Objective. To evaluate the efficacy of two commonly employed treatments for Helicobacter pylori infection and the impact of bacterial resistance to antibiotics on eradication rate.



Methods. Ninety-two consecutive H. pylori-positive patients with active peptic ulcer disease were randomly enrolled to receive a 7-day treatment with either lansoprazole 30 mg plus amoxicillin 1 g and clarithromycin 500 mg [all twice a day (b.i.d.), Group A, n = 46]; or bismuth subcitrate 125 mg four times a day (q.i.d.) plus tetracycline 500 mg q.i.d and furazolidone 200 mg b.i.d. (Group B, n = 46) H. pylori status was reassessed 30 days after completion of the therapy and bacterial resistance to the antibiotics was investigated using an in vitro assay.



Results. Five patients from each study group were lost to follow up. Both treatments resulted in similar H. pylori eradication rate: 66–60% (per protocol), 59–52% (intention-to-treat) in Groups A and B, respectively (non significant). However, eradication improved to 79% in the absence of H. pylori resistance to clarithromycin or amoxicillin.



Conclusion. Primary resistance to clarithromycin or amoxicillin may underscore a potentially serious problem for the eradication of H. pylori infection. Testing for bacterial resistance may become necessary to improve therapeutic efficacy.

Increased primary resistance to recommended antibiotics negatively affects Helicobacter pylori eradication.

Bismuth compounds remain useful for Helicobacter pylori eradication therapy. These include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and, most recently, ranitidine bismuth citrate (RBC). CBS appears to prevent the development of imidazole resistance when coadministered with nitroimidazoles. Traditional triple therapy with bismuth, metronidazole and tetracycline or amoxicillin (BMT/A) only partially overcomes metronidazole resistance. However, the addition of a PPI to bismuth triple therapy largely overcomes established metronidazole resistance if treatment is given for at least one week or more. When RBC rather than PPI is used with clarithromycin, this dual regimen appears to be more effective in preventing the development of secondary clarithromycin resistance. The triple combination of RBC, metronidazole and clarithromycin appears to be effective against metronidazole resistant strains of H pylori. Thus, overall, there is some evidence that bismuth compounds may prevent the development of antibiotic resistance and that existing antibiotic resistance may at least be partially overcome in vitro and in vivo. With the growing emergence of H pylori resistance to metronidazole and clarithromycin, further research to clarify the role of bismuth compounds is required.

/pdf/effects-of-in-vitro-antibiotic-resistance-on-treatment-sdku6z2c1a.pdf

Effects of in vitro antibiotic resistance on treatment: Bismuth-containing regimens

Towards the ideal regimen for Helicobacter pylori eradication: the search continues.

AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug out-pumping during Helicobacter pylori (H pylori) infection treatment with classic antibiotic therapy.

METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. The H pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF).

RESULTS: Upon the first cycle, H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P<0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P<0.0001) in patients with multiple therapeutic failure than in those with successful H pylori eradication and control subjects.

CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.

Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection.

P-glycoprotein is important in local antibiotic resistance. Aim was to evaluate the role of P-glycoprotein in local antibiotic resistance in patients with antral gastritis during antibiotic therapy to Helicobacter pylori infection. In the group of 53 patients with pathohistologically verified gastritis and microbiologically confirmed H. pylori infection (no signs of antimicrobial resistance) we have determined P-glycoprotein activity in gastric mucosa biopsy specimens, and compared them with the P-glycoprotein activity in 12 control subjects with normal endoscopic findings. The H. pylori positive patients were treated according to Maastricht protocol with short-term 7-day therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor P-glycoprotein activity was determined in rhodamine dye efflux test and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. H. pylori was successfully eradicated in the first cycle in 20 patients, whereas therapy was continued in 33 patients. The mean pre-treatment RMF values were higher in patients with H. pylori infection then in control subjects (p < 0.0046). RMF was also higher in patients with multiple therapeutic failure than in those with successful H. pylori eradication (p < 0.0001). RMF increased significantly during the antibiotic therapy (p < 0.05). P-glycoprotein might be one of the causes of therapy failure in patients with H. pylori. Our study confirms the importance of quantitative evaluation of P-glycoprotein expression during antibiotic treatment response.

/pdf/the-importance-of-p-glycoprotein-multidrug-transporter-lp2lbm2ddf.pdf

The Importance of P-glycoprotein Multidrug Transporter Activity Measurement in Patients with Helicobacter pylori Infection

Drug Therapy of Helicobacter pylori Infection: A Meta-Analysis

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Drug Therapy of Helicobacter pylori Infection: A Meta-Analysis