produce unnecessary complexity for both patients and physicians compared to prescribing all the medications (concomitant administration) from the outset.
Effect of Three Different Regimens with Esomeprazole, Amoxicillin, and Moxifloxacin in the Treatment of Primary H. pylori Infection Flora Sacco, Mariangela Spezzaferro, Mariaelena Serio, Maria Amitrano, Brunella Cerasa, Laurino Grossi, Leonardo Marzio Introduction: In previous studies we have shown that primary resistance of H. pylori to fluoroquinolones in our geographic region is between 8 to 12% of strains collected from patients never treated in their past for H. pylori infection and that a triple therapy with fluoroquinolones may be highly efficacious in the treatment of H. pylori infection. The optimum dosage and duration of the treatment however, has not been assessed yet and data from the literature about this issue are discordant. Aim: to evaluate the therapeutic efficacy of an association of moxifloxacin, amoxicillin and esomeprazole in three different regimens in patients with primary H. pylori infection. Methods and patients: patients with H. pylori infection as diagnosed either with Urea Breath test (UBT) or with CP test during upper g.i. endoscopy were randomly assigned to one of the following triple therapies: esomeprazole 20 mg b.i.d., amoxicillin 1gr b.i.d., moxifloxacin 400 mg o.i.d for 10 days (EAM400x10); esomeprazole 20 mg b.i.d., amoxicillin 1gr b.i.d., moxifloxacin 400 mg b.i.d for 5 days (EAM800x5); esomeprazole 20 mg b.i.d., amoxicillin 1gr b.i.d., moxifloxacin 400 mg b.i.d. for 10 days (EAM800x10). Eradication success was assessed with UBT two months after the end of treatment and Per Protocol (PP) in which only data from adherent subjects are analysed, and Intention-To-Treat (ITT) in which all subjects are followed regardless of adherence, were calculated. Results: So far 41,36 and 43 patients has been recruited in group EAM400x10, EAM800x5, and EAM800x10 respectively. One patient in EAM400x10 group ,2 patients in EAM800x5 group, and 1 patient in the EAM800x10 group did not return for control. Eradication rate in each group is described in the table. Conclusion: Triple therapy with esomeprazole 40mg/day, amoxicillin 2g/day and moxifloxacin 800 mg/ day for 10 days is more efficacious than the same treatment for 5 days and a treatment with esomeprazole 40 mg/day, amoxicillin 2g/day and moxifloxacin 400 mg/day for 10 days in the eradication of primary H. pylori infection.
138 Helicobacter pylori Eradication with Either Conventional 10-Day Triple Therapy or 10-Day Modified Sequential Regimen. (Preliminary Report) Jose R. Ruiz-Obaldía, Euriko G. Torrazza, Norberto O. Carreno Background: Helicobacter pylori eradication rates with sequential therapy (proton pump inhibitor bid + amoxicillin bid for five days, followed by proton pump inhibitor bid + clarithromycin bid + tinidazole bid for another five days) have been reported superior to those achieved with conventional triple therapy (proton pump inhibitor bid + amoxicillin bid + clarithromycin bid). Objective: We evaluated the effect of a modified sequential therapy (using Metronidazole bid instead of tinidazole) as compared with conventional triple therapy. Methods: Patients with biopsy-proven Helicobacter pylori infection were randomly assigned to receive either conventional triple therapy (Omeprazole 20mg bid + amoxicillin 1g bid + clarithromycin 500mg bid for ten days) or a modified sequential therapy (Omeprazole 20mg
AGA Abstracts
P<0.02 vs EAM400x10(χ2)
A-24
bid + amoxicillin 1g bid for five days, followed Omeprazole 20mg bid + clarithromycin 500 mg bid + Metronidazole 500 mg bid for another five days). Fifteen days after completion of therapy, eradication was assessed by a fecal antigen test. Results were statistically compared. Results: One hundred fifty-eight patients were enrolled. Eighty-two patients were assigned to the conventional therapy group and seventy-six patients received modified sequential therapy. Both populations were similar. Conventional therapy resulted in 87.8% eradication rate, while sequential therapy achieved 85.5% (p=0.67). There was no statistically significant difference between both groups in terms of adverse effects, except for nausea, which was reported higher in the sequential therapy group (p=0.03). Conclusions: In Helicobacter pyloriinfected patients, a modified sequential therapy is as effective as conventional triple therapy in achieving eradication. Given the fact that sequential therapy is cheaper than conventional triple therapy, it represents a good alternative of treatment.
AGA Abstracts
136b Enhanced Dendritic Cell (DC) Maturation and Retention in Crohn's Disease Mucosa: Possible Role in Potentiating T Cell Responses to Enteric Bacteria Ernesto R. Drelichman, Lea Novak, Ronald H. Clements, Devin E. Eckhoff, Lois Musgrove, Meg Mosteller-Barnum, Phillip D. Smith, Lesley E. Smythies Background: Intestinal dendritic cell (DC) regulation of human mucosal immunity has received little investigative attention compared to that of intestinal macrophages (Smythies, et al. J. Clin. Invest. 2005). Therefore, we sought to identify and characterize human intestinal DCs that sample, migrate and deliver apically applied antigen to autologous T cells. Methods: Explants of normal intestinal mucosa from healthy subjects and non-inflamed mucosa from patients with Crohn's disease (Crohn's mucosa) were placed in a transwell system and inert material or antigen was inoculated onto the apical surface. After exposure to FITC-labeled latex beads, GFP-labeled S. typhimurium, E. coli or CBir protein from Crohn's associated bacteria, the explanted tissue was sectioned, stained for epithelial tight junction proteins, DC markers and anti-GFP antibodies, and examined by confocal microscopy. Cells that migrated through the mucosa were phenotyped for CD11b, CD11c and CD83 and tested for the ability to induce bacteria-specific T cell proliferation. Results: Confocal microscopy revealed that epithelial cell tight junction integrity was maintained for 120 min following the application of inert material or non-invasive Salmonella, but lost by 60 min following the application of invasive Salmonella. DCs in normal mucosa rapidly took up cargo, migrated and exited the mucosa within 15-60 min in a time- and temperature-dependent manner. In contrast, DCs in Crohn's mucosa took up cargo but migrated less effectively, remaining largely within the tissue. 12.2% of migrated cells at 60 min expressed CD83, the marker of DC maturity, compared to 1.2% of migrated cells from mock-inoculated mucosa, indicating that antigenic stimulation of the mucosa induces DC migration. The DCs that took up inert cargo were CD11c-/CD11b+, whereas DCs that took up bacterial cargo were CD11c+/ CD11b+, suggesting separate DC subsets take up different types of cargo. Importantly, the DCs that took up bacteria, but not FITC-beads, and migrated from the mucosa potently supported autologous T cell proliferation. Conclusions: Antigen applied to the apical surface of normal mucosa promotes rapid mucosal DC migration, maturation and bacteria-specific antigen presentation. In contrast, migration of DCs from Crohn's mucosa is delayed, leading to retention of pulsed DCs in the lamina propria and offering a possible explanation for the greater prevalence of DCs in Crohn's disease mucosa. These findings suggest that DCs in the intestinal mucosa of patients with Crohn's disease likely potentiate T cell responses to enteric bacteria.
139 A Single Urea Breath Test At 4 Weeks Is As Effective As Two Sequential Breath Tests At 4 and 8 Weeks in Determining the Success of Eradication Therapy for Helicobacter pylori (H Pylori) : An Analysis of 454 Patients Nimish Vakil, Angelo Zullo, Chiara Ricci, Cesare Hassan, Dino Vaira Background: Current standards for determining if eradication of H pylori has taken place after treatment require a combination of endoscopic tests or two breath tests taken 4 weeks apart, to be negative. Aim: To determine the accuracy of a single 13C urea breath test 4 weeks after completion of therapy to the results of two 13C UBTs taken at 4 and 8 weeks after treatment. Methods: All infected patients who participated in randomized controlled trials of H pylori eradication were studied. All patients had a urea breath test before receiving H pylori eradication therapy and a 13C UBT was obtained 4 weeks and 8 weeks after therapy as recommended by regulatory guidelines and the recommendations of the European H Pylori study group. Results: Overall, 454 patients with H pylori infection who participated in different randomized controlled trials of H pylori eradication were evaluated. There were 184 males and the mean age was 51+14. The endoscopic diagnosis were: antral gastritis: 341, Duodenal ulcer 20; gastric ulcer 5; oesophagitis 88. The delta over baseline (DOB) value before treatment was 44+27 ppm. The different treatments in the trial were: Sequential therapy =234, Triple therapy=197 and Levofloxacin triple therapy =23. Following treatment, the mean DOB in patients who had a successful cure was 0.72+2 ppm at 1 month & was similar to the value at 2 months (0.7+1.7; ns). In patients who remained infected, the mean DOB at 4 weeks was 30+31 ppm 1 month after therapy was completed and 46+28 at 8 weeks. There was only one discordant result. One patient with a positive UBT at week 4 was negative at week 8. No negative breath test at week 4, became positive at week 8. At a cost of $110 a breath test, the incremental cost of performing two breath tests would be $47,740 for a single case re-classified after the second breath test. Conclusions: 1. A single urea breath test, 4 weeks after treatment is as effective as two serial breath tests (at 4 and 8 weeks after treatment) in determining if H pylori eradication. 2. The incremental cost of the second breath test ($47,740/mis-classification prevented) is prohibitive. 3. A single UBT under-estimates the efficacy of therapy rather than over-estimate it.
137 Randomized Controlled Comparison of Sequential and Quadruple (Concomitant) Therapies for H. pylori Infection Deng-Chyang Wu, Ping-I Hsu, Jeng-Yih Wu, Antone R. Opekun, David Y. Graham
140
Background: Sequential therapy has repeatedly been shown to be superior to legacy triple therapy (PPI, amoxicillin, clarithromycin) but used different triple therapy components in the triple portion of the sequential therapy (ie, PPI, clarithromycin, tinidazole). We compared sequential and quadruple therapy both containing the legacy triple therapy components (a PPI plus 3 antibiotics: amoxicillin, clarithromycin, and metronidazole) for H. pylori eradication. Methods: This was a multi-center randomized comparison of two methods of providing the components of the legacy triple therapies. The study was done in three medical centers in Taiwan. H. pylori-infected patients were randomly assigned receive twice-a-day therapy with 40 mg esomeprazole, 1 g amoxicillin, 500 mg clarithromycin, and 500 mg metronidazole. The drugs were given as a sequential therapy with an initial 5 days of PPI plus amoxicillin followed the 5 days of the PPI plus clarithromycin and metronidazole (total 10 days) or as a concomitant quadruple therapy where all 4 drugs (the PPI plus the 3 antibiotics) were given twice a day for 7 days. Pretreatment H pylori status required positive rapid urease test and histology. Eradication was assessed 8 weeks after the end of treatment by rapid urease and histology or by the urea breath test. Results: 129 patients ranging in age from 24 to 81 years (M:F = 1.6:1) have completed therapy. Intention to treat eradication rates were similar for sequential and quadruple therapies (ie, 89% [59/66] vs. 87% [55/63], respectively). Per-protocol cure rates were also similar: 93% [56/60] vs. 91% [52/57], respectively. The frequencies of adverse events were also similar (12% [8/66] vs. 16% [10/ 63]) as was drug compliance (94% [62/66] vs. 94% [59/63]). Conclusions: Sequential and concomitant administration of the same drugs provides similar results. The sequential administration protocol may produce unnecessary complexity for both patients and physicians compared to prescribing all the medications (concomitant administration) from the outset.
Effect of Three Different Regimens with Esomeprazole, Amoxicillin, and Moxifloxacin in the Treatment of Primary H. pylori Infection Flora Sacco, Mariangela Spezzaferro, Mariaelena Serio, Maria Amitrano, Brunella Cerasa, Laurino Grossi, Leonardo Marzio Introduction: In previous studies we have shown that primary resistance of H. pylori to fluoroquinolones in our geographic region is between 8 to 12% of strains collected from patients never treated in their past for H. pylori infection and that a triple therapy with fluoroquinolones may be highly efficacious in the treatment of H. pylori infection. The optimum dosage and duration of the treatment however, has not been assessed yet and data from the literature about this issue are discordant. Aim: to evaluate the therapeutic efficacy of an association of moxifloxacin, amoxicillin and esomeprazole in three different regimens in patients with primary H. pylori infection. Methods and patients: patients with H. pylori infection as diagnosed either with Urea Breath test (UBT) or with CP test during upper g.i. endoscopy were randomly assigned to one of the following triple therapies: esomeprazole 20 mg b.i.d., amoxicillin 1gr b.i.d., moxifloxacin 400 mg o.i.d for 10 days (EAM400x10); esomeprazole 20 mg b.i.d., amoxicillin 1gr b.i.d., moxifloxacin 400 mg b.i.d for 5 days (EAM800x5); esomeprazole 20 mg b.i.d., amoxicillin 1gr b.i.d., moxifloxacin 400 mg b.i.d. for 10 days (EAM800x10). Eradication success was assessed with UBT two months after the end of treatment and Per Protocol (PP) in which only data from adherent subjects are analysed, and Intention-To-Treat (ITT) in which all subjects are followed regardless of adherence, were calculated. Results: So far 41,36 and 43 patients has been recruited in group EAM400x10, EAM800x5, and EAM800x10 respectively. One patient in EAM400x10 group ,2 patients in EAM800x5 group, and 1 patient in the EAM800x10 group did not return for control. Eradication rate in each group is described in the table. Conclusion: Triple therapy with esomeprazole 40mg/day, amoxicillin 2g/day and moxifloxacin 800 mg/ day for 10 days is more efficacious than the same treatment for 5 days and a treatment with esomeprazole 40 mg/day, amoxicillin 2g/day and moxifloxacin 400 mg/day for 10 days in the eradication of primary H. pylori infection.
138 Helicobacter pylori Eradication with Either Conventional 10-Day Triple Therapy or 10-Day Modified Sequential Regimen. (Preliminary Report) Jose R. Ruiz-Obaldía, Euriko G. Torrazza, Norberto O. Carreno Background: Helicobacter pylori eradication rates with sequential therapy (proton pump inhibitor bid + amoxicillin bid for five days, followed by proton pump inhibitor bid + clarithromycin bid + tinidazole bid for another five days) have been reported superior to those achieved with conventional triple therapy (proton pump inhibitor bid + amoxicillin bid + clarithromycin bid). Objective: We evaluated the effect of a modified sequential therapy (using Metronidazole bid instead of tinidazole) as compared with conventional triple therapy. Methods: Patients with biopsy-proven Helicobacter pylori infection were randomly assigned to receive either conventional triple therapy (Omeprazole 20mg bid + amoxicillin 1g bid + clarithromycin 500mg bid for ten days) or a modified sequential therapy (Omeprazole 20mg
AGA Abstracts
P<0.02 vs EAM400x10(χ2)
A-24