Aliment. Pharmacol. Ther. (1992) 6, 503-506.
Short report: cefprozil for the eradication of Helicobacter pylori infection
H. MALATY," P. D. KLEIN,"tti5& D. Y. GRAHAM' 0.5 ,um01/min.~,~ Suppression of H. pylovi infection was defined as a negative I3C-urea breath test result while receiving active treatment. Eradication of the infection was defined as a negative I3C-ureabreath test 4-6 weeks post treatment. To identify suppression of the infection the I3C-urea breath test was repeated 2-3 days after initiation of treatment. The response to therapy was assessed by I3Curea breath test carried out within 2 days after completing the medicine and for those with negative tests it was repeated after 4 to 6 weeks. Treatment failure was defined as a positive urea breath test after therapy.
RESULTS Twelve subjects ranging in age from 26 to 56 years (mean 33 years) participated. There were seven Blacks and five Whites, six men and six women. As required, all 12 subjects were H.pylori-infected at entry. Suppression of the infection was
C E F P R O Z I L F O R H. PYLORI
505
documented 2-3 days after initiation of treatment in only 4 of 12 (33.3%).After therapy all 12 had a positive 13C-ureabreath test; the eradication rate was 0%. No serious averse events were reported. Two women subjects reported vaginal itching and discharge, and one subject reported a mild headache. DISCUSSION
H. pylori is now known to be the most common cause of gastritis and is closely associated with gastric ulcer, duodenal ulcer, and gastric carcinoma.' Eradication of
H. pylori infection results in healing of gastritis and a marked change in the natural history of peptic ulcer disease (that is, reduced or absent recurrence).lo-'*However, while H. pylovi is relatively easy to suppress, it is extraordinarily difficult to eradicate. Among the reasons for this discrepancy are diminished antimicrobial activity on exposure to the acid conditions of the stomach, rapid development of acquired resistance, patient non-compliance, and the fact that adherent organisms have different susceptibilities from those of unattached organisms, a biofilm phen~menon.~~," Triple-drug regimens have been relatively effective in eradicating H.pylori and eradication rates above 90 % have been achieved with combinations of a bismuth salt plus two antimicrobial agent^.'^''^ Monotherapies to eradicate H. pylovi have proven di~appointing.'~ The results of this study, showing eradication of H.pylori in none of the 12 subjects suggest that modifications in the treatment regimen will be required if it is to be useful (for example, can it replace metronidazole in triple therapy and thus be used to successfully eradicate H. pylori in those patients with metronidazole-resistant H.pylori for whom current therapies are often ineffective). ACKNOWLEDGEMENTS
This work was supported by the Department of Veterans Affairs, grant DK 39919 from the National Institute of Diabetes and Digestive and Kidney Diseases, by the US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, by a grant from Bristol-Myers Squibb, and by the generous support of Hilda Schwartz.
REFERENCES 1 Price A B. The Sydney system: histological division. J Gastroenterol Hepatol 1991; 6: 209-22. 2 Graham D Y. I. Helicobclcfer pylon: its epidemiology and its role in duodenal ulcer disease. J Gastroenterol Hepatol 1991; 6: 105-13.
3 Dixon M F. Helicobacbr pylori and peptic
ulceration : histological aspects. J Gastroenterol Hepatol 1991; 6: 125-30. 4 Rauws E A J, Langenberg W, Houthoff H J, Zanen H C, Tytgat G N J. Curnpylobacfer pyloridis-associated chronic active antral gastritis: a prospective study of its preva-
506
H.MALATY
ef a].
et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 1988; ii :
lence and the effects of antibacterial and antiulcer treatment. Gastroenterology 1988; 94: 33-40. 5 Coghlan J G, Gilligan D, Humphries H, et al. Campylobacter pylori and recurrence of duo-
6
7
8
9
denal ulcers-a 12-month follow-up study. Lancet 1987; ii: 1109-11. Graham D Y, Klein P D. What you should know about the methods, problems, interpretations, and uses of urea breath tests. Am J Gastroenterol 1991; 86: 1118-22. Graham D Y, Klein P D, Evans D G, et al. Simple noninvasive method to test efficacy of drugs in the eradication of Helicobacter pylori infection : the example of combined bismuth subsalicylate and nitrofurantoin. Am J Gastroenterol 1991; 86: 1158-62. Klein P D, Graham D Y. Campylobacfer pylori detection by the I3C-urea breath test. In: B Rathbone and V Heatley (eds.) Campylobacter pylori and Gastroduodenal Disease. Oxford : Blackwell Scientific Publications, 1989; 94-106. Graham D Y, Klein P D, Evans D J, Jr., et a2. Campylobacter pylori detected noninvasively by the I3C-urea breath test. Lancet 1987; i:
1437-42. 12 Rauws E A , Tytgat G N J. Cure of duodenal
ulcer associated with eradication of Helicobacter pylori. Lancet 1990; 335 : 1233-5. 13 George L L, Borody T J, Andrews P, et al. Cure of duodenal ulcer after eradication of Helicobacter pylori. Med J Aust 1990; 153: 145-9. 14 Graham D Y, Lew G M, Klein P D, et al.
15
16
17
1174-7. 10 Lambert
J R, Borromeo M, Korman M G, Hansky J, Eaves E R. Effect of colloidal bismuth (De-Nol) on healing and relapse of duodenal ulcers-role of Campylobacter pyloridis. Gastroenterology 1987; 92 : 1489. 11 Marshall B J, Goodwin C S, Warren J R,
18
Effect of treatment of Helicabacter pylori on the recurrence of gastric ulcers or duodenal ulcers: a randomized controlled study. Ann Intern Med 1992; 116: 705-8. Graham D Y, Borsch G M A. The who’s and when’s of therapy for Helicobacfer pyloui. Am J Gastroenterol 1990; 85: 1552-5. Megraud F, Trimoulet P, Lamouliatte H, Boyanova L. Bactericidal effect of amoxicillin on H . pylori in an in vitro model using epithelial cells. Antimicrob Agents Chemother 1991; 35 : 869-72. Borsch G M A, Graham D Y. Helicobacter pylori. In: Benjamin S B, Collen M J eds. Handbook of Experimental Pharmacology, Vol 99, Pharmacology of Peptic Ulcer Disease. Berlin : Spinger-Verlag, 1991; 107-48. Graham D Y, Lew G M, Malaty H M, et al. Factors influencing the eradication of Helicobacfer pylori with triple therapy. Gastroenterology 1992; 102: 493-6.
Short report: cefprozil for the eradication of Helicobacter pylori infection
H. MALATY," P. D. KLEIN,"tti5& D. Y. GRAHAM' 0.5 ,um01/min.~,~ Suppression of H. pylovi infection was defined as a negative I3C-urea breath test result while receiving active treatment. Eradication of the infection was defined as a negative I3C-ureabreath test 4-6 weeks post treatment. To identify suppression of the infection the I3C-urea breath test was repeated 2-3 days after initiation of treatment. The response to therapy was assessed by I3Curea breath test carried out within 2 days after completing the medicine and for those with negative tests it was repeated after 4 to 6 weeks. Treatment failure was defined as a positive urea breath test after therapy.
RESULTS Twelve subjects ranging in age from 26 to 56 years (mean 33 years) participated. There were seven Blacks and five Whites, six men and six women. As required, all 12 subjects were H.pylori-infected at entry. Suppression of the infection was
C E F P R O Z I L F O R H. PYLORI
505
documented 2-3 days after initiation of treatment in only 4 of 12 (33.3%).After therapy all 12 had a positive 13C-ureabreath test; the eradication rate was 0%. No serious averse events were reported. Two women subjects reported vaginal itching and discharge, and one subject reported a mild headache. DISCUSSION
H. pylori is now known to be the most common cause of gastritis and is closely associated with gastric ulcer, duodenal ulcer, and gastric carcinoma.' Eradication of
H. pylori infection results in healing of gastritis and a marked change in the natural history of peptic ulcer disease (that is, reduced or absent recurrence).lo-'*However, while H. pylovi is relatively easy to suppress, it is extraordinarily difficult to eradicate. Among the reasons for this discrepancy are diminished antimicrobial activity on exposure to the acid conditions of the stomach, rapid development of acquired resistance, patient non-compliance, and the fact that adherent organisms have different susceptibilities from those of unattached organisms, a biofilm phen~menon.~~," Triple-drug regimens have been relatively effective in eradicating H.pylori and eradication rates above 90 % have been achieved with combinations of a bismuth salt plus two antimicrobial agent^.'^''^ Monotherapies to eradicate H. pylovi have proven di~appointing.'~ The results of this study, showing eradication of H.pylori in none of the 12 subjects suggest that modifications in the treatment regimen will be required if it is to be useful (for example, can it replace metronidazole in triple therapy and thus be used to successfully eradicate H. pylori in those patients with metronidazole-resistant H.pylori for whom current therapies are often ineffective). ACKNOWLEDGEMENTS
This work was supported by the Department of Veterans Affairs, grant DK 39919 from the National Institute of Diabetes and Digestive and Kidney Diseases, by the US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, by a grant from Bristol-Myers Squibb, and by the generous support of Hilda Schwartz.
REFERENCES 1 Price A B. The Sydney system: histological division. J Gastroenterol Hepatol 1991; 6: 209-22. 2 Graham D Y. I. Helicobclcfer pylon: its epidemiology and its role in duodenal ulcer disease. J Gastroenterol Hepatol 1991; 6: 105-13.
3 Dixon M F. Helicobacbr pylori and peptic
ulceration : histological aspects. J Gastroenterol Hepatol 1991; 6: 125-30. 4 Rauws E A J, Langenberg W, Houthoff H J, Zanen H C, Tytgat G N J. Curnpylobacfer pyloridis-associated chronic active antral gastritis: a prospective study of its preva-
506
H.MALATY
ef a].
et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 1988; ii :
lence and the effects of antibacterial and antiulcer treatment. Gastroenterology 1988; 94: 33-40. 5 Coghlan J G, Gilligan D, Humphries H, et al. Campylobacter pylori and recurrence of duo-
6
7
8
9
denal ulcers-a 12-month follow-up study. Lancet 1987; ii: 1109-11. Graham D Y, Klein P D. What you should know about the methods, problems, interpretations, and uses of urea breath tests. Am J Gastroenterol 1991; 86: 1118-22. Graham D Y, Klein P D, Evans D G, et al. Simple noninvasive method to test efficacy of drugs in the eradication of Helicobacter pylori infection : the example of combined bismuth subsalicylate and nitrofurantoin. Am J Gastroenterol 1991; 86: 1158-62. Klein P D, Graham D Y. Campylobacfer pylori detection by the I3C-urea breath test. In: B Rathbone and V Heatley (eds.) Campylobacter pylori and Gastroduodenal Disease. Oxford : Blackwell Scientific Publications, 1989; 94-106. Graham D Y, Klein P D, Evans D J, Jr., et a2. Campylobacter pylori detected noninvasively by the I3C-urea breath test. Lancet 1987; i:
1437-42. 12 Rauws E A , Tytgat G N J. Cure of duodenal
ulcer associated with eradication of Helicobacter pylori. Lancet 1990; 335 : 1233-5. 13 George L L, Borody T J, Andrews P, et al. Cure of duodenal ulcer after eradication of Helicobacter pylori. Med J Aust 1990; 153: 145-9. 14 Graham D Y, Lew G M, Klein P D, et al.
15
16
17
1174-7. 10 Lambert
J R, Borromeo M, Korman M G, Hansky J, Eaves E R. Effect of colloidal bismuth (De-Nol) on healing and relapse of duodenal ulcers-role of Campylobacter pyloridis. Gastroenterology 1987; 92 : 1489. 11 Marshall B J, Goodwin C S, Warren J R,
18
Effect of treatment of Helicabacter pylori on the recurrence of gastric ulcers or duodenal ulcers: a randomized controlled study. Ann Intern Med 1992; 116: 705-8. Graham D Y, Borsch G M A. The who’s and when’s of therapy for Helicobacfer pyloui. Am J Gastroenterol 1990; 85: 1552-5. Megraud F, Trimoulet P, Lamouliatte H, Boyanova L. Bactericidal effect of amoxicillin on H . pylori in an in vitro model using epithelial cells. Antimicrob Agents Chemother 1991; 35 : 869-72. Borsch G M A, Graham D Y. Helicobacter pylori. In: Benjamin S B, Collen M J eds. Handbook of Experimental Pharmacology, Vol 99, Pharmacology of Peptic Ulcer Disease. Berlin : Spinger-Verlag, 1991; 107-48. Graham D Y, Lew G M, Malaty H M, et al. Factors influencing the eradication of Helicobacfer pylori with triple therapy. Gastroenterology 1992; 102: 493-6.
