sitafloxacin and Helicobacter-Infections

Third generation of quinolones, such as levofloxacin and moxifloxacin, -containing regimens are often used in second-line or rescue treatment of

Topics: Anti-Bacterial Agents; DNA Gyrase; DNA Mutational Analysis; DNA, Bacterial; Drug Resistance, Bacterial; Drug Therapy, Combination; Evidence-Based Medicine; Fluoroquinolones; Gastroenterology; Helicobacter Infections; Helicobacter pylori; Humans; Microbial Sensitivity Tests; Mutation; Proton Pump Inhibitors; Pyrroles; Sulfonamides

Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and third-line treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.

Topics: Anti-Bacterial Agents; Bismuth; Drug Resistance, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Moxifloxacin; Ofloxacin; Rifabutin; Rifamycins; Rifaximin; Salvage Therapy; Virulence Factors

Eradication rates in first-line Helicobacter pylori therapy have been declining over the last decades, mainly due to increasing resistance against the recommended antibiotics clarithromycin and metronidazole. Thus, there is a need to evaluate novel regimens and substances to offer effective alternative treatment strategies. New generation quinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against various Gram-positive and Gram-negative strains and are mostly well tolerated. Based on a large number of studies, quinolones have been introduced in second-line and rescue treatment and are recommended for these indications in current guidelines. Various studies have investigated alternative strategies for first-line treatment including quinolone-based regimens. In the context of increasing resistance rates of Helicobacter pylori against quinolones some risks and benefits have to be considered when using quinolones as a first-line strategy. Besides numerous studies investigating levofloxacin and moxifloxacin there are some promising results for the new substance sitafloxacin, which might overcome primary resistance of Helicobacter pylori against conventional quinolones.

Topics: Anti-Bacterial Agents; Aza Compounds; Drug Resistance, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Ofloxacin; Quinolines

Sitafloxacin (STFX)-containing regimens were shown to be useful options for third-line Helicobacter pylori eradication therapy. It is reported that resistance to quinolone is also increasing globally. Therefore, we conducted an analysis of the current efficacy of a 10-day -STFX-containing third-line rescue therapy and the changes of antibiotic resistance to H. pylori compared to 2 historical controls.. Patients in whom eradication treatment using both first- and second-line triple therapies failed were enrolled from 2014 to 2015. The minimum inhibitory concentrations of STFX, clarithromycin (CLR), amoxicillin (AMX), metronidazole (MTZ) and the gyrA mutation status of the H. pylori strains were determined before treatment. After that, the patients received a 10-day triple therapy containing esomeprazole (20 mg, b.i.d.), AMX (500 mg, q.i.d.) and STFX (100 mg, b.i.d.; 10-day EAS). The eradication rate and the rate of antibiotic resistance to H. pylori were compared with 2 previous reports about STFX-containing third-line rescue therapies in 2009-2011 and 2012-2013. To explore the association between the eradication rates of regimens containing STFX, AMX and proton pump inhibitors and the location of gyrA mutation or AMX resistance, a meta-analysis was attempted.. The overall eradication rates, the eradication rate for gyrA mutation negative- and positive- strains were 81.6% (31/38), 94.7% (18/19) and 68.4% (13/19) respectively. These rates were not significantly different from 2 previous reports. The resistant rates to STFX, CLR, AMX, MTZ and the rate of presence of mutation in gyrA were 50.0, 81.6, 36.8, 78.9 and 50.0%, respectively, which was also not significantly different from 2 previous reports. A meta-analysis showed that the relative risk of the eradication failure is significantly lower in gyrA mutation negative strains compared to gyrA mutation positive strains, and that the relative risk of the eradication failure is significantly lower in gyrA mutation at D91 compared to gyrA mutation at N87 (p < 0.001 and p = 0.022, respectively). Moreover, a meta-analysis showed that the relative risk of the eradication failure is significantly lower in AMX-sensitive strains compared to AMX-resistant ones.. Changes in the rate of antibiotic resistance to H. pylori were not observed from 2009 to 2015. The status of gyrA mutation is a superior marker for predicting successful eradication in STFX/AMX-containing triple regimen as a third-line rescue therapy.

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; DNA Gyrase; Drug Resistance, Bacterial; Drug Therapy, Combination; Esomeprazole; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome

Sitafloxacin-containing Helicobacter pylori eradication therapy is a promising third-line therapeutic approach, but there is no previous studies between gyrA mutation status of H. pylori strains and the efficacy of 10-day sitafloxacin-containing regimens. Here, we assessed the efficacy of 2 different 10-day sitafloxacin-containing rescue regimens.. Patients who failed first- and second-line eradication therapies were enrolled. The minimum inhibitory concentrations (MICs) of sitafloxacin, amoxicillin, and metronidazole and the gyrA mutation status of the H. pylori strains were determined before treatment. The patients were randomized to receive a 10-day triple therapy containing either esomeprazole (20 mg, b.i.d.), amoxicillin (500 mg, q.i.d.), and sitafloxacin (100 mg, b.i.d.) (EAS regimen) or esomeprazole (20 mg, b.i.d.), metronidazole (250 mg, b.i.d.), and sitafloxacin (100 mg, b.i.d.) (EMS regimen). Eradication rates were evaluated by the [13C] urea breath test or the H. pylori stool antigen test.. All patients with gyrA mutation-negative strains (24 in EAS and 16 in EMS) showed successful eradication, irrespective of the regimen they received. In patients with gyrA mutation-positive strains, we found eradication rates of 70.3% (26/37) and 66.7% (26/39) in the EAS and EMS groups in per-protocol population, respectively (p = .81). According to logistic regression analyses, the MICs of sitafloxacin, which were strongly associated with gyrA mutation status, were independently associated with successful eradication in both groups. This study was registered in the UMIN Clinical Trials Registry as UMIN000006483.. There is no significant difference in the eradication rates between EAS and EMS, regardless of the gyrA mutation status of the H. pylori strains. GyrA mutation status was an important factor in predicting successful eradication with sitafloxacin-containing rescue therapies.

Topics: Adult; Aged; Anti-Bacterial Agents; DNA Gyrase; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutant Proteins; Prospective Studies; Salvage Therapy; Treatment Outcome

Quinolone-based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin-based eradication regimens as rescue for the eradication of H. pylori.. We attempted to eradicate H. pylori in 180 Japanese patients who had never failed in eradication of H. pylori with the triple proton pump inhibitor/amoxicillin/clarithromycin therapy (1st line) and the triple proton pump inhibitor/amoxicillin/metronidazole therapy (2nd line). They were assigned to either the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., amoxicillin 500 mg q.i.d, and sitafloxacin 100 mg b.i.d. (RAS) for 1 or 2 weeks or the triple therapy with rabeprazole 10 mg b.i.d./q.i.d., metronidazole 250 mg b.i.d., and sitafloxacin 100 mg b.i.d. (RMS) for 1 or 2 weeks. Eradication was assessed via the (13) C-urea breath test and rapid urease test.. Intention-to-treat and per-protocol analyses of eradication rates were 84.1% (37/44) and 86.4% (37/43) with RAS for 1 week, 88.9% (40/45) and 90.9% (40/44) for RAS for 2 weeks, 90.9% (40/44) and 90.9% (40/44) for 1 week-RMS and 87.2% (41/47) and 91.1% (41/45) with RMS for 2 weeks. We noted no statistical significant differences in eradication rates among four regimens.. All of the above-described rescue regimens proved relatively equally useful in the eradication of H. pylori. Of them, RAS for 2 weeks and RMS for 1 or 2 weeks could attain the rescue eradication rates higher than 90% by per-protocol analysis.

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Aryl Hydrocarbon Hydroxylases; Clarithromycin; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Female; Fluoroquinolones; Gastritis; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Rabeprazole; Time Factors; Treatment Outcome

The present study sought to establish a standard third-line eradication regimen for Helicobacter pylori in Japan.. Subjects were 204 patients with H. pylori infection in whom the standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX.. Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %; p < 0.05) and the LAL group (43.1 %; p < 0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX.. The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for H. pylori in Japan.

Topics: Aged; Amoxicillin; Anti-Ulcer Agents; Drug Resistance; Drug Therapy, Combination; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Lansoprazole; Levofloxacin; Male; Middle Aged; Treatment Outcome

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.

Topics: Amoxicillin; Anti-Bacterial Agents; Disease Eradication; DNA Gyrase; Drug Resistance, Bacterial; Female; Fluoroquinolones; Genes, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Inhibitory Concentration 50; Japan; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Pepsinogen A; Pepsinogen C; Prospective Studies

Nepal and Bangladesh have a high prevalence of. We used the agar dilution method to determine the minimal inhibitory concentration of 5 alternative antibiotics against 42 strains from Nepal and 56 from Bangladesh and performed whole genome mutation analysis.. No resistance to furazolidone or rifabutin and a high susceptibility of sitafloxacin (95.2% in Nepal and 98.2% in Bangladesh) were observed. In contrast, resistance to rifaximin (52.4% in Nepal and 64.3% in Bangladesh) was high. Moreover, resistance to garenoxacin was higher in Bangladesh (51.6%) than in Nepal (28.6%,. Rifabutin can be cautiously implemented as therapy for

Topics: Anti-Bacterial Agents; Bangladesh; DNA Gyrase; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Female; Fluoroquinolones; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Male; Microbial Sensitivity Tests; Mutation; Nepal; Rifabutin; Whole Genome Sequencing

The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition.. To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain.. We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a. Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen.. In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q.i.d. and an antibiotic agent (amoxicillin q.i.d. or sitafloxacin b.i.d.) in Japanese patients with metronidazole-resistant strains.

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Drug Resistance, Bacterial; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Hospitals, University; Humans; Japan; Male; Metronidazole; Middle Aged; Proton Pump Inhibitors; Rabeprazole; Retrospective Studies; Treatment Outcome

To examine the efficacy of third-line Helicobacter pylori eradication therapy with esomeprazole, amoxicillin, and sitafloxacin for patients with clarithromycin- and metronidazole-based first- and second-line therapy failure.. Thirty patients with first- and second-line H. pylori eradication failure were treated prospectively with esomeprazole 20mg twice daily, amoxicillin 750mg twice daily, and sitafloxacin 100mg twice daily for 7 days. After 8-12 weeks, the outcome of eradication therapy was assessed by. All 30 patients completed the study. Eradication was successful in 25 patients and the eradication rate was 83% in the intention-to-treat and per-protocol analyses. No specific or significant adverse events were recorded in the 30 patients. Patient characteristics such as sex, body mass index, and pepsinogen I/II ratio did not differ between patients who were treated successfully and those who were not treated successfully.. Third-line H. pylori eradication therapy with esomeprazole, amoxicillin, and sitafloxacin is as safe and effective as previously reported sitafloxacin-based triple therapy.

Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Esomeprazole; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Metronidazole; Middle Aged; Prospective Studies; Treatment Outcome

A 74-year-old woman undergoing outpatient follow-up for reflux esophagitis and atrophic gastritis tested positive for Helicobacter pylori and underwent primary eradication therapy with lansoprazole (LPZ) 30 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200 mg twice daily for 1 week in August 2012. A urea breath test (UBT) after this treatment revealed that eradication had failed. Secondary eradication therapy was carried out with esomeprazole (EPZ) 20 mg, AMPC 750 mg, and metronidazole (MNZ) 250 mg twice daily for 1 week, but this also failed. The third attempt at eradication consisted of EPZ 20 mg, AMPC 750 mg, and sitafloxacin (STFX) 100 mg twice daily for 1 week, but this also ended in failure. A fourth attempt using rabeprazole (RPZ) 20 mg (4 times daily) with MNZ 250 mg and STFX 100 mg twice daily for 2 weeks also failed, as did a fifth attempt in April 2015 using vonoprazan (VPZ) 20 mg, AMPC 750 mg, and MNZ 250 mg twice daily for 1 week. Eradication was finally successful after the sixth attempt, in which the patient was treated with vonoprazan 20 mg, MNZ 250 mg, and STFX 100 mg twice daily for 2 weeks.

Topics: Aged; Drug Therapy, Combination; Female; Fluoroquinolones; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Pyrroles; Sulfonamides; Treatment Failure; Treatment Outcome

Bacterial resistance of Helicobacter pylori to antibiotics is increasing and it often leads to failure of antibiotic treatment. A new sitafloxacin-based triple therapy was developed to counter this situation; the fluoroquinolone sitafloxacin has a low minimum inhibitory concentration for H. pylori.. To investigate the efficacy in Japanese patients of sitafloxacin-based triple therapy and document its efficacy in relation to anti-microbial susceptibility.. We investigated the efficacy of a 1-week sitafloxicin-based regimen of rabeprazole 10 mg four times daily (q.d.s.), metronidazole 250 mg twice daily (b.d.) and sitafloxacin 100 mg b.d. in 180 H. pylori-positive Japanese patients (first-line treatment: n = 45, second-line; n = 41, third-line: n = 94). At 8 weeks, patients were given the (13) C-urea breath test to assess eradication status.. Eradication rate was 92.2% [95% confidence interval (CI): 87.3-95.7%, 166/180] in intention-to-treat analysis. Although the eradication rate was higher in patients treated with first-line therapy [45/45 (100%, 95% CI: 83.4-100%)] than in those with second- [38/41 (92.7%, 80.1-98.5%)] or third-line therapy [83/94 (88.3%, 80.0-94.0%)], no significant differences were noted with respect to the number of previous therapy attempts (P = 0.054). Eradication rates in patients infected with sensitive- and resistant strains to metronidazole were 96.6% (28/29) and 96.3% (77/80) (P = 0.941), respectively, while rates were 98.4% (60/61) in sitafloxacin-sensitive and 50.0% (1/2) in sitafloxacin resistant strains (P < 0.001).. Sitofloxacin-based triple therapy with metronidazole b.d. and rabeprazole q.d.s. achieved an eradication rate exceeding 88%, irrespective of eradication history, CYP2C19 genotype, or metronidazole resistance status.

Topics: Adult; Aged; Anti-Bacterial Agents; Breath Tests; Drug Therapy, Combination; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Rabeprazole

Eradication of H. pylori in patients allergic to penicillin should be performed using regimens without penicillin derivatives. We treated a total of 28 patients allergic to penicillin with a proton pump inhibitor (PPI), metronidazole (250 mg bid) and sitafloxacin (100 mg bid) for one to two weeks. At four to eight weeks after the treatment, the patients underwent the [(13)C]-urea breath test. The overall eradication rate was 100.0%. Mild adverse events were observed. Triple therapy with a PPI, metronidazole and sitafloxacin is well tolerated and effective for the eradication of H. pylori in patients allergic to penicillin.

Topics: Anti-Bacterial Agents; Breath Tests; Cytochrome P-450 CYP2C19; Drug Administration Schedule; Drug Hypersensitivity; Drug Therapy, Combination; Female; Fluoroquinolones; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Metronidazole; Middle Aged; Penicillins; Proton Pump Inhibitors; Retrospective Studies; Treatment Outcome

Sitafloxacin-based triple therapy achieved 83.6% (per-protocol) and 78.2% (intention-to-treat) success in eradicating Helicobacter pylori among 78 Japanese patients after clarithromycin-based first-line and metronidazole-based second-line triple therapies failed. Eradication succeeded in 32 out of 43 patients, even with gyrA mutation-positive Helicobacter pylori (per protocol). The position of the gyrA mutation (N87 or D91) was determined to be a better marker than MIC levels for predicting outcomes of sitafloxacin-based treatment.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; Biomarkers, Pharmacological; Clarithromycin; DNA Gyrase; Female; Fluoroquinolones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Mutation; Treatment Failure

A total of 293 strains of Helicobacter pylori, including strains resistant to levofloxacin, clarithromycin, metronidazole, or amoxicillin, were examined for in vitro susceptibility to 10 antimicrobial agents. Among these agents, sitafloxacin (a fluoroquinolone) showed the greatest activity (MIC(90), 0.06 μg/ml), with high bactericidal activity and synergy in sitafloxacin-lansoprazole (a proton pump inhibitor) combination. In a Mongolian gerbil model with a H. pylori ATCC 43504 challenge, marked eradication effects were observed at ≥1 mg/kg for sitafloxacin, ≥10 mg/kg for levofloxacin, and ≥10 mg/kg for lansoprazole, reflecting MIC levels for each agent (0.008, 0.25, and 2 μg/ml, respectively). The therapeutic rates were 83.3% for the sitafloxacin (0.3 mg/kg)-lansoprazole (2.5 mg/kg) combination and 0% for either sitafloxacin or lansoprazole alone. The maximum serum concentration (C(max)) of sitafloxacin was 0.080 ± 0.054 μg/ml at 30 min, when orally administered at 1 mg/kg. The simultaneous administration of lansoprazole resulted in no difference. In the resistance development assay, MICs of levofloxacin increased 64- to 256-fold with gyrA mutations (Ala88Pro and Asn87Lys), while MICs of sitafloxacin only up to 16-fold with the Asn87Lys mutation. The data suggest that sitafloxacin exhibited superior anti-H. pylori activity with low rates of resistance development in vitro and that, reflecting high in vitro activities, sitafloxacin-lansoprazole combination exhibited strong therapeutic effects in Mongolian gerbils with a C(max) of sitafloxacin that was 10-fold higher than the MIC value at a 1-mg/kg administration.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Bacterial Agents; Drug Combinations; Fluoroquinolones; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Lansoprazole; Levofloxacin; Male; Microbial Sensitivity Tests; Ofloxacin