Antimicrobial Susceptibility Testing ofHelicobacter pylori in a Large Multicenter Trial: the MACH 2 Study

Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux, France. francis.mé
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 11/1999; 43(11):2747-52.
Source: PubMed


Culture and susceptibility testing of Helicobacter pylori strains was performed in a large multinational, multicenter randomized clinical trial. Culture was carried out on gastric biopsy samples obtained from 516 patients at entry and had a sensitivity of 99% when the [(13)C]urea breath test was used as a reference. Susceptibility testing was performed for clarithromycin and metronidazole on 485 strains by an agar dilution method and the epsilometer test (Etest) and for amoxicillin by an agar dilution method only. Resistance to clarithromycin (>1 microgram/ml) was found in 3% of the H. pylori strains, with a perfect correlation between Etest and agar dilution methods. Resistance to metronidazole (>8 microliter/ml) was found in 27% of the strains by agar dilution, but there were important discrepancies between it and the Etest method. No resistance to amoxicillin was found. The logarithms of the MICs of the three antibiotics against susceptible strains had a distribution close to normal. The impact of resistance was tested in the four arms of the trial. There were not enough clarithromycin-resistant strains to evaluate the impact of resistance on the cure rate of clarithromycin-based regimens. For metronidazole-resistant strains, the impact noted in the clarithromycin-metronidazole arm was partially overcome when omeprazole was added (76% eradication for resistant strains versus 95% for susceptible strains). Secondary resistance to clarithromycin occurred in strains from 12 of 105 patients (11.4%) after the failure of a clarithromycin-based regimen to effect eradication. The detection of point mutations in clarithromycin-resistant strains was performed by a combination of PCR and restriction fragment length polymorphism. Mutations (A2142G and 2143G) were found in all strains tested except one. This study stresses the importance of performing susceptibility tests in clinical trials in order to explain the results of different treatments.

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    • "The cases of H. pylori-related infections are increasing in the developing countries. Triple therapy, consist of a proton pump inhibitor and any of the two antibiotics such as amoxicillin (AMX), clarithromycin (CLA), metronidazole (MNZ) and tetracycline (TET), is commonly utilized to treat H. pylori infections202122. Clinical trials in this aspect have demonstrated an eradication rate of about 80-90% by the use of a relevant triple therapy including AMX [23]. "

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    • "Development of antimicrobial agents for the eradication of multidrug-resistant (MDR) microbes is a challenge for the synthetic chemists [11]. It has been reported that the efficacy of the triple therapy regime is decreasing to unacceptable levels (i.e., ≤80%) [11, 12] due to the antibiotic resistance in H. pylori [11–15]. Almost similar resistance patterns were found in the present research in case of TET and CLA. "
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    • "Plates were incubated in microaerophilic conditions at 37 • C for 72 hrs. The breakpoints used to qualify strains as resistant according to the MIC values were 1 mg/L for both tested antibiotics , as previously described [21] [22]. The determination of MIC values was carried out against the reference H. pylori strain from the American Type Culture Collection, ATCC 43504 Helicobacter pylori, to ensure the quality of susceptibility tests. "
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