Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA

Kim, So-Yeong; Joo, Young Min; Lee, Hak Sung; Chung, In Sik; Yoo, Yun‐Jung; Merrell, D. Scott; Heon, Jeong

doi:10.1038/ja.2008.6

Cited by 28 publications

(22 citation statements)

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“…The most commonly used treatments include bismuth salts, H2 receptor antagonists and proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole. Amoxycillin, tetracycline, metronidazole and clarithromycin are the most effective therapies for this infection (11)(12)(13). Meanwhile, the treatment of H. pylori infection does not always eradicate the organism.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Resistance of Helicobacter pylori Strains to Selected Antibiotics in Isfahan, Iran

Mirzaei

Poursina

Faghri

et al. 2013

Jundishapur J Microbiol

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Background:Helicobacter pylori (H. pylori) is one of the most common infectious diseases in the world. It colonizes about 50-60% of the world's population. The estimated prevalence of H. pylori infection is approximately 65% in Iran. Objectives: The aim of the present study was to investigate the antimicrobial resistance of H. pylori to metronidazole, clarithromycin and amoxicillin. Materials and Methods: A total of 110 biopsy specimens were collected from patients with clinical symptoms of gastrointestinal disorders who were referred to the endoscopy unit at Al-Zahra Hospital, Isfahan, Iran. We investigated the frequency of H. pylori resistance to metronidazole, clarithromycin and amoxicillin among 48 positive isolates of H. pylori from the referred patients. After the culture of biopsy specimens and identification of H. pylori strains, susceptibility tests were done using the E test (epsilometer test) Results: The overall rates of resistance to metronidazole, clarithromycin and amoxicillin were 56.3%, 14.6% and 4.2% respectively. In our study, there was a significant correlation between resistance to metronidazole and gender (P < 0.05) but there was no significant correlation between resistance to amoxicillin and clarithromycin and gender (P ˃ 0.05). Conclusions: Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. With regards to this study, using metronidazole in the Isfahan region, can lead to eradication failure in clinical therapies due to having the highest rate of resistance but amoxicillin and clarithromycin are prescribed for first and second lines of treatment against H. pylori. Actually, susceptibility testing of H. pylori isolates in different geographical areas is advised because it aids the selection of optimal therapy regimens.

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Section: Introductionmentioning

confidence: 99%

Prevalence of Resistance of Helicobacter pylori Strains to Selected Antibiotics in Isfahan, Iran

Mirzaei

Poursina

Faghri

et al. 2013

Jundishapur J Microbiol

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“…Such resistance clearly decreases the effectiveness of Mtz-containing anti-H. pylori therapies, which tend to be popular because they are relatively inexpensive (Kim et al, 2009).…”

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confidence: 99%

“…If patients infected with Mtz-susceptible H. pylori are treated with the drug, reduction of the nitro moiety of the Mtz produces highly reactive compounds that cause DNA strand breakage, helix destabilization, helix unwinding and, ultimately, death of the bacterial cells (Kwon et al, 2001;Kim et al, 2009). Acquisition of Mtz resistance by H. pylori is highly associated with mutational inactivation of the bacterium's rdxA gene, which encodes an oxygen-insensitive NADPH nitroreductase (Tankovic et al, 2000).…”

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confidence: 99%

Characterisation of the genes encoding resistance to metronidazole (rdxAandfrxA) and clarithromycin (the 23S-rRNA genes) in South African isolates ofHelicobacter pylori

Tanih

Ndip

2011

Annals of Tropical Medicine & Parasitology

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Helicobacter pylori has been incriminated in human diseases, such as peptic ulcer, gastritis and gastric malignancy. Although modern triple-drug regimens are usually highly effective in the treatment of H. pylori infection, the emergence of resistance to two of the most used antibiotics, metronidazole (Mtz) and clarithromycin (Cla), is a serious and increasing problem. Truncations in the rdxA and frxA genes of H. pylori are thought to be associated with Mtz resistance whereas mutations in the pathogen's 23S-ribosomal-RNA (23S-rRNA) genes are associated with Cla resistance. In a recent study, PCR and sequence analysis of the rdxA, frxA and 23S-rRNA genes were used to explore the genetic basis of resistance to Mtz and Cla in H. pylori. When 200 isolates of H. pylori from the Eastern Cape province of South Africa were tested for antibiotic susceptibility, almost all (95.5%) were found resistant to Mtz and 20.0% were found resistant to Cla. Only the Mtz-resistant isolates showed rdxA and frxA truncation. Two point mutations were detected in the 23S-rRNA genes of the Cla-resistant isolates. Many significant changes (resulting in 13 amino-acid substitutions in nine loci and truncated proteins in 14 loci) were observed in the rdxA genes of the Mtz-resistant isolates, and it appears that, compared with the rarer changes detected in frxA, such mutations may contribute more significantly to the high prevalence of Mtz resistance. To guide empiric treatment, the genotypes and antibiotic susceptibility of H. pylori in the Eastern Cape province of South Africa need to be monitored regularly.

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“…Mutations of rdxA , a gene that encodes an oxygen-insensitive NADPH nitroreductase, were the main cause of H. pylori resistance to metronidazole (Goodwin et al, 1998). Additionally, the inactivation of frxA (encoding the NADPH flavin oxidoreductase) and fdxB (encoding the ferredoxin-like protein) may also induce H. pylori resistance to metronidazole (Kim et al, 2009). Recently, Mehrabadi et al assessed the role of the resistance nodulation cell division (RND) family efflux pump in the metronidazole resistance of H. pylori using RT-PCR; they reported that excess amounts of metronidazole increased the gene expression levels of the outer-membrane protein (TolC) homologs of RND pumps (Mehrabadi et al, 2011).…”

Section: Helicobacter Pylori Recurrencementioning

confidence: 99%

Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

Zhu

Lü

2017

Front. Cell. Infect. Microbiol.

130

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Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

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Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA

Cited by 28 publications

References 40 publications

Prevalence of Resistance of Helicobacter pylori Strains to Selected Antibiotics in Isfahan, Iran

Prevalence of Resistance of Helicobacter pylori Strains to Selected Antibiotics in Isfahan, Iran

Characterisation of the genes encoding resistance to metronidazole (rdxAandfrxA) and clarithromycin (the 23S-rRNA genes) in South African isolates ofHelicobacter pylori

Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

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