Takayuki Akahane

In Vitro Activities of Rabeprazole, a Novel Proton Pump Inhibitor, and Its Thioether Derivative Alone and in Combination with Other Antimicrobials against Recent Clinical Isolates of Helicobacter pylori

ABSTRACT The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinicalHelicobacter pylori strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole. Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined. Moreover, no apparent antagonistic effect appeared among all of the strains tested.

Susceptibility of Helicobacter pylori Isolates against Agents Commonly Administered for Eradication Therapy and the Efficacy of Chemotherapy

Although chemotherapy has been documented to be effective in the treatment of Helicobacter pylori‐associated gastritis and gastroduodenal ulcers, some cases are known to have been unsuccessful in the attempt to eradicate this species. In this study, we examined the relation between the susceptibility of H. pylori isolates and the efficacy of chemotherapy. We utilized the modified agar plate dilution method to determine the minimum inhibitory concentrations (MICs) of 63 H. pylori strains isolated before treatment with several drugs routinely used during eradication chemotherapy. Among the drugs tested, amoxicillin (AMPC) and clarithromycin (CAM) demonstrated high degrees of activity with MIC90, 0.39 and 0.2 μg/ml, respectively. No highly resistant strain against AMPC was detected among the strains examined, while for CAM and metronidazole (MTZ), 9.5% and 7.9% of the strains, respectively, were resistant before treatment. It should be noted that all of the MICs of the strains from patients with successful therapy were lower than those from patients with unsuccessful therapy. These findings indicate that susceptibility tests should be carried out prior to the commencement of drug administration in order to provide safer and more effective chemotherapy.

Successful Development of Air‐Dried Microplates (HP‐Plates) for Susceptibility Testing against Helicobacter pylori Isolates

We have successfully developed and evaluated a new susceptibility testing procedure against Helicobacter pylori strains using air‐dried microplates “HP‐Plates” containing eight serially‐diluted anti‐H. pylori agents. HP‐Plate wells were reconstituted by the inoculation of 100 μl of H. pylori cell suspensions. After incubation at 37 C for 48 hr under humidified microaerophilic conditions, HP‐Plates were read visually with a circular mirror. We investigated the within‐day reproducibility tests of HP‐Plates using the six quality control (QC) strains we proposed. Of the 20 testings, determining the minimum inhibitory concentrations (MICs) of all the QC strains fell within ± 1 log2 dilution ranges. When 200 clinical isolates were tested with HP‐Plates and compared with the results obtained with the modified broth macrodilution method of NCCLS, more than 90% of the MICs also fell within ±1 log2 dilution ranges. We concluded that the HP‐Plate susceptibility test method is a practical and easily applicable alternative of susceptibility testing for clinical microbiology laboratories in determining the MICs of H. pylori isolates.