- Email: [email protected]
Amoxycillin and ampicillin are not transfered to gastric juice irrespective of Helicobacter pylori status or acid blockade by omeprazole
2989
inflammation scores pre-treatment and no acute inflammation post-treatment. Conclusions Contrary to expectations, Helicobactergastritis did not significantly increase gastric antibiotic transfer. This may be due to the large inter-subject variability in gastric antibiotic secretion rates, which limits the usefulness of human experiments for examining gastric antibiotic secretion mechanisms.
Amoxycillin and Ampicillin Are Not Transtnred to Gastric Juice irrespective of Hollcobacfer pylori Status or Acid Blockade by Omeprazole Rodrigo M. Ortiz, Luiz R. Abreu, Silvana A. Callatatti, Andreia Cora77a,Maristela Deguer, Patricia Marques, Jos Pedrazzoli, USF, Braganca Pta Brazil
Gastricclearanceof antibiotics(mL/min) Ar~ibioUc
Amoxicillin
Clarithromycin
Melrontdazole
H, py/or/.ve volunteers H. py/or/+ve patients H. pylori -ve patients post.treatment
0.270 _+0.205 0.434 _+0,418
6.61 ± 2.82 5,66 ± 6 14
'1.85± 1.03 t.76 ± 0.76
0.362 + 0,361
10.10± 7 70
Background and aims: The effect of proton pum inhibitors and Hp infection on distribution of drugs employed for the eradication of this bacteria are poorly understood. The aim of this study was to investigate the effect of a 7-day administration of 20 mg omeprazole on the pharmacokinetics of amoxycillin and ampicillin in the palsma, saliva and gastric juice of individuals with and without Hp infection. Methods: 53 healthy volunteers without endoscopic lesions were enrolled. 24 volunteers were included in the amoxycillin study and 29 individuals in the ampicillin study. Each one has an open randomized two-period crossover design and a 21-day washout period between phases. Plasma, saliva and gastric juice concentrations of amoxycillin and ampicillin in subjects with and without omeprazole pre-treatment and with and without Hpinfection were measured by reversed-phaseHPLCwith ultraviolet detection.Results: Neither pre-treatment with pmeprazole nor Hp infection interfered with the plasma bioavailability as assessed by AUC~. Neither ampicillin were detected in saliva or gastric juice at any study phase. Conclusion: Short-term treatment with omperazole do not interfere with the pharmacokinetics of amoxycillin or ampicillin. Our results alsos exclude the presence of a transfer mechanism for amoxycillin or ampicillin from plasma to gastric juice.
2987 Clarithromycin MICs Level Against Helicobacter pylod (Hp) in Pro and Post Treatment Luigi Gatta, Dept of internal Medicine and Gastroenterology, Bologna Italy; Natale Figura, GI Unit, Siena Italy; Chiara Ricci, Dept of Internal Medicine and Gastroenterology, Bologna Italy; Luigi D'Anna, Military Hosp, Rome Italy; Marcello Menagatti, Federico Perna, Sonla Berardi, Andrea Tampieri, Dept of Internal Medicine and Gastroenterology, Bologna Italy; John Holton, Microbiology, UCL, London United Kingdom; Mario Miglioli, Dino Vaira, Dept of Internal Medicine and Gastroenterology, Bologna Italy
299O Cure of H./w/or/IntecUon Does Not Reduce COX-2 and Nitrntyrosine Expression in Gastric Mucoso with Intestinal Mntaplasia. Arats Kimura, Shiogo Tsuji, Masahiko Tsujii, Naoki Kawai, Masakazu Yasumaru, Yoshimi Kakiuchi, Yutska Sasaki, Masatsugu Hurt, Dept of Internal Medicine and Therapeutics, Soita City Japan; Sunao Kawano, Dept of C/in Lab Science, Sch of Allied
Aim: a) to evaluate the rate of susceptibility (S) to clarithromycin (C) in Hp strains isolated in our geographic area from patients nevertreated for Hp; b) to assessthe impact of resistance (R) and different levels of S to C on the treatment (ix) outcome; c) to determine secondary R rate and MICs value variations of C before and after 1~. Methods: over a 25 months period, 535 Hp strains were isolated from consecutive patients (M/F = 277/258; age range 18-86 yrs; mean age 50 yrs). S was assessed by E-test: C-R it MICgowas > 21g/ml. 457 (M/F=245/ 212; age range 18-84yrs; mean age 50 yrs) out of 535 HP patients were treated with PPI od + amoxicillin 1 g bd + C 500 mg bd for 7 days and 426 C MICs values were available. So far 174 (M/F = 105/69; age range 20-82yrs; mean age 50 yrs) out of 457 underwent endoscopy follow-up four weeks after stopping tx with re-evaluation of C-MICs if still Hp positive. Results: 92/426 (21%) were C-resistant and no significance differences were found according to gender (p>O,05). MICso75and ~ of C were 0,032, 0,094 and 64pg/ml respectively. The overall ratio of eradication in the 174 patients were 73% (n = 127). The one observed in 17 patients with C-resistant strains was 35,2% (6/17). The eradications in relation to the MICso ~ and ~ of C were 76%, 77% and 70% respectively. 34/47 cultures from not eradicated patients were obtained. The ratio of secondary resistant to C was 36% (9/25). We were also able to compare the pre and post b< MIC value for 18 strains. Post-tx MICs values of C for S strains that were still S after unsuccessful tx were the same only in 4 cases. In the other 6 S strains post-tx MICs were increased by 2-5 times. 6 strains became R to quite high levels. Conclusions: Our results suggest not to use C after unsuccessful treatment, even in cases in which strains are still susceptible.
Background and Aim: Accumulating body of evidence reveals that H. pylori(Hp) infection is a risk factor for gastric carcinogenesis, however, the mechanism for Helicobacter-related gastric carcinogenesis is unclear. Recent studies have demonstrated that cyciooxygenase 2 (COX-2) and nitric oxide (NO) have an important role for gastric carcinogenesis. However, the effects of Hp eradicafion on COX-2expression and NO production have not beenelucidated. The present study investigated the distribution of COX-2 and nitrotyrosine, a biologic marker for NO-related compounds in human gastric mucosa immunohistochemically and evaluated the expression before and after successful eradication of Hp infection in gastric mucosa with/ without intestinal metaplasia(IM), which is hypothesized to be a precancerous lesion of intestinal type of gastric cancer. Subjects and Methods: After informed consent was obtained, antral biopsy specimens were obtained from eight subjects(49.6 -+ 20.5 y)before and after eradication ofl-lp.lmmunohistochemical staining of COX-2/nitrotyrosine was performed and positive staining of COX-2/nitrotyrosine in the epithelium was expressed as the percentage of stained cells to the total epithelial cells The histoiogic status of the gastric mucosa was scored according to the updated Sydney system. Results: Graded variables except IM were significantly decreased after successful eradication of Hp (p
2988 Synergy Study of Rabeprazole in Combinationwith Mstrontdazole or Cladlkromycin Against Sensitive and Resistant Clinical H. pylor/Isolates. Andreas Mentis, Hellenic Pasteur Institute, Athens Greece; Theodore Rokkas, Henry Dunant Hosp, Athens Greece Rabeprazole (RAB), is a new proton pump inhibitor (PPI) and few in vitro data exist on its interaction with antibiotics commonly used for the treatment of H. pylori infection. Aim: To study the in vitro synergy of RAB and the antibiotics metronidazole (MET) or clarithromycin (CLA) against recently isolated clinical H. pylori strains exhibiting susceptibility or resistance to these antibiotics. Material and methods: The agar dilution chequerboard and the killing curve methods were employed. Twenty one H. pyloriclinical isolates and one reference strain were used in the chequerboard method. Eleven strains were susceptible to both antibiotics, whereas, ten were resistant to one or both antibiotics. The in vitro synergy was evaluated by the fractional inhibitory concentration (FIC) for each combination. Killing curves were constructed for RAB, MET and CLA individually and in combination at 0,5x, lx, and 2x MIC. The number of viable colonies was counted at 0,2,6,12, and 24h. Synergy with each combination was defined as a > 21og10reduction of CFU/mL compared with the most active agent alone. An agent was considered bactericidal if it produced a > 3 IoglO cfu/mL decrease from the initial inoculum. Results: In the chequerboard method, the minimum FIC ranged from 0,5 to 125 and the maximum FIC from 0,75 to 1,75. Synergy of the combination of MET and RAB as defined by an FICmin < 0.5 and partial synergy (FICmin between 0.5 and 1) was observed against one out of 10 strains exhibiting resistance to either MET / CLA or both antibiotics, and against 5 out of 11 sensitive H. pylori isolates. Synergy of the combination of CLA and RAB and partial synergy was observed against 3 out of 10 resistant, and against 6 out of 11 sensitive H. pylori isolates. In the time-kill assay, the combination of MET and RAB was synergistic against one, whereas the combination of CLA and RAB against three isolates. Synergistic effects were observed only when the strains were sensitive to both of the antibiotics investigated. Bactericidal effect was found against three isolates. No antagonism of any combination of RAB and the antibiotics was observed in any of the two methods. Conclusions. The combination of RAB with antibiotics was synergistic against a considerable number of /-/. py/ori strains. RAB plus CLA combination was synergistic (partially or totally) in a higher percentage of isolates compared to the RAB plus MET combination. This interaction was more profound against isolates sensitive to both antibiotics.
Effect of Helicobacler pylori Eradication on Epithelial Cell Turnover and p53 Expression of the Gastric Mucoso in Patients with Chronic Gastritis -Comparison Between Intestinal Mntaplastic and Non-Mntaplastic Mocosa Ryogo Sato, Toshio Fujioka, Kazunari Murakami, Masaaki Kodama, Tadayoshi Okimoto, Masaru Nasu, Oita Medical Univ, Oita Japan Background and aims: Some papers have indicated that epithelial cell turnover and p53 expression were acceleratedand eradication of Helicobacterpylori(H.pylori) reduced epithelial cell proliferation in H.pylori-infected gastric mucosa not showing intestinal metaplasia. The aim of this study was to dari~ the difference of the effect of H.py/ori eradication on cell turnover and p53 expression between intestinal metaplastic and non-metaplastic mucosa. Methods: Twenty-five patients in whom H.pylori had been eradicated (16 men, mean age; 56.8 years) with histologically confirmed chronic gastritis and 20 controls (13 men, mean age; 52.3 years) were enrolled in this study. Immunostaining of Ki67 and p53 (antibody; DAKO, Denmark) was performed using avidin-biotin method in biopsy specimens which were endoscopically taken from 5 points of the stomach recommended in the Updated Sydney System before and 1 year after H.pylorieradication. The rates of positive-stained cells (labeling index) were calculated followed by random selection of 3 epitheliums separatelyfrom intestinal metsplastic and non-metaplastic mucosa, and compared between before and after the therapy. Results were expressedas mean-+SDin Table. Conclusion: After H.pylorieradication, acceleration of epithelial cell turnover and over-expression of p53 were improved in non-intestinal metaplastic mucosa, but not in metaplastic one.
A-588
inflammation scores pre-treatment and no acute inflammation post-treatment. Conclusions Contrary to expectations, Helicobactergastritis did not significantly increase gastric antibiotic transfer. This may be due to the large inter-subject variability in gastric antibiotic secretion rates, which limits the usefulness of human experiments for examining gastric antibiotic secretion mechanisms.
Amoxycillin and Ampicillin Are Not Transtnred to Gastric Juice irrespective of Hollcobacfer pylori Status or Acid Blockade by Omeprazole Rodrigo M. Ortiz, Luiz R. Abreu, Silvana A. Callatatti, Andreia Cora77a,Maristela Deguer, Patricia Marques, Jos Pedrazzoli, USF, Braganca Pta Brazil
Gastricclearanceof antibiotics(mL/min) Ar~ibioUc
Amoxicillin
Clarithromycin
Melrontdazole
H, py/or/.ve volunteers H. py/or/+ve patients H. pylori -ve patients post.treatment
0.270 _+0.205 0.434 _+0,418
6.61 ± 2.82 5,66 ± 6 14
'1.85± 1.03 t.76 ± 0.76
0.362 + 0,361
10.10± 7 70
Background and aims: The effect of proton pum inhibitors and Hp infection on distribution of drugs employed for the eradication of this bacteria are poorly understood. The aim of this study was to investigate the effect of a 7-day administration of 20 mg omeprazole on the pharmacokinetics of amoxycillin and ampicillin in the palsma, saliva and gastric juice of individuals with and without Hp infection. Methods: 53 healthy volunteers without endoscopic lesions were enrolled. 24 volunteers were included in the amoxycillin study and 29 individuals in the ampicillin study. Each one has an open randomized two-period crossover design and a 21-day washout period between phases. Plasma, saliva and gastric juice concentrations of amoxycillin and ampicillin in subjects with and without omeprazole pre-treatment and with and without Hpinfection were measured by reversed-phaseHPLCwith ultraviolet detection.Results: Neither pre-treatment with pmeprazole nor Hp infection interfered with the plasma bioavailability as assessed by AUC~. Neither ampicillin were detected in saliva or gastric juice at any study phase. Conclusion: Short-term treatment with omperazole do not interfere with the pharmacokinetics of amoxycillin or ampicillin. Our results alsos exclude the presence of a transfer mechanism for amoxycillin or ampicillin from plasma to gastric juice.
2987 Clarithromycin MICs Level Against Helicobacter pylod (Hp) in Pro and Post Treatment Luigi Gatta, Dept of internal Medicine and Gastroenterology, Bologna Italy; Natale Figura, GI Unit, Siena Italy; Chiara Ricci, Dept of Internal Medicine and Gastroenterology, Bologna Italy; Luigi D'Anna, Military Hosp, Rome Italy; Marcello Menagatti, Federico Perna, Sonla Berardi, Andrea Tampieri, Dept of Internal Medicine and Gastroenterology, Bologna Italy; John Holton, Microbiology, UCL, London United Kingdom; Mario Miglioli, Dino Vaira, Dept of Internal Medicine and Gastroenterology, Bologna Italy
299O Cure of H./w/or/IntecUon Does Not Reduce COX-2 and Nitrntyrosine Expression in Gastric Mucoso with Intestinal Mntaplasia. Arats Kimura, Shiogo Tsuji, Masahiko Tsujii, Naoki Kawai, Masakazu Yasumaru, Yoshimi Kakiuchi, Yutska Sasaki, Masatsugu Hurt, Dept of Internal Medicine and Therapeutics, Soita City Japan; Sunao Kawano, Dept of C/in Lab Science, Sch of Allied
Aim: a) to evaluate the rate of susceptibility (S) to clarithromycin (C) in Hp strains isolated in our geographic area from patients nevertreated for Hp; b) to assessthe impact of resistance (R) and different levels of S to C on the treatment (ix) outcome; c) to determine secondary R rate and MICs value variations of C before and after 1~. Methods: over a 25 months period, 535 Hp strains were isolated from consecutive patients (M/F = 277/258; age range 18-86 yrs; mean age 50 yrs). S was assessed by E-test: C-R it MICgowas > 21g/ml. 457 (M/F=245/ 212; age range 18-84yrs; mean age 50 yrs) out of 535 HP patients were treated with PPI od + amoxicillin 1 g bd + C 500 mg bd for 7 days and 426 C MICs values were available. So far 174 (M/F = 105/69; age range 20-82yrs; mean age 50 yrs) out of 457 underwent endoscopy follow-up four weeks after stopping tx with re-evaluation of C-MICs if still Hp positive. Results: 92/426 (21%) were C-resistant and no significance differences were found according to gender (p>O,05). MICso75and ~ of C were 0,032, 0,094 and 64pg/ml respectively. The overall ratio of eradication in the 174 patients were 73% (n = 127). The one observed in 17 patients with C-resistant strains was 35,2% (6/17). The eradications in relation to the MICso ~ and ~ of C were 76%, 77% and 70% respectively. 34/47 cultures from not eradicated patients were obtained. The ratio of secondary resistant to C was 36% (9/25). We were also able to compare the pre and post b< MIC value for 18 strains. Post-tx MICs values of C for S strains that were still S after unsuccessful tx were the same only in 4 cases. In the other 6 S strains post-tx MICs were increased by 2-5 times. 6 strains became R to quite high levels. Conclusions: Our results suggest not to use C after unsuccessful treatment, even in cases in which strains are still susceptible.
Background and Aim: Accumulating body of evidence reveals that H. pylori(Hp) infection is a risk factor for gastric carcinogenesis, however, the mechanism for Helicobacter-related gastric carcinogenesis is unclear. Recent studies have demonstrated that cyciooxygenase 2 (COX-2) and nitric oxide (NO) have an important role for gastric carcinogenesis. However, the effects of Hp eradicafion on COX-2expression and NO production have not beenelucidated. The present study investigated the distribution of COX-2 and nitrotyrosine, a biologic marker for NO-related compounds in human gastric mucosa immunohistochemically and evaluated the expression before and after successful eradication of Hp infection in gastric mucosa with/ without intestinal metaplasia(IM), which is hypothesized to be a precancerous lesion of intestinal type of gastric cancer. Subjects and Methods: After informed consent was obtained, antral biopsy specimens were obtained from eight subjects(49.6 -+ 20.5 y)before and after eradication ofl-lp.lmmunohistochemical staining of COX-2/nitrotyrosine was performed and positive staining of COX-2/nitrotyrosine in the epithelium was expressed as the percentage of stained cells to the total epithelial cells The histoiogic status of the gastric mucosa was scored according to the updated Sydney system. Results: Graded variables except IM were significantly decreased after successful eradication of Hp (p
2988 Synergy Study of Rabeprazole in Combinationwith Mstrontdazole or Cladlkromycin Against Sensitive and Resistant Clinical H. pylor/Isolates. Andreas Mentis, Hellenic Pasteur Institute, Athens Greece; Theodore Rokkas, Henry Dunant Hosp, Athens Greece Rabeprazole (RAB), is a new proton pump inhibitor (PPI) and few in vitro data exist on its interaction with antibiotics commonly used for the treatment of H. pylori infection. Aim: To study the in vitro synergy of RAB and the antibiotics metronidazole (MET) or clarithromycin (CLA) against recently isolated clinical H. pylori strains exhibiting susceptibility or resistance to these antibiotics. Material and methods: The agar dilution chequerboard and the killing curve methods were employed. Twenty one H. pyloriclinical isolates and one reference strain were used in the chequerboard method. Eleven strains were susceptible to both antibiotics, whereas, ten were resistant to one or both antibiotics. The in vitro synergy was evaluated by the fractional inhibitory concentration (FIC) for each combination. Killing curves were constructed for RAB, MET and CLA individually and in combination at 0,5x, lx, and 2x MIC. The number of viable colonies was counted at 0,2,6,12, and 24h. Synergy with each combination was defined as a > 21og10reduction of CFU/mL compared with the most active agent alone. An agent was considered bactericidal if it produced a > 3 IoglO cfu/mL decrease from the initial inoculum. Results: In the chequerboard method, the minimum FIC ranged from 0,5 to 125 and the maximum FIC from 0,75 to 1,75. Synergy of the combination of MET and RAB as defined by an FICmin < 0.5 and partial synergy (FICmin between 0.5 and 1) was observed against one out of 10 strains exhibiting resistance to either MET / CLA or both antibiotics, and against 5 out of 11 sensitive H. pylori isolates. Synergy of the combination of CLA and RAB and partial synergy was observed against 3 out of 10 resistant, and against 6 out of 11 sensitive H. pylori isolates. In the time-kill assay, the combination of MET and RAB was synergistic against one, whereas the combination of CLA and RAB against three isolates. Synergistic effects were observed only when the strains were sensitive to both of the antibiotics investigated. Bactericidal effect was found against three isolates. No antagonism of any combination of RAB and the antibiotics was observed in any of the two methods. Conclusions. The combination of RAB with antibiotics was synergistic against a considerable number of /-/. py/ori strains. RAB plus CLA combination was synergistic (partially or totally) in a higher percentage of isolates compared to the RAB plus MET combination. This interaction was more profound against isolates sensitive to both antibiotics.
Effect of Helicobacler pylori Eradication on Epithelial Cell Turnover and p53 Expression of the Gastric Mucoso in Patients with Chronic Gastritis -Comparison Between Intestinal Mntaplastic and Non-Mntaplastic Mocosa Ryogo Sato, Toshio Fujioka, Kazunari Murakami, Masaaki Kodama, Tadayoshi Okimoto, Masaru Nasu, Oita Medical Univ, Oita Japan Background and aims: Some papers have indicated that epithelial cell turnover and p53 expression were acceleratedand eradication of Helicobacterpylori(H.pylori) reduced epithelial cell proliferation in H.pylori-infected gastric mucosa not showing intestinal metaplasia. The aim of this study was to dari~ the difference of the effect of H.py/ori eradication on cell turnover and p53 expression between intestinal metaplastic and non-metaplastic mucosa. Methods: Twenty-five patients in whom H.pylori had been eradicated (16 men, mean age; 56.8 years) with histologically confirmed chronic gastritis and 20 controls (13 men, mean age; 52.3 years) were enrolled in this study. Immunostaining of Ki67 and p53 (antibody; DAKO, Denmark) was performed using avidin-biotin method in biopsy specimens which were endoscopically taken from 5 points of the stomach recommended in the Updated Sydney System before and 1 year after H.pylorieradication. The rates of positive-stained cells (labeling index) were calculated followed by random selection of 3 epitheliums separatelyfrom intestinal metsplastic and non-metaplastic mucosa, and compared between before and after the therapy. Results were expressedas mean-+SDin Table. Conclusion: After H.pylorieradication, acceleration of epithelial cell turnover and over-expression of p53 were improved in non-intestinal metaplastic mucosa, but not in metaplastic one.
A-588