Interaction of drugs for eradication therapy against antibiotic-resistant strains of Helicobacter pylori.

To clarify the interactions of drugs for combination therapy of Helicobacter pylori infection, especially due to antibiotic-resistant strains, we have evaluated the in vitro effect of combining different drugs. Using a modified time-kill assay, we tested the effect of combining 2 drugs from 4 agents; amoxicillin (AMPC), clarithromycin (CAM), metronidazole (MTZ) and lansoprazole (a proton pump inhibitor). The H. pylori in the study consisted of 4 strains sensitive to the all drugs, 2 strains resistant only to CAM, 2 strains resistant only to MTZ, and 2 strains resistant to both CAM and MTZ. From the 6 different drug combinations, synergism was observed for 5 of the combinations, among which the combination of AMPC and CAM revealed such effects most frequently. However, all of the strains which showed synergism were sensitive to both of the drugs. In the case of the strains resistant to CAM and/or MTZ, no synergism was demonstrated in any of the combinations including CAM and/or MTZ. When a strain was resistant to one drug from a combination, no synergism was detected. Thus, the administration of a drug to which the strains are resistant may have no advantage in the eradication therapy of H. pylori. For a more effective and safer therapy, susceptibility testing should be performed before treatment.