H. pylori (HP) eradication with omeprazole (O), metronidazole (M) and amoxycillin (a): The impact of drug dosing &amp; resistance on efficacy — The homer story

Bardhan, K. D.; Bayerdörffer, Ekkehard; Delchier, J-P; Hellblom, M; Mégraud, F; Stubberöd, A; Zenten, Sjo Veldhuyzen van; Lind, Tore; Burman, C. E. L.; Gromark, P-O

doi:10.1016/s0016-5085(98)80264-3

Cited by 10 publications

(7 citation statements)

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“…As pre‐treatment metronidazole resistance has generally been shown to be an adverse determinant of outcome when using metronidazole‐containing triple therapies, the results of this study are very relevant to clinical practice. Whereas an overall eradication rate of around 80% was achievable with omeprazole, amoxycillin and metronidazole (OAM) in the HOMER and HERA Studies 9 , 10 this is not reproduced in the present study. The results are about 20% inferior to this with the difference largely accounted for by the increased proportion of pre‐treatment metronidazole resistant patients (20% vs. 56%).…”

Section: Discussionsupporting

confidence: 88%

“…The reported prevalence of pre‐treatment metronidazole resistance in those trials has usually been 18–30% 1 , . 7 –13 Unfortunately, the prevalence of metronidazole resistance in many parts of the world exceeds this. Two surveys from Australia have reported pre‐treatment metronidazole resistance rates of 59–64%, in accord with the findings from this study 2 , .…”

Section: Discussionmentioning

confidence: 64%

“…Initial studies of OAM with the antibiotics taken three times daily for 2 weeks yielded high eradication rates but were not randomized 7 , . 8 A more recent randomized trial of OAM for 1 week reported an overall eradication rate of around 80% in a population with a primary metronidazole resistance rate of 20%; other European reports have been similar 9 , . 10 In the MACH 1 study of 1‐week therapies, an eradication rate of 95% was obtained using OMC, but antibiotic resistance was not determined 11 .…”

Section: Introductionmentioning

confidence: 83%

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Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study

Katelaris

Adamthwaite

Midolo

et al. 2000

Aliment Pharmacol Ther

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 83%

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Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study

Katelaris

Adamthwaite

Midolo

et al. 2000

Aliment Pharmacol Ther

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“…When data from different clinical trials are compared, a higher efficacy of bismuth based triple therapy compared to the same therapy but without the nitroimidazole in nitroimidazole resistant strains is suggested 83 . One study suggested that increasing the dose of a nitroimidazole in resistant strains increases efficacy 84 . Controlled trials, however, are needed to resolve this issue.…”

Section: Clinical Significance Of Nitroimidazole Resistancementioning

confidence: 99%

Review article: nitroimidazole resistance in Helicobacter pylori

Wouden

Thijs

Zwet

et al. 2000

Aliment Pharmacol Ther

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The efficacy of a nitroimidazole‐containing regimen for the treatment of Helicobacter pylori infection is decreased by nitroimidazole resistance. Nitroimidazoles are meta‐ bolized by H. pylori by several nitro‐reductases of which an oxygen‐insensitive NADPH nitroreductase encoded by the rdxA gene is the most important. Null mutations in this gene are associated with resistance. Susceptibility testing to nitroimidazoles may give variable results. This is not only related to the slow growth under specific conditions, but also to variability in the activity of the other nitroreductases and the ability to deactivate toxic metabolites of an NI and to repair DNA damage. Moreover, co‐infections with resistant and susceptible bacteria are frequently found. The presence of nitroimidazole resistance is related to the previous use of this drug. The prevalence of resistance is rising and nowadays 10–50% of the isolates are resistant. Resistance reduces the efficacy of a treatment regimen to a variable degree. This is related to efficacy of the other components of the regimen and the treatment duration. Whether a nitroimidazole is still effective in resistant strains remains unresolved. When nitroimidazole resistance is present, a nitro‐imidazole‐containing regimen should be avoided or a regimen with other highly effective components should be used.

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“…The cure rate was also higher when the duration of treatment increased from 7 to 10 days [28]. As discussed earlier, increasing the dose of metronidazole will sometimes overcome drug resistance and improve cure rates [29].…”

Section: Treatment Duration and Outcomementioning

confidence: 79%

Antibiotic-Resistant H. pylori Infection and its Treatment

Graham

Qureshi²

2000

CPD

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Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm that the infection has been cured 4 to 6 weeks later. Antimicrobial resistance is largely responsible for treatment failures. Resistance to metronidazole can frequently be overcome by increasing the dose and duration of treatment with acid suppression. Clarithromycin is the most effective antibiotic against H. pylori but, unfortunately, resistance to it is increasing and can not be overcome by increasing the dose or duration of therapy with clarithromycin. The choice of therapy should be based on local susceptibility patterns. Re-treatment regimens for treatment failure should exclude antibiotics where acquired resistance is expected (i.e., clarithromycin and possibly metronidazole). Where available, treatment failure should prompt endoscopy and culture and susceptibility testing. Overall, higher doses and longer durations of treatment result in the best cure rates. When multiple treatment regimens fail, salvage therapy regimens such as bismuth or furazolidone quadruple therapy (a bismuth and tetracycline HCl 4 times a day along with a proton pump inhibitor twice a day, and either metronidazole 400 or 500 mg three times daily or furazolidone 100 mg three times daily for 14 days) can be used. Newer agents are needed to cope with the increasing prevalence of antibiotic resistance among H. pylori.

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H. pylori (HP) eradication with omeprazole (O), metronidazole (M) and amoxycillin (a): The impact of drug dosing & resistance on efficacy — The homer story

Cited by 10 publications

References 0 publications

Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study

Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study

Review article: nitroimidazole resistance in Helicobacter pylori

Antibiotic-Resistant H. pylori Infection and its Treatment

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