A systematic review of <i>Helicobacter pylori</i> eradication therapy—the impact of antimicrobial resistance on eradication rates

Houben,; Beek, Diederik van de; Hensen,; Craen, Anton J. M. de; Rauws,; Tytgat,

doi:10.1046/j.1365-2036.1999.00555.x

Cited by 311 publications

(284 citation statements)

References 39 publications

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“…Trichomonas vaginalis, Entamoeba histolytica, Enterococcus species, Giardia lamblia, Clostridium species, and Bacteroides (1)(2)(3)(4) and is also a critical ingredient of modern multidrug therapies for Helicobacter pylori eradication regimes used to control ulcers (5). The mode of action for the 5-Ni antibiotics, as illustrated in Fig.…”

Section: Dimetridazole (Dmz) and Tinidazole (Tnz) Mtr Is Extensivelmentioning

confidence: 99%

Structural Basis of 5-Nitroimidazole Antibiotic Resistance

Leiros¹,

Kozielski-Stuhrmann²,

Kapp

et al. 2004

Journal of Biological Chemistry

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5-Nitroimidazole-based antibiotics are compounds extensively used for treating infections in humans and animals caused by several important pathogens. They are administered as prodrugs, and their activation depends upon an anaerobic 1-electron reduction of the nitro group by a reduction pathway in the cells. Bacterial resistance toward these drugs is thought to be caused by decreased drug uptake and/or an altered reduction efficiency. One class of resistant strains, identified in Bacteroides, has been shown to carry Nim genes (NimA, -B, -C, -D, and -E), which encode for reductases that convert the nitro group on the antibiotic into a non-bactericidal amine. In this paper, we have described the crystal structure of NimA from Deinococcus radiodurans (drNimA) at 1.6 Å resolution. We have shown that drNimA is a homodimer in which each monomer adopts a ␤-barrel fold. We have identified the catalytically important His-71 along with the cofactor pyruvate and antibiotic binding sites, all of which are found at the monomer-monomer interface. We have reported three additional crystal structures of drNimA, one in which the antibiotic metronidazole is bound to the protein, one with pyruvate covalently bound to His-71, and one with lactate covalently bound to His-71. Based on these structures, a reaction mechanism has been proposed in which the 2-electron reduction of the antibiotic prevents accumulation of the toxic nitro radical. This mechanism suggests that Nim proteins form a new class of reductases, conferring resistance against 5-nitroimidazole-based antibiotics.Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is important for efficient treatment of bacterial infections. One important class of antibiotics, the 5-nitroimidazole (5-Ni) 1 drug derivatives, includes metronidazole (MTR), dimetridazole (DMZ), and tinidazole (TNZ). MTR is extensively used in the treatment of anaerobic infections caused by Trichomonas vaginalis, Entamoeba histolytica, Enterococcus species, Giardia lamblia, Clostridium species, and Bacteroides (1-4) and is also a critical ingredient of modern multidrug therapies for Helicobacter pylori eradication regimes used to control ulcers (5). The mode of action for the 5-Ni antibiotics, as illustrated in Fig. 1, has been shown to be similar in different pathogens (6 -8). The inactive prodrug enters cells by simple diffusion and is then reduced in a 1-electron reduction into the toxic compound, the short-lived radical anion R-N⅐O 2 Ϫ . This reaction is mediated by ferredoxin, which receives an electron from the pyruvate-ferredoxin oxidoreductase (PFOR) complex via conversion of pyruvate to acetyl coenzyme A (9). The resulting nitro radical anion probably causes DNA strand breaks, DNA helix destabilization, unwinding of DNA, and finally cell death (1, 2, 10, 11), and damage to other vital cell systems is also possible (6).The success of such drugs depends on the reductive activation of the nitro group on the 5-Ni drug, which ...

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Section: Dimetridazole (Dmz) and Tinidazole (Tnz) Mtr Is Extensivelmentioning

confidence: 99%

Structural Basis of 5-Nitroimidazole Antibiotic Resistance

Leiros¹,

Kozielski-Stuhrmann²,

Kapp

et al. 2004

Journal of Biological Chemistry

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“…Production of biofilm by H. pylori has important effect in promoting its resistance to antimicrobials and host defense factors [40]. It is generally accepted that the H. pylori dormant states of coccoid forms can survive for a long time in the gastric environment.…”

Section: Discussionmentioning

confidence: 99%

Effect of Alginate Lyase on Biofilm-GrownHelicobacter pyloriProbed by Atomic Force Microscopy

Maiorana

Bugli

Papi

et al. 2015

International Journal of Polymer Science

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Helicobacter pylori (H. pylori) is a microorganism with a pronounced capability of adaptation under environmental stress solicitations. Its persistence and antimicrobial resistance to the drugs commonly used in the anti-H. pylori therapy are associated with the development of a biofilm mainly composed of DNA, proteins, and polysaccharides. A fundamental step to increase the success of clinical treatments is the development of new strategies and molecules able to interfere with the biofilm architecture and thus able to enhance the effects of antibiotics. By using Atomic Force Microscopy and Scanning Electron Microscopy we analyzed the effects of the alginate lyase (AlgL), an enzyme able to degrade a wide class of polysaccharides, on the H. pylori shape, surface morphology, and biofilm adhesion properties. We demonstrated that AlgL generates a noticeable loss of H. pylori coccoid form in favor of the bacillary form and reduces the H. pylori extracellular polymeric substances (EPS).

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“…The higher rates of metronidazole resistance in Brazil can be due its widespread use in gynecological infections and parasitic diseases like giardiasis and amebiasis (27) . In a review of all available data in the literature including 770 studyarms, HOUBEN et al (10) observed that in the case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuthbased triple and proton pump inhibitor-based triple therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, caution is required when using the 1.5 g/day dosage owing to the risk of severe, life-threatening pseudomembranous colitis, particularly in the elderly (28) . One-week low-dose clarithromycin (250 mg bid) combinations with PPIs and tinidazole or metronidazole have also been tested and have achieved impressive (93%-95%) eradication rates (10,15,16) . However, the 30%-40% prevalence of metronidazoleresistant Hp strains in the United Kingdom, Belgium, Finland, and other industrialized countries (9,17,31) casts doubt on the reproducibility of such results in the general population.…”

Section: Discussionmentioning

confidence: 99%

The impact of Helicobacter pylori resistance on the efficacy of a short course pantoprazole based triple therapy

Eisig¹,

André²,

Silva³

et al. 2003

Arq. Gastroenterol.

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-Background -Many of the currently used Helicobacter pylori eradication regimens fail to cure the infection due to either antimicrobial resistance or poor patient compliance. Those patients will remain at risk of developing potentially severe complications of peptic ulcer disease. Aim -We studied the impact of the antimicrobial resistance on the efficacy of a short course pantoprazole based triple therapy in a single-center pilot study. Methods -Forty previously untreated adult patients (age range 20 to 75 years, 14 males) infected with Helicobacter pylori and with inactive or healing duodenal ulcer disease were assigned in this open cohort study to 1 week twice daily treatment with pantoprazole 40 mg, plus clarithromycin 250 mg and metronidazole 400 mg. Helicobacter pylori was assessed at entry and 50 ± 3 days after the end of treatment by rapid urease test, culture and histology of gastric biopsies. The criteria for eradication was a negative result in the tests. Susceptibility of Helicobacter pylori to clarithromycin and metronidazole was determined before treatment with the disk diffusion test. Results -One week treatment and follow up were complete in all patients. Eradication of Helicobacter pylori was achieved in 35/40 patients (87.5%) and was higher in patients with nitroimidazole-susceptible strains [susceptible: 20/20 (100%), resistant: 10/ 15 (67%)]. There were six (15%) mild adverse events reports. Conclusions -A short course of pantoprazole-based triple therapy is well tolerated and effective in eradicating Helicobacter pylori. The baseline metronidazole resistance may be a significant limiting factor in treatment success.

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A systematic review of Helicobacter pylori eradication therapy—the impact of antimicrobial resistance on eradication rates

Cited by 311 publications

References 39 publications

Structural Basis of 5-Nitroimidazole Antibiotic Resistance

Structural Basis of 5-Nitroimidazole Antibiotic Resistance

Effect of Alginate Lyase on Biofilm-GrownHelicobacter pyloriProbed by Atomic Force Microscopy

The impact of Helicobacter pylori resistance on the efficacy of a short course pantoprazole based triple therapy

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