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Omeprazole plus triple therapy in the eradication of Helicobacter pylori
A106
AGA ABSTRACTS
O M E P R A Z O L E PLUS TRIPLE THERAPY IN THE E R A D I C A T I O N OF HELICOBACTER PYLORI Guti~rrez O.*,Melo M . * , S i e r r a F * * , R i c a u r t e O.*,Angel L.A* Otero W+ and Graham D.Y. *Unidad de G a s t r o e n t e r o l g i a y Patologia,Hospital San Juan de D i o s , U N i v e r s i d a d Nacional de C o l o m b i a , * * F u n d a c i 6 n Santa Fe,+Clinica Fundadores Bogota, ++ G a s t r o e n t e r o l o g y Division Baylor College of M e d i c i n e , H o u s t o n , T e x a s USA The treatment of H. pylori (Hp) is plenty of schedules but the ideal one is still unknown. The outcome of the different therapies depends on several factors such as bactericidal activity against H p , a n t i b i o t i c resistence, side effects and patient compliance. Triple therapy (TT) with Bismuth, M e t r o n i d a z o l e (MET) and t e t r a c y c l i n e (TET) has d e m o n s t r a t e d a high and consistent e r a d i c a t i o n effica cy. The AIM of this work is to evaluate if adding Omeprazole (OM)to TT improves the rate of Hp e r a d i c a t i o n PATIENTS AND METHODS. Patients with NUD and gastritis associated to H p h a v e been treated with OM 20 mg bid,Bis muth subsalicylate 2 tab qid, MET 250 mg qid and TET 500 mg qid for 14 days. Four weeks after the end of the end of the therapy an UGIE was done. Biopsies from the body and gastric antrum were taken for histology and fast urea se test for e v a l u a t i o n of Hp status RESULTS. 18 patients have been studied but only 14 accom plished the study ( 7 men ),.mean age 39.4~I0.I yrs. H.pylori eradication was observed in 12 out of 14 pts. (86%). 4/18 pts. (22%) were dropped out, 2 due to MET in tolerance and 2 due to a bad compliance. In the whole, 40 patients are expected to be studied CONCLUSIONS. This q u a d r u p l e therapy (OM+BSS+MET+TET) has an effective rate of H . p y l o r i eradication. However it seems that the results o b s e r v e d are no better than those obtained with a triple therapy or a c o m b i n a t i o n of a pro ton pump inhibitor. Pharmalogical interactions or in some of our patients a m e t r o n i d a z o l e r e s i s t e n c e could explain these results. With this schedule of treatment there also higher costs and an important number of withdraws.
O E X P R E S S I O N OF P - G L Y C O P R O T E I N S (P-GLY) IN T H E R O D E N T G A S T R I C M U C O S A : P O S S I B L E R O L E IN P H O S P H O L I P I D S E C R E T I O N . L.R. H a l l , E.J. Dial, G.S. S m i t h , a n d L.M. Lichtenberger. D e p a r t m e n t s o f Physiology and Cell Biology, and Surgery. University of Texas Medical School, Houston, Texas. The human M DR l gene encodes a P-gly which is a present i n the m e m b r a n e o f selected cells including tumor cells, and which can be induced to greater expression by exposure to anti-cancer drugs. P-gly acts as a p u m p to r e m o v e h y d r o p h o b i c a n t i - c a n c e r d r u g s w h i c h accumulate intracellularly, thereby imparting a multiple drug resistance (MDR) to these cells. In contrast, the MDR3 gene encodes a P-gly which has no effect on drug resistance, but m a y play a role in the secretion o f hydrophobic phospholipids from hepatocytes into bile (Cell 75:451462,1993). Our laboratory has obtained evidence that gastric epithelial cells have the capacity to secrete surface-active phospholipids, which m a y recruit to the luminal interface o f the m u c u s gel layer to f o r m a h y d r o p h o b i c b a r r i e r to l u m i n a l acid. Since the m e c h a n i s m o f phospholipid secretion has yet to be defined, we investigated whether Pgly was expressed in gastric mucosal tissue. Methods. Gastric mucosa and liver w e r e collected from mice and rats, and were analyzed by Western blotting using monoclonal antibody C219 (Signet Laboratories, Dedham MA) which reacts with P-gly from both MDR1 and 3. Frozen tissue s e c t i o n s o f g a s t r i c m u c o s a w e r e also e x a m i n e d b y immunocytochemistry. Results. Western blots of liver from both mice and rats showed a strong band of reactivity at 170kD, the molecular weight o f P-gly. in comparison, gastric mucosa from both mice and rats showed weaker, but consistent staining o f a 170kD band. Examination Of gastric mucosal tissue~sections revealed staining along the apical region o f surface mucous and parietal cells. No staining was seen in the lamina propria or muscle layers. Conclusions. P-gly is expressed in the gastric mucosa o f rodents where it is localized to cell surfaces that either secrete gastric acid or are exposed to it. This localization is consistent with a potential role for P-gly in the secretion of gastroprotective phospholipids, and m a y be a site for regulatory control. (Supported by N I H DK33239).
GASTROENTEROLOGY, Vol. 108, No. 4
THERE ARE DISCREPANCIES BETWEEN THE RESULTS OF ANTIMICROBIAL SUSCEPTIBILITY TESTING OF HEL/COBACTER PYLORI USING E-TEST COMPARED TO BROTH MICRODILUTION OR DISK DIFFUSION. C.Y. Hachem, J.E. Clarridge, R. Reddy, R. Flamm, D.G. Evans, D.Y. Graham. VAMC and Baylor College of Medicine, Houston, TX and Abbott Labs, Abbott Park, IL. The epsilometer agar diffusion gradient test (E-Test; AB Biodisk, Solna, Sweden) was compared to broth microdilution and paper disk diffusion for the antimicrobial susceptibility testing of H. pylori. A collection of 122 clinical isolates strains of Hp was tested for sensitivity to metronidazole, ampicillin and clarithromycin. All strains were tested on Mueller Hinton Agar supplemented with 5% sheep blood. Plates were incubated at 37 C in microaerophilic atmosphere and readings were done after 5 days of incubation according to manufacture's instruction. Strains were'considered resistant if the minimum inhibitory concentration(MIC) was >8 i.tg/mL for metronidazole or ampicillin and >2 I.tg/mL for clarithromycin. E-test MICs were easy to interpret. MICs determined by broth microdilution and E-test were highly reproducible with replicate results being within one 2-fold dilution. The correlation between MICs by the broth microdilution method and the E-test was good for clari and amp, with 96.7% and 98.2% respectively being within 1 and 2 two-fold dilution. However, for metronidazole only 80.3% were within 1 and 2 two-fold dilution and 12.3% of E-test results did not correlate to the broth method. Discrepancies occurred with E-test results between 4-16 gg/mL. In all cases the organism tested more resistant by the E-test making it appear that metronidazole resistance was more prevalent in a population than it might actually be. Disk diffusion results correlated with the broth microdilution in all cases. We conclude that when E-testing for MIC of metronidazole of H. pylori yields results in the 4-16 i.tg/mL range, the MIC should be reevaluated by another method.
HEL1COBACTER PYLORI ERADICATION SURVEILLANCE IN DENMARK TO PREVENT INAPPROPRIATE USE OF ANTIBIOTICS. PRELIMINARY RESULTS FROM A NATION-WIDE REGISTRATION OF ALL DRUG PRESCRIPTIONS. Hallas J, Nissen A, Thomson O0, Funch-Jensen P, Kolmos HI, Agerskov A, Iff,rag F.~ institute of Medical Biology, University of Odense; The National Board of Health; Dept. of Medical Gastroenterology, Healey Hospital, Depts. of Surgical Gastroenterology, Clinical Microbiology, and Medical Gastroenterology, Hvidovre Hospital, University of Copenhagen; The Danish Society of Gastroenterology,Denmark. Eradication of/L. pylori is now recommended in peptic ulcer disease. Previous experience with H2-blockers has revealed a consumption of five fold that justified by the number of ulcers. This pattern may apply to the/L, pylori eradication treatments as well. Om ~ were to monitor the total consumption in Denmark of H. pylori eradication treatments. Methods: All drug prescriptions in Denmark are recorded m a database allowing a demographic surveillance. H. pylori eradication treatment is identified by concomitant prescription of an anti-ulcer drug and appropriate antibiotics according to international recommendations. A preliminary surveillance was initiated 1991 in the county of Funen (465,239 inhabitants). Results (M=males, F=females): Age, years 20 - 34 35 - 49 50 - 64 65+ Total Sex M F M F M F M F M F t991 1992 1993
1 10 25
2 7 ll
1 4 16 18 37 32
5 8 44
4 15 38
5 17 27
10 15 43
12 51 133
20 55 124
Total 36 20 54 54 57 57 49 68 196 199 These 395 eradication treatments were given to 366 patients in 1991-1993; 21 patients = 5.7~ had two or more treatments. The estimated number of ulcer patients was 3,700. In 1993 the number of eradication treatments was eight times that of 1991. The slight predominance of women treated compared to the known M/F ratio of 2/1 in ulcer disease indicates that an ulcer probably has not been verified in all patients. In the same period 2,103 patients (2,814 preseiptions) received altemative combinations of ulcer drugs and antibiotics not usually recommended by gastroenterologists for H. pylori eradication. C.mlclusion: H. pylori eradication treatment has become increasingly frequent as replacement of traditional treatment. An inappropriate use of antibiotics seems in progress and a surveillance of the treatmenl policy is needed to prevent an unpredictable influence on the environment.
AGA ABSTRACTS
O M E P R A Z O L E PLUS TRIPLE THERAPY IN THE E R A D I C A T I O N OF HELICOBACTER PYLORI Guti~rrez O.*,Melo M . * , S i e r r a F * * , R i c a u r t e O.*,Angel L.A* Otero W+ and Graham D.Y. *Unidad de G a s t r o e n t e r o l g i a y Patologia,Hospital San Juan de D i o s , U N i v e r s i d a d Nacional de C o l o m b i a , * * F u n d a c i 6 n Santa Fe,+Clinica Fundadores Bogota, ++ G a s t r o e n t e r o l o g y Division Baylor College of M e d i c i n e , H o u s t o n , T e x a s USA The treatment of H. pylori (Hp) is plenty of schedules but the ideal one is still unknown. The outcome of the different therapies depends on several factors such as bactericidal activity against H p , a n t i b i o t i c resistence, side effects and patient compliance. Triple therapy (TT) with Bismuth, M e t r o n i d a z o l e (MET) and t e t r a c y c l i n e (TET) has d e m o n s t r a t e d a high and consistent e r a d i c a t i o n effica cy. The AIM of this work is to evaluate if adding Omeprazole (OM)to TT improves the rate of Hp e r a d i c a t i o n PATIENTS AND METHODS. Patients with NUD and gastritis associated to H p h a v e been treated with OM 20 mg bid,Bis muth subsalicylate 2 tab qid, MET 250 mg qid and TET 500 mg qid for 14 days. Four weeks after the end of the end of the therapy an UGIE was done. Biopsies from the body and gastric antrum were taken for histology and fast urea se test for e v a l u a t i o n of Hp status RESULTS. 18 patients have been studied but only 14 accom plished the study ( 7 men ),.mean age 39.4~I0.I yrs. H.pylori eradication was observed in 12 out of 14 pts. (86%). 4/18 pts. (22%) were dropped out, 2 due to MET in tolerance and 2 due to a bad compliance. In the whole, 40 patients are expected to be studied CONCLUSIONS. This q u a d r u p l e therapy (OM+BSS+MET+TET) has an effective rate of H . p y l o r i eradication. However it seems that the results o b s e r v e d are no better than those obtained with a triple therapy or a c o m b i n a t i o n of a pro ton pump inhibitor. Pharmalogical interactions or in some of our patients a m e t r o n i d a z o l e r e s i s t e n c e could explain these results. With this schedule of treatment there also higher costs and an important number of withdraws.
O E X P R E S S I O N OF P - G L Y C O P R O T E I N S (P-GLY) IN T H E R O D E N T G A S T R I C M U C O S A : P O S S I B L E R O L E IN P H O S P H O L I P I D S E C R E T I O N . L.R. H a l l , E.J. Dial, G.S. S m i t h , a n d L.M. Lichtenberger. D e p a r t m e n t s o f Physiology and Cell Biology, and Surgery. University of Texas Medical School, Houston, Texas. The human M DR l gene encodes a P-gly which is a present i n the m e m b r a n e o f selected cells including tumor cells, and which can be induced to greater expression by exposure to anti-cancer drugs. P-gly acts as a p u m p to r e m o v e h y d r o p h o b i c a n t i - c a n c e r d r u g s w h i c h accumulate intracellularly, thereby imparting a multiple drug resistance (MDR) to these cells. In contrast, the MDR3 gene encodes a P-gly which has no effect on drug resistance, but m a y play a role in the secretion o f hydrophobic phospholipids from hepatocytes into bile (Cell 75:451462,1993). Our laboratory has obtained evidence that gastric epithelial cells have the capacity to secrete surface-active phospholipids, which m a y recruit to the luminal interface o f the m u c u s gel layer to f o r m a h y d r o p h o b i c b a r r i e r to l u m i n a l acid. Since the m e c h a n i s m o f phospholipid secretion has yet to be defined, we investigated whether Pgly was expressed in gastric mucosal tissue. Methods. Gastric mucosa and liver w e r e collected from mice and rats, and were analyzed by Western blotting using monoclonal antibody C219 (Signet Laboratories, Dedham MA) which reacts with P-gly from both MDR1 and 3. Frozen tissue s e c t i o n s o f g a s t r i c m u c o s a w e r e also e x a m i n e d b y immunocytochemistry. Results. Western blots of liver from both mice and rats showed a strong band of reactivity at 170kD, the molecular weight o f P-gly. in comparison, gastric mucosa from both mice and rats showed weaker, but consistent staining o f a 170kD band. Examination Of gastric mucosal tissue~sections revealed staining along the apical region o f surface mucous and parietal cells. No staining was seen in the lamina propria or muscle layers. Conclusions. P-gly is expressed in the gastric mucosa o f rodents where it is localized to cell surfaces that either secrete gastric acid or are exposed to it. This localization is consistent with a potential role for P-gly in the secretion of gastroprotective phospholipids, and m a y be a site for regulatory control. (Supported by N I H DK33239).
GASTROENTEROLOGY, Vol. 108, No. 4
THERE ARE DISCREPANCIES BETWEEN THE RESULTS OF ANTIMICROBIAL SUSCEPTIBILITY TESTING OF HEL/COBACTER PYLORI USING E-TEST COMPARED TO BROTH MICRODILUTION OR DISK DIFFUSION. C.Y. Hachem, J.E. Clarridge, R. Reddy, R. Flamm, D.G. Evans, D.Y. Graham. VAMC and Baylor College of Medicine, Houston, TX and Abbott Labs, Abbott Park, IL. The epsilometer agar diffusion gradient test (E-Test; AB Biodisk, Solna, Sweden) was compared to broth microdilution and paper disk diffusion for the antimicrobial susceptibility testing of H. pylori. A collection of 122 clinical isolates strains of Hp was tested for sensitivity to metronidazole, ampicillin and clarithromycin. All strains were tested on Mueller Hinton Agar supplemented with 5% sheep blood. Plates were incubated at 37 C in microaerophilic atmosphere and readings were done after 5 days of incubation according to manufacture's instruction. Strains were'considered resistant if the minimum inhibitory concentration(MIC) was >8 i.tg/mL for metronidazole or ampicillin and >2 I.tg/mL for clarithromycin. E-test MICs were easy to interpret. MICs determined by broth microdilution and E-test were highly reproducible with replicate results being within one 2-fold dilution. The correlation between MICs by the broth microdilution method and the E-test was good for clari and amp, with 96.7% and 98.2% respectively being within 1 and 2 two-fold dilution. However, for metronidazole only 80.3% were within 1 and 2 two-fold dilution and 12.3% of E-test results did not correlate to the broth method. Discrepancies occurred with E-test results between 4-16 gg/mL. In all cases the organism tested more resistant by the E-test making it appear that metronidazole resistance was more prevalent in a population than it might actually be. Disk diffusion results correlated with the broth microdilution in all cases. We conclude that when E-testing for MIC of metronidazole of H. pylori yields results in the 4-16 i.tg/mL range, the MIC should be reevaluated by another method.
HEL1COBACTER PYLORI ERADICATION SURVEILLANCE IN DENMARK TO PREVENT INAPPROPRIATE USE OF ANTIBIOTICS. PRELIMINARY RESULTS FROM A NATION-WIDE REGISTRATION OF ALL DRUG PRESCRIPTIONS. Hallas J, Nissen A, Thomson O0, Funch-Jensen P, Kolmos HI, Agerskov A, Iff,rag F.~ institute of Medical Biology, University of Odense; The National Board of Health; Dept. of Medical Gastroenterology, Healey Hospital, Depts. of Surgical Gastroenterology, Clinical Microbiology, and Medical Gastroenterology, Hvidovre Hospital, University of Copenhagen; The Danish Society of Gastroenterology,Denmark. Eradication of/L. pylori is now recommended in peptic ulcer disease. Previous experience with H2-blockers has revealed a consumption of five fold that justified by the number of ulcers. This pattern may apply to the/L, pylori eradication treatments as well. Om ~ were to monitor the total consumption in Denmark of H. pylori eradication treatments. Methods: All drug prescriptions in Denmark are recorded m a database allowing a demographic surveillance. H. pylori eradication treatment is identified by concomitant prescription of an anti-ulcer drug and appropriate antibiotics according to international recommendations. A preliminary surveillance was initiated 1991 in the county of Funen (465,239 inhabitants). Results (M=males, F=females): Age, years 20 - 34 35 - 49 50 - 64 65+ Total Sex M F M F M F M F M F t991 1992 1993
1 10 25
2 7 ll
1 4 16 18 37 32
5 8 44
4 15 38
5 17 27
10 15 43
12 51 133
20 55 124
Total 36 20 54 54 57 57 49 68 196 199 These 395 eradication treatments were given to 366 patients in 1991-1993; 21 patients = 5.7~ had two or more treatments. The estimated number of ulcer patients was 3,700. In 1993 the number of eradication treatments was eight times that of 1991. The slight predominance of women treated compared to the known M/F ratio of 2/1 in ulcer disease indicates that an ulcer probably has not been verified in all patients. In the same period 2,103 patients (2,814 preseiptions) received altemative combinations of ulcer drugs and antibiotics not usually recommended by gastroenterologists for H. pylori eradication. C.mlclusion: H. pylori eradication treatment has become increasingly frequent as replacement of traditional treatment. An inappropriate use of antibiotics seems in progress and a surveillance of the treatmenl policy is needed to prevent an unpredictable influence on the environment.