January 09.pmd

EDITORIAL
Treatment Strategies for Helicobacter pylori Eradication: Current
Perspective
All over the world anti-microbial based triple practice. Resistance to metroindazole and clarithromycin therapy is the standard treatment but eradication rates is much more important clinically and resistance to one have declined to the extent that alternative or salvage of these agents leads to failed therapy. Resistance to therapies using levofloxicin and rifabutin have gained clarithromycin is caused by mutation in the organism that importance. Seqential therapy is a newly described prevents binding to the antibiotic to the ribosome of H.
regimen that has been in many studies shows to be pylori thereby preventing interruption of action of H. pylori infection has been falling in developed Metronidazole is a prodrug that must be reduced countries. Challenges with eradication have increased in the cell to have an adverse effect on bacterial. DNA as the resistant strains of H. pylori have increased. The Mutation in gene called rdx A has been associated with eradication rates have decreased to 65% with confidence metronidazole resistance.6 Metronidazole resistance interval (CIS) ranging from 57-73%.1 Clarythromycin causes an efficacy reduction of 50% with triple and resistance is 13% in America, metronidazole resistance is common in Asia.1,2 A study from Kuwait reported Recent recommen-dations of European H. pylori high resistance to metronidazole but no resistance to study group and American College of Gastroenterologist clarithromycin.3 In Iran, resistance to clarithromycin is recommend triple therapy(proton pump inhhibitor+ amoxicillin+clarithromycin) as initial therapy for treatment Anti-microbial therapy used for eradication of H. of H. pylori.17,18 Quadruple therapy (proton pump pylori was developed for the treatment of other infections inhibitor+bismuth+metronidazole+tetracycline) is an and was not specificaly developed to achieve high alternative initial therapy. In an Irish study triple therapy concentration in gastric mucosa where H. pylori reside.
was successful in 77% + Bismuth based quadriple Proton pump inhibition have been used to improve drug therapy or alternative therapy was successful on 56%.7 concentraton in gastric juice along with anti-microbial In another study in Greece patients initially treated with agents to improve eradication of H. pylori infection.
PPI triple therapy failure were given quadruple therapy Non-complaince of anti-microbial agents is a and patients failing treatment were given levofloxcin triple major clinical problem. It is difficult to adhere to quadruple therapy and achieved eradication rate of 89.6%.29 A therapies which require ingestion of drugs four times daily.
study from Spain reported a success rate of 99.5% when Intolerable side effects associated with prolonged courses traditional therapy was used and salvage therapies were of treatment can lead to non-compliance. Sequential adminsitered to those who fail triple therapy.
therapy and compliance packs can help with adherence to drug regimen. Addition of proton pump inhibitors to tetracycline+proton pump inhibitors) adminstered for 7- anti-microbial therapy decreases the viscosity of gastric 10 days is particularly useful tratment where metro- mucosa and increases its permeability. Clarithromycin is nidazole resistance is low and clarithromycin resistance very sensitive to degradation by gastric acid and has half is high. In a large randomized controlled trial, eradication life of less than 1 hour at pH of 2.5Metronidazole is stable rates were similar in proton pump triple therapy (78%) in gastric juice regardless of pH with half life of 800 hours.
and quadriple therapy 82%. A major disadvantage is Amoxicillin is less stable in low pH with half life of 15 that 3 tablets are needed to be taken 4 times daily. In addition a proton pump inhibitor must be taken twice Amoxicillin and metroindazole or tinidazole form daily. This regimen is associated with poor adherence.
the corner stone of treatment regimen. Combination of In one study performed between 1997 and 1999 drugs that do not contain any of these agents have poor patients received a 5 day treatment with 3 antibiotics, efficacy. Resistance to amoxicillin is very rare in clinical amoxicillin 1 gm twice daily, clarithromycin in 250mg Journal of Medical Sciences Vol. 12 No.1 (Jan. 2009) twice daily, metrogyle 400mg twice daily alongwith PPI.
pylori by 7-day triple-therapy regimens combining Recommendations for this therapy have surfaced recently pantoprazole with clarithro-mycin, metronidazole, or with new name "concurrent or concomittant therapy".
amoxicillin in patients with peptic ulcer disease:results Sequential therapy is a novel treatment method.
of two double-blind, randomized studies. Helicobacter. Instead of administering the anti-microbial all at once, they are administered in sequence; this reduces side Duck WM, Sobel J, Pruckler JM, Song Q, Swerdlow D, effects. This treatment strategy was developed based et al. Antimicrobial resistance incidence and risk factors upon the observation that dual drug therapy were still in among Helicobacter pylori-infected persons. United use. Studies conducted have demonstrated that States Emerg Infect Dis. 2004;10:1088-94.
eradication rate achieved with a therapeutic strategy of John Albert M, Al-Mekhaizeem K, Neil L, Dhar R, intially administering 14 day dual therapy in individuals Dhar PM, et al. High prevalence and level of resistance who failed. The regional therapy was better than reverse to metronidazole, but lack of resistance to other sequence (7-day triple therapy as initial strategy with 14 antimicrobials in Helicobacter pylori, isolated frommultiracial population in Kuwait. Aliment Pharmacol days dual therapy for failures).9 The sequential therapy is best described as 10 day treatment consisting of PPI Mohammadi M, Doroud D, Mohajerani N, Massarat S.
and amoxicillin 1 gm (both twice daily) administered for Helicobacter pylori antibiotic resistance in Iran. World first 5 days followed by triple therapy (PPI+ clari- thromycin 500 mg BD, tinidazole 500 mg BD) for Goddard A. Review article: factors inluencing antibiotic remaining 5 days. A recent meta analysis of 10 trials transfer across the gastric mucosa. Aliment Pharmacol Levofloxacin and rifabutin are treatment for Goodwin A, Kersulyre D, Sisson G, Veldhuyzen van patients in whom standard treatment fails. Ten days Zanten SJ, Berg DE, Hoffman PS. Metronidazole resis- levofloxacin triple therapy was superior to 7 days therapy tance in Helicobacter pylori is due to null mutations in and lower dose of levofloxicin (250 mg twice daily) was a gene (rdxA)that encodes an oxygen-insensitive effective as high dose (500 mg twice daily). In a NADPH intro-reductase. Mol Microbiol. 1998;28:383- randomized comparison of levofloxicin therapy and rifabutin triple therapy in patients with failed otehr Sharma VK, Howden CW. A national survey of primary treatment, levofloxicin triple therapy was superior to care physicians' perceptions and practices related to Helicobacter pylori infection. J Clin Gastrointerol. In conclusion there are two main therapeutic strategies: tradition and emergent. Tradition therapy is Gisbert JP, Gisbert JL, Marcos S, Jimenez-alonso I, based upon sound evidence. These treatment regimens Moreno-Orero R, Pajares JM. Empirical rescue therapy are effective but substantial number of patients require a after Helicobacter pylori treatment failure: a single centre second course of treatment. Sequential therapy has study of 500 patients. Aliment Pharmacol Ther. emerged new mode of treatment which has high degree of success in many trials around the world and makes it Rinaldi V, Zullo A, Pugliano F, Valente C, Diana F, Attli AF. The management of failed dual or triple therapy forHelicobacter pylori eradication. Aliment Pharmacol Gatta L, Di Mario F, Zullo A, Vaira D. Errors in a metaanalysis of treatments for Helicobacter pylori infection. Ann Ingtern Med. 2008;149:686.
Van der Poorten D, Katelaris PH. The effectivenessof rifabutin triple therapy for patients with difficult-to-eradicate Helicoabcter pylori in clinical practice.
REFERENCES
Aliment Pharmacol Ther. 2007;26:1537-42.
Bochenek WJ, Peters S, Praga PD, Wang W, Mack ME, Nimish Vakil. Helocobacter pylori eradication.
et al. Helobacter pylori Pantoprazole Eradication Sequential and tetracycline therapy. Gastroenterology (HELPPE) Study Group. Eradication of Helicobacter Journal of Medical Sciences Vol. 12 No.1 (Jan. 2009)

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