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Metronidazole, omeprazole, and clarithromycin (MOC): An effective combination therapy for Helicobacter pylori infection
April 1995
• USE OF THE ["C]UREA BREATH TEST TO EVALUATE A NEW RAPID UREASE TEST FOR HELICOBACTER PI'LORI. Eneene L. young, and Alan F. Cutler. See. of Gastroenterology, Sinai Hospital, Detroit, Mi. Background: The CLO testTM, used to detect antral urease activity, requires refrigeration, lacks integral test controls and needs 24 hours for complete test results. PyloriTek TM may be stored at ruom temperature, contains integral controls and has a total test time of'two hours. 1'3C]urea breath test is frequently utilized to establish H. py/or/(Hp) infection. Aim: To compare the accuracy of PyloriTek TM and CLO test" in determining Hp infection status. Metbods: Patients, not previously treated tbr Hp, presenting for EGD were offered study inclusion. Two individual. antral biopsies were obtained from each patient during endoscopy, one for CLO testTM and the second for PyioriTek"t Each test method was numitored tbr colOr change at one and two hours. CLO testTM was also evaluated at 24 hours: Subjects underwent "C breath test after endoscopy to establish Hp infectkm status. When discordance occurred among the three test results, infection status was resolved by lgG serology utilizing ELISA (PyloriStat, Biowhittaker Inc). Results: 53 patients (25M/28F) with mean age 51.7+16.1 yrs. were entered in the study. 13/53 patients had a DU and/or GU. 28/53 patients were Hp positive. Three patients were positive by serology and both urease tests but were negative by breath test. One patient was deemed indeterminate, having only positive serology and PyloriTek TM but was treated as Hp negative for calculations. Sen. Stoic. PPV NPV CLO I,° 71% 100% 100% 76% 2* 79% 100% 100% 81% 24* 89% 100% 100% 89% PTek t ° 96% 92% 93% 96% 2* 100% 92% 93% 100% CLO 24°* 89% 100% 100% 89% PTek 2** 100% 96% 97% 100% * Indeterminate sample removed from analysis Conclusions: Both PyloriTekTM and CLO test" are specific and have go~k-I positive predictive value for determining H. py/or/infection. PyloriTekTM however has better sensitivity for H. pylori. Funded by Scrim Research.
• METRONIDAZOLE, OMEPRAZOLE, AND CLARITHROMYCIN (MOC): AN EFFECTIVE COMBINATION THERAPY FOR HELICOBACTERPYLORI INFECTION. M.M. Yousfi H.M.T. ElZimaity, M.T. A1-Assi, R.A. Cole, R.M. Genta, D.Y. Graham. Department of Medicine, V.A. Medical Center and Baylor College of Medicine, Houston, TX. Background: Cure ofH. pylori (Hp) infection cures peptic ulcer disease. Multi-drug regimens are generally required to reliably cure Hp infection. We studied the effectiveness and side effect profile of two antibiotics active against Hp, metronidazole and clarithromycin, combined with omeprazole. Methods: We evaluated the combination therapy for Hp infection consisting ofmetronidazole (500 mg b.i.d.), omeprazole (20 mg b.i.d), and clarithromycin (250 mg b.i.d.) for two weeks, followed by ranitidine 300 mg daily for four weeks. Results: Thirty-three patients with documented Hp infection were studied. Twenty had previously failed antimicrobial therapy, including 1 with metronidazole-based triple therapy and 8 with macrolide-based therapy (5 with clarithromycin-based therapy), and 11 with amoxicillin, tetracycline, and bismuth. Hp status was determined at entry and four weeks after completing antimicrobial therapy by histopathology using the Genta stain and by culture. The infection was cured in 88% (95% C.I. = 72% to 96%) including 90% of those who had failed previous anti-H, pylori therapies. Mild side effects were reported by 18o%. Antimicrobial sensitivity showed resistance to metronidazole in 21% and 9% to clarithromycin at entry. Four patients failed therapy: 1 patient's isolate was resistant to both and 1 patient's isolate was sensitive to both antimicrobialsboth before and after therapy, 1 was sensitive to both before therapy and developed resistance to metronidazole (compliance was 57%), and the last failure was resistant to clarithromycin before therapy and was resistant to both after therapy. Conclusions: The combination ofmetronidazole, omeprazole, and clarithromycin is an effective treatment for Hp infection even in patients with metronidazole resistant Hp, although development of metronidazole resistance may occur with treatment failure.
Esophageal, Gastric, and Duodenal Disorders
A265
UPPER GI BLEEDING IN POSTCORONARY STENT PATIENTS FOLLOWING ASPIRIN AND ANTICOAGULANT TREATMENT. Z,M~ Younossl, W.B. Strum, D. Cloutier, P.S. Telrstein, R.A. Schatz. Divisions of Gastroenterology and Cardiology, Scripps Clinic and Research Foundation, La Jolla, California.
Multiple studies link the use of nonsteroldal antiinflammatory drugs (NSAIDs) with severe upper gastrointestinal bleeding (UGIB) and the incidence is 2-4% (BMJ 300:278, 1990). Intracoronary stent placement to assure patency of the coronary arteries requires heparin and aspirin followed by a combination of aspirin and Coumadin®concurrently for 1 month. A 13-fold increase in the risk of developing UGIB with combination of oral anticoagulant and NSAIDs has been reported (Arch Intern Med 153:1665, 1993). We retrospectively assessed the incidence of UGIB in 138 coronary stent patients between 1990-1994 who were receiving heparin or Coumadln ® concurrently with aspirin, 325 mg/d. UGIB was defined as an episode of GI bleeding with a drop in hemoglobin associated with blood transfusion requirement, GI consultation or esophagogastroduodenoscopy (EGD). Patients were analyzed for multiple risk factors. UGIB occurred in 28 of 138 patients (20%; 95% confidence interval 13.3-26.7%) which is significantly higher than the rate of UGIB in those on NSAIDs alone. EGD findings on 28 patients with history of UGIB included 13 patients with esophagltis or gastritis, 7 patients with gastric or duodenal ulcers and 8 patients with no identifiable source. There was no mortality associated with UGIB. Ten patients required blood transfusion, with mean number of units - 5.3, SD - 2.7. Over 90% of these episodes of UGIB occurred within the first week of initiation of combination therapy. Previous history of NSAID use, peptic ulcer disease (PUB), smoking and prior or current use of antiulcer medication were not significantly different in cases which bled from those who did not bleed (p-value >0.i). Conclusion: The concurrent use of heparin or Coumadin ® with aspirin in coronary stent patients creates a significant potential for UGIB. The risk for bleeding cannot be predicted from prior history of NSAID use, PUD, smoking, antiulcer medications or current use of antiulcer medications.
• CHARACTERIZATION OF THE SOMATOSTATIN RECEPTOR SUBTYPE MEDIATING INHIBITION OF GASTRIN AND HISTAMINE SECRETION FROM THE ANTRUM OF HUMAN, DOG, AND RAT STOMACH. M. Zaki, L. Harrington, R. McCuen, D.H. Coy, G.M. Makhlouf, and M.L. Schubert. Medical College of Virginia and McGuire Veterans Affairs Medical Center, Richmond, VA. We have previously shown that somatostatin exerts a paracrine inhibitory influence on gastrin and histamine secretion in the gastric antrum. Recently, five different subtypes of somatostatin receptor, designated SSTR1-5, have been identified by molecular cloning techniques. The aim of the present study was to identify the somatostatin subtype regulating gastrin and histamine secretion. Antral mucosal segments from human, dog, and rat stomach were superfused with Krebs buffer in the presence of somatostatin-14 (SS-14) or various selective SSTR agonists. Release of gastrin and histamine was measured by radioimmunoassay. Addition of SS-14 or the SSTR2 selective agonist, EC 5-20, at 0.1 pM to 1 /zM caused a concentration-dependent decrease in basal gastrin and histamine secretion from human, dog, and rat antral segments (maximum decrease 40-60%; n=4-6). For all species, the threshold for gastrin and histamine secretion ranged from 0.1-10 pM. The ICaoconcentrations are given in the following Table: ICs0:
HUMAN SS-14 EC 5-20
Gastrin 100 pM Histamine 10 pM
10 pM 60 pM
DOG SS-14 EC 5-20
RAT SS-14 EC 5-20
30 pM 100 pM
40 pM 10 pM
10 pM 10 pM
10 pM 40 pM
The decrease in histamine secretion was not affected further by addition of the selective gastrin antagonists, L365260 or PD136450, implying that SS14 and EC 5-20 acted directly on the histamine cells. The SSTR3 agonist, DC25-12, and the SSTR4 agonist, DC 32-92, at concentrations up to 0.1 /~M had no significant effect on gastrin or histamine secretion in all three species. We eanelude that in human, dog, and rat antrum, somatostatin inhibits gastrin and histamine secretion by interacting with somatostatin SSTR2 receptors present on gastrin and histamine cells.
• USE OF THE ["C]UREA BREATH TEST TO EVALUATE A NEW RAPID UREASE TEST FOR HELICOBACTER PI'LORI. Eneene L. young, and Alan F. Cutler. See. of Gastroenterology, Sinai Hospital, Detroit, Mi. Background: The CLO testTM, used to detect antral urease activity, requires refrigeration, lacks integral test controls and needs 24 hours for complete test results. PyloriTek TM may be stored at ruom temperature, contains integral controls and has a total test time of'two hours. 1'3C]urea breath test is frequently utilized to establish H. py/or/(Hp) infection. Aim: To compare the accuracy of PyloriTek TM and CLO test" in determining Hp infection status. Metbods: Patients, not previously treated tbr Hp, presenting for EGD were offered study inclusion. Two individual. antral biopsies were obtained from each patient during endoscopy, one for CLO testTM and the second for PyioriTek"t Each test method was numitored tbr colOr change at one and two hours. CLO testTM was also evaluated at 24 hours: Subjects underwent "C breath test after endoscopy to establish Hp infectkm status. When discordance occurred among the three test results, infection status was resolved by lgG serology utilizing ELISA (PyloriStat, Biowhittaker Inc). Results: 53 patients (25M/28F) with mean age 51.7+16.1 yrs. were entered in the study. 13/53 patients had a DU and/or GU. 28/53 patients were Hp positive. Three patients were positive by serology and both urease tests but were negative by breath test. One patient was deemed indeterminate, having only positive serology and PyloriTek TM but was treated as Hp negative for calculations. Sen. Stoic. PPV NPV CLO I,° 71% 100% 100% 76% 2* 79% 100% 100% 81% 24* 89% 100% 100% 89% PTek t ° 96% 92% 93% 96% 2* 100% 92% 93% 100% CLO 24°* 89% 100% 100% 89% PTek 2** 100% 96% 97% 100% * Indeterminate sample removed from analysis Conclusions: Both PyloriTekTM and CLO test" are specific and have go~k-I positive predictive value for determining H. py/or/infection. PyloriTekTM however has better sensitivity for H. pylori. Funded by Scrim Research.
• METRONIDAZOLE, OMEPRAZOLE, AND CLARITHROMYCIN (MOC): AN EFFECTIVE COMBINATION THERAPY FOR HELICOBACTERPYLORI INFECTION. M.M. Yousfi H.M.T. ElZimaity, M.T. A1-Assi, R.A. Cole, R.M. Genta, D.Y. Graham. Department of Medicine, V.A. Medical Center and Baylor College of Medicine, Houston, TX. Background: Cure ofH. pylori (Hp) infection cures peptic ulcer disease. Multi-drug regimens are generally required to reliably cure Hp infection. We studied the effectiveness and side effect profile of two antibiotics active against Hp, metronidazole and clarithromycin, combined with omeprazole. Methods: We evaluated the combination therapy for Hp infection consisting ofmetronidazole (500 mg b.i.d.), omeprazole (20 mg b.i.d), and clarithromycin (250 mg b.i.d.) for two weeks, followed by ranitidine 300 mg daily for four weeks. Results: Thirty-three patients with documented Hp infection were studied. Twenty had previously failed antimicrobial therapy, including 1 with metronidazole-based triple therapy and 8 with macrolide-based therapy (5 with clarithromycin-based therapy), and 11 with amoxicillin, tetracycline, and bismuth. Hp status was determined at entry and four weeks after completing antimicrobial therapy by histopathology using the Genta stain and by culture. The infection was cured in 88% (95% C.I. = 72% to 96%) including 90% of those who had failed previous anti-H, pylori therapies. Mild side effects were reported by 18o%. Antimicrobial sensitivity showed resistance to metronidazole in 21% and 9% to clarithromycin at entry. Four patients failed therapy: 1 patient's isolate was resistant to both and 1 patient's isolate was sensitive to both antimicrobialsboth before and after therapy, 1 was sensitive to both before therapy and developed resistance to metronidazole (compliance was 57%), and the last failure was resistant to clarithromycin before therapy and was resistant to both after therapy. Conclusions: The combination ofmetronidazole, omeprazole, and clarithromycin is an effective treatment for Hp infection even in patients with metronidazole resistant Hp, although development of metronidazole resistance may occur with treatment failure.
Esophageal, Gastric, and Duodenal Disorders
A265
UPPER GI BLEEDING IN POSTCORONARY STENT PATIENTS FOLLOWING ASPIRIN AND ANTICOAGULANT TREATMENT. Z,M~ Younossl, W.B. Strum, D. Cloutier, P.S. Telrstein, R.A. Schatz. Divisions of Gastroenterology and Cardiology, Scripps Clinic and Research Foundation, La Jolla, California.
Multiple studies link the use of nonsteroldal antiinflammatory drugs (NSAIDs) with severe upper gastrointestinal bleeding (UGIB) and the incidence is 2-4% (BMJ 300:278, 1990). Intracoronary stent placement to assure patency of the coronary arteries requires heparin and aspirin followed by a combination of aspirin and Coumadin®concurrently for 1 month. A 13-fold increase in the risk of developing UGIB with combination of oral anticoagulant and NSAIDs has been reported (Arch Intern Med 153:1665, 1993). We retrospectively assessed the incidence of UGIB in 138 coronary stent patients between 1990-1994 who were receiving heparin or Coumadln ® concurrently with aspirin, 325 mg/d. UGIB was defined as an episode of GI bleeding with a drop in hemoglobin associated with blood transfusion requirement, GI consultation or esophagogastroduodenoscopy (EGD). Patients were analyzed for multiple risk factors. UGIB occurred in 28 of 138 patients (20%; 95% confidence interval 13.3-26.7%) which is significantly higher than the rate of UGIB in those on NSAIDs alone. EGD findings on 28 patients with history of UGIB included 13 patients with esophagltis or gastritis, 7 patients with gastric or duodenal ulcers and 8 patients with no identifiable source. There was no mortality associated with UGIB. Ten patients required blood transfusion, with mean number of units - 5.3, SD - 2.7. Over 90% of these episodes of UGIB occurred within the first week of initiation of combination therapy. Previous history of NSAID use, peptic ulcer disease (PUB), smoking and prior or current use of antiulcer medication were not significantly different in cases which bled from those who did not bleed (p-value >0.i). Conclusion: The concurrent use of heparin or Coumadin ® with aspirin in coronary stent patients creates a significant potential for UGIB. The risk for bleeding cannot be predicted from prior history of NSAID use, PUD, smoking, antiulcer medications or current use of antiulcer medications.
• CHARACTERIZATION OF THE SOMATOSTATIN RECEPTOR SUBTYPE MEDIATING INHIBITION OF GASTRIN AND HISTAMINE SECRETION FROM THE ANTRUM OF HUMAN, DOG, AND RAT STOMACH. M. Zaki, L. Harrington, R. McCuen, D.H. Coy, G.M. Makhlouf, and M.L. Schubert. Medical College of Virginia and McGuire Veterans Affairs Medical Center, Richmond, VA. We have previously shown that somatostatin exerts a paracrine inhibitory influence on gastrin and histamine secretion in the gastric antrum. Recently, five different subtypes of somatostatin receptor, designated SSTR1-5, have been identified by molecular cloning techniques. The aim of the present study was to identify the somatostatin subtype regulating gastrin and histamine secretion. Antral mucosal segments from human, dog, and rat stomach were superfused with Krebs buffer in the presence of somatostatin-14 (SS-14) or various selective SSTR agonists. Release of gastrin and histamine was measured by radioimmunoassay. Addition of SS-14 or the SSTR2 selective agonist, EC 5-20, at 0.1 pM to 1 /zM caused a concentration-dependent decrease in basal gastrin and histamine secretion from human, dog, and rat antral segments (maximum decrease 40-60%; n=4-6). For all species, the threshold for gastrin and histamine secretion ranged from 0.1-10 pM. The ICaoconcentrations are given in the following Table: ICs0:
HUMAN SS-14 EC 5-20
Gastrin 100 pM Histamine 10 pM
10 pM 60 pM
DOG SS-14 EC 5-20
RAT SS-14 EC 5-20
30 pM 100 pM
40 pM 10 pM
10 pM 10 pM
10 pM 40 pM
The decrease in histamine secretion was not affected further by addition of the selective gastrin antagonists, L365260 or PD136450, implying that SS14 and EC 5-20 acted directly on the histamine cells. The SSTR3 agonist, DC25-12, and the SSTR4 agonist, DC 32-92, at concentrations up to 0.1 /~M had no significant effect on gastrin or histamine secretion in all three species. We eanelude that in human, dog, and rat antrum, somatostatin inhibits gastrin and histamine secretion by interacting with somatostatin SSTR2 receptors present on gastrin and histamine cells.