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Only four days of quadruple therapy can effectively cure Helicobacter pylori infection
A80
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AGA ABSTRACTS
DUAL THERAPY OF OMEPRAZOLE PLUS AMOXICILLIN VERSUS QUADRUPLE THERAPY OF OMEPRAZOLE, BISMUTH, TETRACYCLINE AND METRONIDAZOLE FOR CURE OF H PYLORI INFECTION IN ULCER PATIENTS Results of a rendomised single center study. WA de Boer, WMM Driessen. Department of Internal Medicine, Sint Joseph Ziekenhuis, Veldhoven, the Netherlands. AIM. Eradication of H pylon from the stomach oures peptic ulcer disease. Ti'~refore eradication has become the goal of treatment in all ulcer patients. Many different treatment strategies have been proposed. The aim of this study was to compare dual therapy with quadruple therapy with regard to efficacy end side effect profile. METHODS. 76 consecutive patients with (chronic) ulcer disease but without active ulceration and biopsy proven H pylori infection referred to us between april end novsmber 1994 were included. They were randomised to omeprazole 20 mg bd day 1-10, colloidal bismuth subcitrate 120 mg qid day 4-10, tetracycline 500 mg qid day 4-10 end .metronidazole 500 mg lid day 4-10 (group I) or omeprazoie 20 mg bd day 1-14 and amoxicillin 1000 mg bd day 1-14 (group II). Cure was confirmed by a second endoscopy with 10 biopsies for urease test, histology end culture 6 weeks after treatment. A patient was considered outed if all 3 tests were negative. RESULTS. At december 1, 1994 50 patients had completed the entire protocol, 26 patients still need to be re-endoscoped. Interim analysis of these first 50 patients is as follows. 26/26 (100%, 95% CI 86.2% to 100%) patients in group I were cured. (16 carded a metronidazole sensitive strain, 4 carried a metronidazole resistent strain and in 6 it was not known.) Only 13/24 (54%, 95% CI 26.2% to 80.5%) were cored in group I1. The difference is highly significant (p<0,001) end further accrual for this study was stopped. Side effects were milder in group II but all patients in both groups could finish the complete course of treatment. CONCLUSION. Dual therapy is significantly less effective in curing H pylon infection as compared to quadruple therapy in peptic ulcer disease, Although side effects were somewhat milder with dual therapy, patients tolerated both treatments equally well. Dual therapy should not be used as a first line treatment strategy. We confirmed our previous findings that one week of quadruple therapy is well tolerated end that it is highly effective in metronidazole sensitive as well as in metronidazole resistent strains of H pylon with a cure rate approaching 100%. We therefore believe that this short qJJadrupie therapy is the best treatment for H pylon infection.
ONLY FOUR DAYS OF QUADRUPLE THERAPY CAN EFFECTIVELY CURE HEUCOBACTER PYLORI INFECTION. WA de Boer, WMM Ddessen. Sint Joseph Ziekanhuis, Veldhoven, the Nethedaods. AIM. Quadruple therapy (bismuth compound, tetracycline, metronidazole and omeprazole) dunng 7 days presently is the most optimal anti-Helicobacter treatment. It is highly effective (>95% cure) independent of metronidazole resistance end it has good patient tolerability. We investigated whether treatment duration can be reduced to 4 days. METHODS. 24 Patients with functional dyspepsia and biopsy proven N. pylori infection received omeprazole 20 mg bd day 1-7, Colloidal bismuth subcitrate 120 mg qid day 4-7, Tetracycline 500 mg qid day 4-7 end metreeidazole 500 mg day 4-7. Six weeks after therapy a second endoscopy was performed in all with 10 biopsies: 2(antrum) for CLOtest, 2(antrum) for culture end 6(2 antrum, 2 cardia, 2 corpus) for histology (Giemsa stain). A patient was considered cured if all 3 tests were negative. RESULTS. All patients finished the treatment. 20/24 patients (83.3%, 95% confidence interval 57.5%-99.3%) were cured from their H. pylori infection. In 4/24 patients CLOtsst, culture end histology were all positive. In 16/24 patients pre-treatment metronidazole resistance was known; 15 strains were metronidazole sensitive, 1 was resistant. The tour treatment failures occured in two patients with a sensitive strain (secondary metronidazele resistance was induced in these two patients), in the one patient with a resistant strain end in one patient in whom it was not known. CONCLUSIONS, We found 4 days of quadruple therapy after omeprazoie pretreatment to be effective end promising for cure of H pylori infection in dyspeptic patients. We are presently also testing this treatment in ulcer patients. For the time being the 7 day quadruple treatment remains the optimal therapy. However for patients on this therapy who suffer from severe side effects it seems possible to interrupt treatment after 4 days. Based on the result of this study it seems the chance for cure will probably not be substantially increased dudng the last 3 days of quadruple treatment.
GASTROENTEROLOGY, Vol. 108, No. 4
OMEPRAZOLE INCREASES THE EFFICACY OF TRIPLE THERAPY. RESULTS OF A RANDOMISED PROSPECTIVE STUDY OF TRIPLE THERAPY WITH OR WITHOUT OMEPRAZOLE FOR THE ERADICATION OF HEUCOBACTER PYLORI. WA de Boer, WMM Ddessen. Department of Internal Medicine, Sint Joseph Ziekenhuis, Veldhoven, the Nethedands. Successful eradication of H. pylon(HP) cures peptic ulcer disease. There is ongoing controversy as to the best treatment strategy for eradicating HP. We investigated whether omeprazole should be added to tdple therapy. METHODS. 108 Consecutive patients with (chronic) peptic ulcer disease, referred to us between june 1993 and apnl 1994, with biopsy proven HP infection but without active ulceration were randomised 1o either: omeprazale 20 mg bd day 1-10, colloidal bismuth subcitrate 120 mg qid day 4-10, tetracycline 500 mg qid day 4-10 and metronidazole 500 mg tid day 4-10 (group I, n=54). Or the same triple therapy without omeprazole from day 1-7 (group II, n=54). 4-6 Weeks after the end of treatment a second endoscopy was performed with 10 biopsies; 2 (antrum) for CLO-test, 2 (antrum) for culture end 6 (2 antrum, 2 corpus, 2 cardia) for histology (Giemsa stain). A patient was considered cured if all 3 tests were negative for NP. RESULTS. Follow-up was achieved in all 108 patients, 2 refused endoscopy, b~t had a 14C-breath test (1 positive, 1 negative). Altogether 53/54 (98.1%) patients in group I (95% CI: 89%-100%) were eradicated versus 45/54 (83.3%) patients in group II (95%C1: 67%-95%) (p=0,008) Pre-treatment sensitivity testing was performed in 65 patients. 60 were metronidazole sensitive, of these 27/28 (96.4%) were eradicated in group I versus 29/32 (90.6%) in group II (NS). In group I 3/3 (100%) with a metronidazole resistent strain were eradicated versus 0/2 (0%) in group II (p=0,025) Side effects were mild end did not interfere with compliance. 105/108 (97.2%) patients finished the complete treatment. Gastro-intestinal side-effects occured significantly less in group I. 1 Patient developed pseudomembrenous colitis. CONCLUSION. One week o1 quadruple therapy is superior to one week of triple therapy. Presently it is the best treatment for HP associated peptic ulcers. It combines excellent efficacy (>95%) independent of rnetronidazole resistance, good relief of ulcer pain end good tolerability. Omeprazole pre-treatment does not interfere with the efficacy of this treatment.
T H E EFFECT ON I N T R A G A S T R I C pH OF OPIOID ANESTHESIA VERSUS • PERIDURAL A N A L G E S I A IN M A J O R SURGERY. J.A.M. de Haas I, W.P. Geus 1~, and C.B.H.W.l.amers 2.
1Dept. of lntensive Care, Leyenburg Hospital, The Hague, and 2Dept. of Gastroenterology, University Hospital Le~den, the Netherlands. Opioids used in anesax~ia may enhanue inlragaslricpH due to inhibition of gaslroimcs~ motility.Aim of tim studywas to gain insightinthe effectof opioidsused during anesthesiaon intragastr~pH palton~ in palientsduring and a.~r abdominal aortic reconstructivesurgery.The effect on intraga~ic pH of opioid (sufcnmml followed by nitrous oxide, group I) was compared with the effect on inOagastric pH of peridural analgesia Coupivacain 0.5% followed by a continuous infusion of propofol, group I~ during a 72-hr intra- and postoperative period. Inwagastfic pH was monitored continuously in 20 paticats (10 in eanh group) with glass eleetrodes~ in~rtcd transnasallyand positionedin the gastriccolpus at the beginningof surgery. Prior to the induction of auesthesia, no prophylaeuc antacids or antJsecretory agents were used. Results: Both study groups were comparable with respect to age and daily APACHE 11 score. On day I median 24-h pH in group I1 was 2.35 and 6.75 in group 1, respecavely (p < 0.05). Median 24-h pH on day 2 was 1.7 in group I1, and 3.2 in group I (p < 0.05). On day 3 median 24-h pH was 1.5 in groap 11 and 1.65 in group I (n.s.). In group II a significant lowering of mlragastfic pH was observed from the first 8-hr period to the 8- to 16-hr interval (4.25 to 2.35, 8--hr medians). In group I a significant loxsering of inlragastnc pH was found after the 24- to 32-hr interval (6.75 to 2.6). In group II no furtber significant decrease of in~agastxic pH was observed from tbe 32- to 40-b,r interval (1.65) until the final 8-hr study period (1.6). No further significant decrease of inlragastfic pH was fouod in group I from the 40- to 48-hr interval (2.1) until the last 8hr period (1.7). Median 8-h pH values of group II were significant lower than the corresponding median pH values of group I from the first to the fiRh 8-hr interval. Interpatient and inWapatient variation in median 8-hr pH values in group 1I were less than in group 1.
Conclusions: This study, dem~-tmtes during the first 32- to 40-hr a f a r the beginning of surgery: l) a high intragastric pH in patients who received opioid anesthesia. 2) a significant lower intragastric pH and a faster restoration of intragastric pH pay.eros in patients who received anesthesia without opioids may be due to a lesser disturbanue of gastrointestinal motility.
•
AGA ABSTRACTS
DUAL THERAPY OF OMEPRAZOLE PLUS AMOXICILLIN VERSUS QUADRUPLE THERAPY OF OMEPRAZOLE, BISMUTH, TETRACYCLINE AND METRONIDAZOLE FOR CURE OF H PYLORI INFECTION IN ULCER PATIENTS Results of a rendomised single center study. WA de Boer, WMM Driessen. Department of Internal Medicine, Sint Joseph Ziekenhuis, Veldhoven, the Netherlands. AIM. Eradication of H pylon from the stomach oures peptic ulcer disease. Ti'~refore eradication has become the goal of treatment in all ulcer patients. Many different treatment strategies have been proposed. The aim of this study was to compare dual therapy with quadruple therapy with regard to efficacy end side effect profile. METHODS. 76 consecutive patients with (chronic) ulcer disease but without active ulceration and biopsy proven H pylori infection referred to us between april end novsmber 1994 were included. They were randomised to omeprazole 20 mg bd day 1-10, colloidal bismuth subcitrate 120 mg qid day 4-10, tetracycline 500 mg qid day 4-10 end .metronidazole 500 mg lid day 4-10 (group I) or omeprazoie 20 mg bd day 1-14 and amoxicillin 1000 mg bd day 1-14 (group II). Cure was confirmed by a second endoscopy with 10 biopsies for urease test, histology end culture 6 weeks after treatment. A patient was considered outed if all 3 tests were negative. RESULTS. At december 1, 1994 50 patients had completed the entire protocol, 26 patients still need to be re-endoscoped. Interim analysis of these first 50 patients is as follows. 26/26 (100%, 95% CI 86.2% to 100%) patients in group I were cured. (16 carded a metronidazole sensitive strain, 4 carried a metronidazole resistent strain and in 6 it was not known.) Only 13/24 (54%, 95% CI 26.2% to 80.5%) were cored in group I1. The difference is highly significant (p<0,001) end further accrual for this study was stopped. Side effects were milder in group II but all patients in both groups could finish the complete course of treatment. CONCLUSION. Dual therapy is significantly less effective in curing H pylon infection as compared to quadruple therapy in peptic ulcer disease, Although side effects were somewhat milder with dual therapy, patients tolerated both treatments equally well. Dual therapy should not be used as a first line treatment strategy. We confirmed our previous findings that one week of quadruple therapy is well tolerated end that it is highly effective in metronidazole sensitive as well as in metronidazole resistent strains of H pylon with a cure rate approaching 100%. We therefore believe that this short qJJadrupie therapy is the best treatment for H pylon infection.
ONLY FOUR DAYS OF QUADRUPLE THERAPY CAN EFFECTIVELY CURE HEUCOBACTER PYLORI INFECTION. WA de Boer, WMM Ddessen. Sint Joseph Ziekanhuis, Veldhoven, the Nethedaods. AIM. Quadruple therapy (bismuth compound, tetracycline, metronidazole and omeprazole) dunng 7 days presently is the most optimal anti-Helicobacter treatment. It is highly effective (>95% cure) independent of metronidazole resistance end it has good patient tolerability. We investigated whether treatment duration can be reduced to 4 days. METHODS. 24 Patients with functional dyspepsia and biopsy proven N. pylori infection received omeprazole 20 mg bd day 1-7, Colloidal bismuth subcitrate 120 mg qid day 4-7, Tetracycline 500 mg qid day 4-7 end metreeidazole 500 mg day 4-7. Six weeks after therapy a second endoscopy was performed in all with 10 biopsies: 2(antrum) for CLOtest, 2(antrum) for culture end 6(2 antrum, 2 cardia, 2 corpus) for histology (Giemsa stain). A patient was considered cured if all 3 tests were negative. RESULTS. All patients finished the treatment. 20/24 patients (83.3%, 95% confidence interval 57.5%-99.3%) were cured from their H. pylori infection. In 4/24 patients CLOtsst, culture end histology were all positive. In 16/24 patients pre-treatment metronidazole resistance was known; 15 strains were metronidazole sensitive, 1 was resistant. The tour treatment failures occured in two patients with a sensitive strain (secondary metronidazele resistance was induced in these two patients), in the one patient with a resistant strain end in one patient in whom it was not known. CONCLUSIONS, We found 4 days of quadruple therapy after omeprazoie pretreatment to be effective end promising for cure of H pylori infection in dyspeptic patients. We are presently also testing this treatment in ulcer patients. For the time being the 7 day quadruple treatment remains the optimal therapy. However for patients on this therapy who suffer from severe side effects it seems possible to interrupt treatment after 4 days. Based on the result of this study it seems the chance for cure will probably not be substantially increased dudng the last 3 days of quadruple treatment.
GASTROENTEROLOGY, Vol. 108, No. 4
OMEPRAZOLE INCREASES THE EFFICACY OF TRIPLE THERAPY. RESULTS OF A RANDOMISED PROSPECTIVE STUDY OF TRIPLE THERAPY WITH OR WITHOUT OMEPRAZOLE FOR THE ERADICATION OF HEUCOBACTER PYLORI. WA de Boer, WMM Ddessen. Department of Internal Medicine, Sint Joseph Ziekenhuis, Veldhoven, the Nethedands. Successful eradication of H. pylon(HP) cures peptic ulcer disease. There is ongoing controversy as to the best treatment strategy for eradicating HP. We investigated whether omeprazole should be added to tdple therapy. METHODS. 108 Consecutive patients with (chronic) peptic ulcer disease, referred to us between june 1993 and apnl 1994, with biopsy proven HP infection but without active ulceration were randomised 1o either: omeprazale 20 mg bd day 1-10, colloidal bismuth subcitrate 120 mg qid day 4-10, tetracycline 500 mg qid day 4-10 and metronidazole 500 mg tid day 4-10 (group I, n=54). Or the same triple therapy without omeprazole from day 1-7 (group II, n=54). 4-6 Weeks after the end of treatment a second endoscopy was performed with 10 biopsies; 2 (antrum) for CLO-test, 2 (antrum) for culture end 6 (2 antrum, 2 corpus, 2 cardia) for histology (Giemsa stain). A patient was considered cured if all 3 tests were negative for NP. RESULTS. Follow-up was achieved in all 108 patients, 2 refused endoscopy, b~t had a 14C-breath test (1 positive, 1 negative). Altogether 53/54 (98.1%) patients in group I (95% CI: 89%-100%) were eradicated versus 45/54 (83.3%) patients in group II (95%C1: 67%-95%) (p=0,008) Pre-treatment sensitivity testing was performed in 65 patients. 60 were metronidazole sensitive, of these 27/28 (96.4%) were eradicated in group I versus 29/32 (90.6%) in group II (NS). In group I 3/3 (100%) with a metronidazole resistent strain were eradicated versus 0/2 (0%) in group II (p=0,025) Side effects were mild end did not interfere with compliance. 105/108 (97.2%) patients finished the complete treatment. Gastro-intestinal side-effects occured significantly less in group I. 1 Patient developed pseudomembrenous colitis. CONCLUSION. One week o1 quadruple therapy is superior to one week of triple therapy. Presently it is the best treatment for HP associated peptic ulcers. It combines excellent efficacy (>95%) independent of rnetronidazole resistance, good relief of ulcer pain end good tolerability. Omeprazole pre-treatment does not interfere with the efficacy of this treatment.
T H E EFFECT ON I N T R A G A S T R I C pH OF OPIOID ANESTHESIA VERSUS • PERIDURAL A N A L G E S I A IN M A J O R SURGERY. J.A.M. de Haas I, W.P. Geus 1~, and C.B.H.W.l.amers 2.
1Dept. of lntensive Care, Leyenburg Hospital, The Hague, and 2Dept. of Gastroenterology, University Hospital Le~den, the Netherlands. Opioids used in anesax~ia may enhanue inlragaslricpH due to inhibition of gaslroimcs~ motility.Aim of tim studywas to gain insightinthe effectof opioidsused during anesthesiaon intragastr~pH palton~ in palientsduring and a.~r abdominal aortic reconstructivesurgery.The effect on intraga~ic pH of opioid (sufcnmml followed by nitrous oxide, group I) was compared with the effect on inOagastric pH of peridural analgesia Coupivacain 0.5% followed by a continuous infusion of propofol, group I~ during a 72-hr intra- and postoperative period. Inwagastfic pH was monitored continuously in 20 paticats (10 in eanh group) with glass eleetrodes~ in~rtcd transnasallyand positionedin the gastriccolpus at the beginningof surgery. Prior to the induction of auesthesia, no prophylaeuc antacids or antJsecretory agents were used. Results: Both study groups were comparable with respect to age and daily APACHE 11 score. On day I median 24-h pH in group I1 was 2.35 and 6.75 in group 1, respecavely (p < 0.05). Median 24-h pH on day 2 was 1.7 in group I1, and 3.2 in group I (p < 0.05). On day 3 median 24-h pH was 1.5 in groap 11 and 1.65 in group I (n.s.). In group II a significant lowering of mlragastfic pH was observed from the first 8-hr period to the 8- to 16-hr interval (4.25 to 2.35, 8--hr medians). In group I a significant loxsering of inlragastnc pH was found after the 24- to 32-hr interval (6.75 to 2.6). In group II no furtber significant decrease of in~agastxic pH was observed from tbe 32- to 40-b,r interval (1.65) until the final 8-hr study period (1.6). No further significant decrease of inlragastfic pH was fouod in group I from the 40- to 48-hr interval (2.1) until the last 8hr period (1.7). Median 8-h pH values of group II were significant lower than the corresponding median pH values of group I from the first to the fiRh 8-hr interval. Interpatient and inWapatient variation in median 8-hr pH values in group 1I were less than in group 1.
Conclusions: This study, dem~-tmtes during the first 32- to 40-hr a f a r the beginning of surgery: l) a high intragastric pH in patients who received opioid anesthesia. 2) a significant lower intragastric pH and a faster restoration of intragastric pH pay.eros in patients who received anesthesia without opioids may be due to a lesser disturbanue of gastrointestinal motility.