Gemifloxacin Can Partially Overcome Quinolone Resistance of <i>H. pylori</i> with <i>gyrA</i> Mutation in Taiwan

Chang, Wei; Kao, Cheng Yen; Wu, Chung Tai; Huang, Angus; Wu, Jiunn Jong; Yang, Hsiao Bai; Cheng, Hsiu Chi; Sheu, Bor Shyang

doi:10.1111/j.1523-5378.2012.00935.x

Cited by 26 publications

(23 citation statements)

References 27 publications

(40 reference statements)

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“…Besides, a cross resistance pattern was observed across different generations of fluoroquinolone (moxifloxacin > levofloxacin > ciprofloxacin > gemifloxacin) with high chance of developing fluoroquinolone resistance as a result of other treatments prior to H. pylori eradication. Similar to an early report on the Taiwanese population [15], the degree of resistance to gemifloxacin was low in the Malaysian population suggested that it may have better drug efficacy than levofloxacin in H. pylori eradication in our population.…”

Section: Discussionsupporting

confidence: 90%

“…As a counter measure, fluoroquinolone-containing triple and bismuth-containing quadruple therapies have also been proposed as second line therapies after the failure of the clarithromycin-containing treatment [12], [13]. In spite of that, a number of studies have shown a low but rapid rise of fluoroquinolone-resistance in countries where fluoroquinolone has been widely prescribed [14], [15], [16], [17], [18], [19]. To date, the mechanisms underlying the resistance to metronidazole, clarithromycin and flouroquinolones remains obscure.…”

Section: Introductionmentioning

confidence: 99%

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Functional and Molecular Surveillance of Helicobacter pylori Antibiotic Resistance in Kuala Lumpur

et al. 2014

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Background Helicobacter pylori is the etiological agent for diseases ranging from chronic gastritis and peptic ulcer disease to gastric adenocarcinoma and primary gastric B-cell lymphoma. Emergence of resistance to antibiotics possesses a challenge to the effort to eradicate H. pylori using conventional antibiotic-based therapies. The molecular mechanisms that contribute to the resistance of these strains have yet to be identified and are important for understanding the evolutional pattern and selective pressure imposed by the environment.Methods and Findings H. pylori was isolated from 102 patients diagnosed with gastrointestinal diseases, who underwent endoscopy at University Malaya Medical Centre (UMMC). The isolates were tested for their susceptibility on eleven antibiotics using Etest. Based on susceptibility test, 32.3% of the isolates were found to have primary metronidazole resistance; followed by clarithromycin (6.8%) and fluoroquinolones (6.8%). To further investigate the resistant strains, mutational patterns of gene rdxA, frxA, gyrA, gyrB, and 23S rRNA were studied. Consistent with the previous reports, metronidazole resistance was prevalent in the local population. However, clarithromycin, fluoroquinolone and multi-drug resistance were shown to be emerging. Molecular patterns correlated well with phenotypic data. Interestingly, multi-drug resistant (MDR) strains were found to be associated with higher minimum inhibitory concentration (MIC) than their single-drug resistant (SDR) counterparts. Most importantly, clarithromycin-resistant strains were suggested to have a higher incidence for developing multi-drug resistance.ConclusionData from this study highlighted the urgency to monitor closely the prevalence of antibiotic resistance in the Malaysian population; especially that of clarithromycin and multi-drug resistance. Further study is needed to understand the molecular association between clarithromycin resistance and multi-drug resistance in H. pylori. The report serves a reminder that a strict antibiotic usage policy is needed in Malaysia and other developing countries (especially those where H. pylori prevalence remained high).

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Functional and Molecular Surveillance of Helicobacter pylori Antibiotic Resistance in Kuala Lumpur

et al. 2014

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“…However, the increase in fluoroquinolone resistance has become a significant limitation for providing effective H. pylori eradication. Newly developed fluoroquinolones, such as gemifloxacin, clinafloxacin, and sitafloxacin, have been studied and demonstrated favorable outcomes for treatment of H. pylori (27). In particular, sitafloxacin has been reported to show outstanding antimicrobial efficacy even for microorganisms with gyrA mutations (28,29).…”

Section: Discussionmentioning

confidence: 99%

High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared with That of Other Fluoroquinolones

Lee

Kim

Nam

et al. 2015

Antimicrob Agents Chemother

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Finafloxacin is a novel fluoroquinolone with improved antimicrobial efficacy, especially in an acidic environment. The efficacy of finafloxacin for the inhibition of Helicobacter pylori infection was compared with the efficacies of levofloxacin and moxifloxacin at neutral and acidic pH. The impacts of gyrA point mutation on the efficacy of those three fluoroquinolones were also investigated. A total of 128 clinical H. pylori strains were utilized. MICs of levofloxacin, moxifloxacin, and finafloxacin were determined at pH 5.0 and pH 7.0 by the agar dilution method. The impact of gyrA point mutations that are responsible for fluoroquinolone resistance was analyzed; the results showed 50 strains with an Asn-87 point mutation, 48 strains with an Asp-91 point mutation, and the remaining 30 strains with no gyrA mutations. The use of finafloxacin led to MIC values at pH 5.0 that were lower than the values seen at pH 7.0 for 112 strains (112/128, 87.5%), and this proportion was higher than that seen with moxifloxacin (21/128, 16.4%, P < 0.001). Finafloxacin also demonstrated a rate of susceptibility (MIC, <1 g/ml) (37.5%, 48/128) at pH 5.0 that was higher than that seen with moxifloxacin (2.3%, 3/128) (P < 0.001). The trends were similar regardless of which of the Asn-87, Asp-91, and A2143 point mutations were present. In conclusion, the superior antimicrobial efficacy of finafloxacin against H. pylori in an acidic environment suggests the possible use of finafloxacin for treatment of H. pylori infection, as has been proposed by its developer, Merlion Pharma. Helicobacter pylori infection is a cause of recurrent peptic ulcer disease, chronic gastritis, and gastric malignancies (1). It has been proven that the eradication of H. pylori can prevent peptic ulcer recurrence (2). However, drug instability and insufficient diffusion to gastric mucosa and mucus in that highly acidic environment require the combination of antibiotics with a proton pump inhibitor (PPI) for H. pylori eradication (3). PPI-clarithromycin-containing triple therapy was the first-line eradication treatment until recently (4). However, as the failure rate of the 7-day triple therapy has increased progressively, sequential or concomitant therapy has come to be used (3, 5). Unfortunately, the 7-day triple therapy is still regarded as the standard primary therapy in South Korea because there is no proven alternative regimen that can provide more efficient and safer eradication (6, 7). The unsatisfactory response of alternative eradication regimens was mainly caused by antimicrobial resistance and was particularly due to clarithromycin resistance (5, 8). Therefore, the Maastricht IV consensus has recommended that PPI-clarithromycin-containing triple therapy without prior susceptibility testing should be avoided when the clarithromycin resistance rate is higher than 15% to 20% (2). Moreover, the current high prevalence of metronidazole resistance in South Korea (9) indicates the necessity of reestablishment of a new standard first-line eradication therapy.In...

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“…One may need to choose a more potent quinolone in order to prevent the development of quinolone resistance during anti- H. pylori therapy. One recent study from Taiwan showed that gemifloxacin was superior to levofloxacin in antimicrobial activity against H. pylori isolates and even overcame some levofloxacin resistance [52]. Gemifloxacin is a powerful potent quinolone against H. pylori .…”

Section: The Impact Of Quinolone Exposure On Tuberculosismentioning

confidence: 99%

Quinolone-Containing Therapies in the Eradication ofHelicobacter pylori

Chuah

Tai

Lee

et al. 2014

BioMed Research International

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Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to “rescue” therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

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Gemifloxacin Can Partially Overcome Quinolone Resistance of H. pylori with gyrA Mutation in Taiwan

Abstract: Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.

Cited by 26 publications

References 27 publications

Functional and Molecular Surveillance of Helicobacter pylori Antibiotic Resistance in Kuala Lumpur

Functional and Molecular Surveillance of Helicobacter pylori Antibiotic Resistance in Kuala Lumpur

High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared with That of Other Fluoroquinolones

Quinolone-Containing Therapies in the Eradication ofHelicobacter pylori

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