Sitafloxacin resistance in Helicobacter pylori isolates and sitafloxacin-based triple therapy as a third-line regimen in Japan.
The third-line treatment regimen for Helicobacter pylori after failure of clarithromycin- and metronidazole-based therapies is not yet established. Sitafloxacin (STX) is a quinolone that possesses potent in vitro activity against H. pylori. In this study, the susceptibility of H. pylori isolates to STX was examined and the efficacy of STX-based triple therapy as a third-line regimen was evaluated. STX showed minimum inhibitory concentrations (MICs) of ≤1 μg/mL against all 100 H. pylori isolates, and the MIC(90) (MIC for 90% of the organisms) of STX was 5 log(2) dilutions lower than that of levofloxacin (LVX). The MIC(50) (MIC for 50% of the organisms) of STX against gyrA mutants was 0.12 μg/mL and was significantly lower than that of LVX (8 μg/mL). The activity of STX at pH 5.5 was significantly less than that at pH 7.0. In the clinical trial, 28 patients with two eradication failures were treated with STX-based triple therapy [rabeprazole 10 mg twice daily (b.i.d.), amoxicillin 750 mg b.i.d. and STX 100mg b.i.d. for 7 days]. The eradication rate was 75% using intention-to-treat analysis and 80% using per-protocol analysis. Two gyrA mutant strains were eradicated. Amongst participants, a low pepsinogen I/II ratio was associated with successful eradication. These results suggest that STX could be active against most clinical H. pylori isolates and that STX-based triple therapy is a promising and safe third-line therapy.
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. hiratay-int@h.u-tokyo.ac.jp
Yoshihiro
Y
Hirata
Tomoya
T
Ohmae
Ayako
A
Yanai
Kosuke
K
Sakitani
Yoku
Y
Hayakawa
Shuntaro
S
Yoshida
Takafumi
T
Sugimoto
Yuzo
Y
Mitsuno
Masao
M
Akanuma
Yutaka
Y
Yamaji
Keiji
K
Ogura
Shin
S
Maeda
Kazuhiko
K
Koike
D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D027081:DNA Gyrase / Q000235:genetics; D060740:Disease Eradication / Q000379:methods; D024881:Drug Resistance, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology* / Q000627:therapeutic use; D005798:Genes, Bacterial; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007564:Japan / Q000453:epidemiology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D020116:Pepsinogen A / Q000737:chemistry; D020115:Pepsinogen C / Q000737:chemistry; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D020115:Pepsinogen C; D000658:Amoxicillin; D020116:Pepsinogen A; C076246:sitafloxacin; D027081:DNA Gyrase