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      Surveillance of Levofloxacin Resistance in Helicobacter pylori Isolates in Bogotá-Colombia (2009-2014)

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          Abstract

          Increased resistance of Helicobacter pylori to clarithromycin and metronidazole has resulted in recommendation to substitute fluoroquinolones for eradication therapy. The aims of the study were to determine the prevalence and changes in primary levofloxacin resistance related to H. pylori gyrA sequences. The study utilized H. pylori strains isolated from patients undergoing gastroscopy in Bogotá, Colombia from 2009 to 2014. Levofloxacin susceptibility was assessed by agar dilution. Mutations in gyrA sequences affecting the quinolone resistance-determining region (QRDR) were evaluated by direct sequencing. Overall, the mean prevalence of primary levofloxacin resistance was 18.2% (80 of 439 samples). Resistance increased from 11.8% (12/102) in 2009 to 27.3% (21/77) in 2014 (p = 0.001). gyrA mutations in levofloxacin resistant strains were present in QRDR positions 87 and 91. The most common mutation was N87I (43.8%, 35/80) followed by D91N (28.8%, 23/80) and N87K (11.3%, 9/80). Levofloxacin resistance increased markedly in Colombia during the six-year study period. Primary levofloxacin resistance was most often mediated by point mutations in gyrA, with N87I being the most common QRDR mutation related to levofloxacin resistance.

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          Helicobacter pylori treatment in the era of increasing antibiotic resistance.

          David Graham, Lori Fischbach (2010)
          With few exceptions, the most commonly recommended triple Helicobacter pylori regimen (proton pump inhibitor (PPI), amoxicillin and clarithromycin) now provides unacceptably low treatment success. A review of worldwide results suggests that successful eradication using a triple regimen is not consistently observed in any population. Clinicians should use 'only use what works locally' and ignore consensus statements and society guidelines if they are not consistent with local results. Clinical trials should be result based, with the goal of identifying regimens with >90-95% success. New treatments should be only be compared with the currently locally effective treatment (>90%) or a historical untreated control (which has been shown to reliably yield 0% eradication); trials using placebos or treatments known to be inferior are with rare exceptions unethical. If a highly effective regimen is not available locally, we recommend trying a 14 day concomitant quadruple treatment regimen containing a PPI, amoxicillin, clarithromycin and a nitroimidazole; 10 day sequential treatment (PPI plus amoxicillin for 5 days followed by a PPI, clarithromycin and a nitroimidazole for 5 days); or 14 day bismuth-containing quadruple treatments. Treatments needing further evaluation include those containing furazolidone or nitazoxanide, hybrids of sequential-concomitant therapies and amoxicillin-PPI dual therapy with PPI doses such that they maintain intragastric pH >6.
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            American College of Gastroenterology guideline on the management of Helicobacter pylori infection.

            William Chey, Benjamin C Y Wong (2007)
            Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H. pylori remains an important factor linked to the development of peptic ulcer disease, gastric malignanc and dyspeptic symptoms. Whether to test for H. pylori in patients with functional dyspepsia, gastroesophageal reflux disease (GERD), patients taking nonsteroidal antiinflammatory drugs, with iron deficiency anemia, or who are at greater risk of developing gastric cancer remains controversial. H. pylori can be diagnosed by endoscopic or nonendoscopic methods. A variety of factors including the need for endoscopy, pretest probability of infection, local availability, and an understanding of the performance characteristics and cost of the individual tests influences choice of evaluation in a given patient. Testing to prove eradication should be performed in patients who receive treatment of H. pylori for peptic ulcer disease, individuals with persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-associated MALT lymphoma, and individuals who have undergone resection of early gastric cancer. Recent studies suggest that eradication rates achieved by first-line treatment with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin have decreased to 70-85%, in part due to increasing clarithromycin resistance. Eradication rates may also be lower with 7 versus 14-day regimens. Bismuth-containing quadruple regimens for 7-14 days are another first-line treatment option. Sequential therapy for 10 days has shown promise in Europe but requires validation in North America. The most commonly used salvage regimen in patients with persistent H. pylori is bismuth quadruple therapy. Recent data suggest that a PPI, levofloxacin, and amoxicillin for 10 days is more effective and better tolerated than bismuth quadruple therapy for persistent H. pylori infection, though this needs to be validated in the United States.
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              Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection.

              Carolyn S. P. Lam, Tiing Ang, Khean-Lee Goh … (2009)
              The Asia-Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long-established indications, such as peptic ulcer disease, early mucosa-associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long-term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population 'test and treat' strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long-term aspirin or non-steroidal anti-inflammatory drug therapy in patients at high risk for ulcers and ulcer-related complications. In Asia, the currently recommended first-line therapy for H. pylori infection is PPI-based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth-based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI-based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first-line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth-based quadruple therapy; (iii) levofloxacin-based triple therapy; and (iv) rifabutin-based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.
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                Author and article information

                Contributors
                Massimiliano Galdiero: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 25 July 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 7
                Electronic Location Identifier: e0160007
                Affiliations
                [1 ]Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia
                [2 ]Unidad de Gastroenterología, Universidad Nacional de Colombia, Bogotá, D.C, Colombia
                [3 ]Grupo de Biotecnología Ambiental e Industrial (GBAI). Departamento de Microbiología, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia
                [4 ]Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston TX, United States of America
                [5 ]Baylor College of Medicine, Houston TX, United States of America
                Second University of Naples, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AAT-R WO DYG. Performed the experiments: AA-G AAT-R. Analyzed the data: AAT-R AA-G WO AA-G RAP-P ER DYG. Wrote the paper: AAT-R WO AA-G RAP-P ER DYG.

                Article
                Publisher ID: PONE-D-16-06492
                DOI: 10.1371/journal.pone.0160007
                PMC ID: 4959775
                PubMed ID: 27454429
                SO-VID: 176b8c01-5556-4d5f-9b71-b0887253517d
                License:

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                Date received : 15 February 2016
                Date accepted : 12 July 2016
                Page count
                Figures: 2, Tables: 1, Pages: 10
                Funding
                Funded by: COLCIENCIAS
                Award ID: 120340820464
                Award Recipient : Alba A. Trespalacios-Rángel
                Funded by: Pontificia Universidad Javeriana
                Award ID: 00004554
                Award Recipient : Alba A. Trespalacios-Rángel
                Funded by: Office of Research and Development Medical Research Service Department of Veterans Affairs
                Award ID: DK56338
                Award Recipient :
                Funded by: Texas Medical Center Digestive Diseases Center
                Award ID: DK067366
                Award Recipient :
                This work was supported by COLCIENCIAS (Colombia), Grant 120340820464, Pontificia Universidad Javeriana, Bogotá, D.C. (Colombia) Grant 00004554 and by Michael E. DeBakey Veterans Affairs Medical Center Internal Project and the Baylor College of Medicine, United States. Dr. Graham was supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service Grant DK56338, which funds the Texas Medical Center Digestive Diseases Center and DK067366.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Bacterial Pathogens
                Subject: Helicobacter Pylori
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Bacterial Pathogens
                Subject: Helicobacter Pylori
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Bacteria
                Subject: Helicobacter
                Subject: Helicobacter Pylori
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Mutation
                Subject: Point Mutation
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Mutation
                Subject: Substitution Mutation
                Subject: Biology and Life Sciences
                Subject: Molecular Biology
                Subject: Molecular Biology Techniques
                Subject: Artificial Gene Amplification and Extension
                Subject: Polymerase Chain Reaction
                Subject: Research and Analysis Methods
                Subject: Molecular Biology Techniques
                Subject: Artificial Gene Amplification and Extension
                Subject: Polymerase Chain Reaction
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: DNA
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Nucleic Acids
                Subject: DNA
                Subject: People and places
                Subject: Geographical locations
                Subject: South America
                Subject: Colombia
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancer Treatment
                Subject: Medicine and Health Sciences
                Subject: Pharmacology
                Subject: Drugs
                Subject: Antimicrobials
                Subject: Antibiotics
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Microbial Control
                Subject: Antimicrobials
                Subject: Antibiotics
                Custom metadata
                Data Availability Data are available from Figshare: https://figshare.com/s/c1928ecda291ed2c61fa doi: 10.6084/m9.figshare.3386065.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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