Sitafloxacin Activity against Helicobacter pylori Isolates, Including Those with gyrA Mutations

Abstract

Sitafloxacin showed MICs of less than or equal to 0.5 g/ml against 105 isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times, respectively, higher than the highest MICs observed for sitafloxacin.The guidelines for the management and treatment of Helicobacter pylori infections established by the European Helicobacter Study Group Third Masstricht Consensus Report recommend an eradication antimicrobial chemotherapy consisting of amoxicillin, clarithromycin, and a proton pump inhibitor alone or in combination with metronidazole and clarithromycin (10). On the other hand, a trend toward increased clarithromycin resistance in Japan has been reported (8); furthermore, high metronidazole resistance rates associated with H. pylori eradication failure have been seen in the United States, Europe, and Asia with the exception of Japan (11). In the search for alternative eradication treatment regimens, it has been recently reported in the United States and Europe that levofloxacin may be efficacious in H. pylori eradication therapy (7, 13). At the same time, the increased use of levofloxacin-based eradication regimens has led to increasing resistance to levofloxacin in H. pylori as a result of mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene correlating with the decreased effectiveness of levofloxacin in eradication regimens (16). Sitafloxacin is a recently developed fluoroquinolone with wide-spectrum activity, ranging from gram-positive cocci to gram-negative bacilli (1, 15). We studied the effect of mutations in the gyrA gene and its impact on the antimicrobial activity of sitafloxacin in H. pylori.(This study was presented at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 25 to 28 October 2008.)A total of 105 H. pylori isolates were recovered from the gastric mucosa of patients presenting with gastroduodenal diseases in health care facilities in Japan between 2004 and 2005. Of the 105 patients, 57 (54.3%) were males and 48 (45.7%) were females, and the average age was 57.9 years (range in age from 21 to 84). None of the patients had previously undergone eradication therapy. The spectrum of peptic ulcers included 39 (37.1%) cases of chronic gastritis, 21 (20.0%) gastric ulcers, 18 (17.1%) duodenal ulcers, 9 (8.6%) gastric cancers, 8 (7.6%) gastroduodenal ulcers, and 10 (9.5%) cases with other causes or an unspecified diagnosis. Only one isolate per patient was included among the 105 isolates.Susceptibilities to sitafloxacin (Daiichi Sankyo, Japan), garenoxacin [a novel des-fluoro(6)quinolone (Astellas, Japan) (6)], and levofloxacin (Daiichi Sankyo, Japan) were determined by agar dilution method according to CLSI guidelines by using drugs with known potency (4, 5). The agar dilution method was performed by serial twofold dilution on MuellerHinton agar (Becton Dickinson, MD) with 5% sheep blood using 1 to 3 l of a McFarland 2.0-adjusted inoculum and

Sitafloxacin resistance in Helicobacter pylori isolates and sitafloxacin-based triple therapy as a third-line regimen in Japan

“…However, it has been reported that the prevalence of LVX-resistant H. pylori is increasing in several regions and countries [4,5,8,12,13]. In Japan, Matsumoto et al [14] reported that the resistance of H. pylori strains to LVX was 14.2% in cases of CLR-based treatment failure in 2005, but we and others [11] recently found that almost 40% of strains in eradication-naive patients showed LVX MICs of ≥2.0 g/mL, indicating that LVX-resistant H. pylori is increasing. Thus, LVX-based triple therapy might be less effective in our study population as well as in regions with a high prevalence of LVX-resistant H. pylori.…”

“…All rights reserved. doi:10.1016/j.ijantimicag.2011.12.002 mutations [10,11]. In this study, the susceptibility of clinical isolates of H. pylori to STX was evaluated and the efficacy of STX-based triple therapy as a third-line H. pylori eradication regimen was examined.…”

Eradication of <i>H. pylori</i> Infection in Patients Allergic to Penicillin Using Triple Therapy with a PPI, Metronidazole and Sitafloxacin

“…In this study, 60.0% of the patients were infected with levofloxacin-resistant strains of H. pylori. However, sitafloxacin is reported to have a lower MIC than levofloxacin and to be effective in patients infected with strains with mutations in gyrA, a genetic marker for resistance to levofloxacin (8,14). Therefore, in the present study, we used sitafloxacin in patients allergic to penicillin derivatives.…”

“…Recently, sitafloxacin, a fluoroquinolone, has become clinically available in Japan and is reported to have a lower minimum inhibitory concentration (MIC) for H. pylori (8). Researchers have used sitafloxacin in patients allergic to penicillin with metronidazole and a PPI since 2008 and reported excellent eradication rates.…”

Current recommendations forHelicobacter pyloritherapies in a world of evolving resistance

“…66 Beside levofloxacin, moxifloxacin has also been used successfully, 67 but it is now recommended to limit the use of this drug in several countries due to various adverse events. There are promising data from Japan especially with sitafloxacin, a fluoroquinolone with higher efficacy especially in case of resistance associated mutations 68 and active at acidic pH. In a large multicenter trial in Japan, in patients receiving a third-line therapy in antibiotic in areas of known high resistance.…”