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Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Helicobacter Pylori | Research article

Genotypic determination of resistance and heteroresistance to clarithromycin in Helicobacter pylori isolates from antrum and corpus of Colombian symptomatic patients

Authors: Betsy Verónica Arévalo-Jaimes, Diana F. Rojas-Rengifo, Carlos Alberto Jaramillo, Belén Mendoza de Molano, José Fernando Vera-Chamorro, María del Pilar Delgado

Published in: BMC Infectious Diseases | Issue 1/2019

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Abstract

Background

The effectiveness of Helicobacter pylori first-line treatment has decreased drastically with the rise of strains resistant to clarithromycin. Therapy failure has also been described in patients with infections by strains with dissimilar antimicrobial susceptibilities. The present study aims to estimate the prevalence of resistance and heteroresistance to clarithromycin in H. pylori isolates from antrum and corpus of Colombian patients.

Methods

The study material included 126 isolates from antrum and corpus biopsies from 63 symptomatic patients over 18 years old who had a gastric endoscopy performed on them between June 2014 to August 2016. PCR amplification and sequencing of the H. pylori 23S rDNA gene was performed to determine the presence of mutations associated with clarithromycin resistance. Random amplified polymorphic DNA analysis was implemented in cases of resistance and heteroresistance.

Results

The overall frequency of resistance to clarithromycin was 38.1% (24/63 patients), of which 19 patients had resistant isolates in both stomach segments (14 with A2143G mutation and 5 with A2142G mutation), and 5 patients had a heteroresistant status. The remaining 61.9% (39/63 patients) presented only susceptible isolates. DNA fingerprinting analysis showed different patterns in 4/22 paired isolates.

Conclusions

The high prevalence of H. pylori clarithromycin-resistance obtained (> 15%) constitutes an alert for gastroenterologists and suggests the need for reconsideration of the current eradication regimen for H. pylori in the studied population. The data show that heteroresistance status is an additional factor to be considered in the assessment of resistance. In consequence, it is advisable to examine at least two biopsies from different gastric segments.
Literature
1.
go back to reference Seia MA, Pereira SV, Fontán CA, De Vito IE, Messina GA, Raba J. Laser-induced fluorescence integrated in a microfluidic immunosensor for quantification of human serum IgG antibodies to helicobacter pylori. Sensors Actuators B Chem. 2012;168(0):297–302.CrossRef Seia MA, Pereira SV, Fontán CA, De Vito IE, Messina GA, Raba J. Laser-induced fluorescence integrated in a microfluidic immunosensor for quantification of human serum IgG antibodies to helicobacter pylori. Sensors Actuators B Chem. 2012;168(0):297–302.CrossRef
2.
go back to reference IARC. Schistosomes, liver flukes and helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1–241. IARC. Schistosomes, liver flukes and helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1–241.
3.
go back to reference Kao C-Y, Lee A-Y, Huang A-H, Song P-Y, Yang Y-J, Sheu S-M, Chang W-L, Sheu B-S, Wu J-J. Heteroresistance of helicobacter pylori from the same patient prior to antibiotic treatment. Infect Genet Evol. 2014;23:196–202.CrossRef Kao C-Y, Lee A-Y, Huang A-H, Song P-Y, Yang Y-J, Sheu S-M, Chang W-L, Sheu B-S, Wu J-J. Heteroresistance of helicobacter pylori from the same patient prior to antibiotic treatment. Infect Genet Evol. 2014;23:196–202.CrossRef
4.
go back to reference Noguchi N, Rimbara E, Kato A, Tanaka A, Tokunaga K, Kawai T, Takahashi S, apos, ichi, Sasatsu M. Detection of mixed clarithromycin-resistant and -susceptible helicobacter pylori using nested PCR and direct sequencing of DNA extracted from faeces. J Med Microbiol 2007, 56(9):1174–1180.CrossRef Noguchi N, Rimbara E, Kato A, Tanaka A, Tokunaga K, Kawai T, Takahashi S, apos, ichi, Sasatsu M. Detection of mixed clarithromycin-resistant and -susceptible helicobacter pylori using nested PCR and direct sequencing of DNA extracted from faeces. J Med Microbiol 2007, 56(9):1174–1180.CrossRef
5.
go back to reference Taylor DE, Ge Z, Purych D, Lo T, Hiratsuka K. Cloning and sequence analysis of two copies of a 23S rRNA gene from helicobacter pylori and association of clarithromycin resistance with 23S rRNA mutations. Antimicrob Agents Chemother. 1997;41(12):2621–8.CrossRef Taylor DE, Ge Z, Purych D, Lo T, Hiratsuka K. Cloning and sequence analysis of two copies of a 23S rRNA gene from helicobacter pylori and association of clarithromycin resistance with 23S rRNA mutations. Antimicrob Agents Chemother. 1997;41(12):2621–8.CrossRef
6.
go back to reference Selgrad M, Tammer I, Langner C, Bornschein J, Meißle J, Kandulski A, Varbanova M, Wex T, Schlüter D, Malfertheiner P. Different antibiotic susceptibility between antrum and corpus of the stomach, a possible reason for treatment failure of helicobacter pylori infection. World J Gastroenterol: WJG. 2014;20(43):16245.CrossRef Selgrad M, Tammer I, Langner C, Bornschein J, Meißle J, Kandulski A, Varbanova M, Wex T, Schlüter D, Malfertheiner P. Different antibiotic susceptibility between antrum and corpus of the stomach, a possible reason for treatment failure of helicobacter pylori infection. World J Gastroenterol: WJG. 2014;20(43):16245.CrossRef
7.
go back to reference Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, Jones NL, Render C, Leontiadis GI, Moayyedi P. The Toronto consensus for the treatment of helicobacter pylori infection in adults. Gastroenterology. 2016;151(1):51–69 e14.CrossRef Fallone CA, Chiba N, van Zanten SV, Fischbach L, Gisbert JP, Hunt RH, Jones NL, Render C, Leontiadis GI, Moayyedi P. The Toronto consensus for the treatment of helicobacter pylori infection in adults. Gastroenterology. 2016;151(1):51–69 e14.CrossRef
8.
go back to reference Acosta CP, Hurtado FA, Trespalacios AA. Determinación de mutaciones de un solo nucleótido en el gen 23S rRNA de Helicobacter pylori relacionadas con resistencia a claritromicina en una población del departamento del Cauca, ColombiaJF - Biomédica. Biomédica. 2014;34:156–62.CrossRef Acosta CP, Hurtado FA, Trespalacios AA. Determinación de mutaciones de un solo nucleótido en el gen 23S rRNA de Helicobacter pylori relacionadas con resistencia a claritromicina en una población del departamento del Cauca, ColombiaJF - Biomédica. Biomédica. 2014;34:156–62.CrossRef
9.
go back to reference Trespalacios AA, Otero W, Caminos JE, Mercado MM, Ávila J, Rosero LE, Arévalo A, Poutou-Piñales RA, Graham DY. Phenotypic and genotypic analysis of clarithromycin-resistant helicobacter pylori from Bogotá D.C., Colombia. J Microbiol. 2013;51(4):448–52.CrossRef Trespalacios AA, Otero W, Caminos JE, Mercado MM, Ávila J, Rosero LE, Arévalo A, Poutou-Piñales RA, Graham DY. Phenotypic and genotypic analysis of clarithromycin-resistant helicobacter pylori from Bogotá D.C., Colombia. J Microbiol. 2013;51(4):448–52.CrossRef
10.
go back to reference Rimbara E, Sasatsu M, Graham DY. PCR detection of helicobacter pylori in clinical samples. Methods in molecular biology (Clifton, NJ). 2013;943:279–87.CrossRef Rimbara E, Sasatsu M, Graham DY. PCR detection of helicobacter pylori in clinical samples. Methods in molecular biology (Clifton, NJ). 2013;943:279–87.CrossRef
11.
go back to reference Jiménez-Soto LF, Rohrer S, Jain U, Ertl C, Sewald X, Haas R. Effects of cholesterol on helicobacter pylori growth and virulence properties in vitro. Helicobacter. 2012;17(2):133–9.CrossRef Jiménez-Soto LF, Rohrer S, Jain U, Ertl C, Sewald X, Haas R. Effects of cholesterol on helicobacter pylori growth and virulence properties in vitro. Helicobacter. 2012;17(2):133–9.CrossRef
12.
go back to reference Álvarez A, Moncayo JI, Santacruz JJ, Corredor LF, Reinosa E, Martínez JW, Beltrán L. Resistencia a metronidazol y claritromicina en aislamientos de Helicobacter pylori de pacientes dispépticos en Colombia. Rev Med Chil. 2009;137:1309–14.PubMed Álvarez A, Moncayo JI, Santacruz JJ, Corredor LF, Reinosa E, Martínez JW, Beltrán L. Resistencia a metronidazol y claritromicina en aislamientos de Helicobacter pylori de pacientes dispépticos en Colombia. Rev Med Chil. 2009;137:1309–14.PubMed
13.
go back to reference Akopyanz N, Bukanov NO, Westblom TU, Kresovich S, Berg DE. DNA diversity among clinical isolates of helicobacter pylori detected by PCR-based RAPD fingerprinting. Nucleic Acids Res. 1992;20(19):5137–42.CrossRef Akopyanz N, Bukanov NO, Westblom TU, Kresovich S, Berg DE. DNA diversity among clinical isolates of helicobacter pylori detected by PCR-based RAPD fingerprinting. Nucleic Acids Res. 1992;20(19):5137–42.CrossRef
15.
go back to reference McHugh ML. Interrater reliability: the kappa statistic. Biochemia Medica. 2012;22(3):276–82.CrossRef McHugh ML. Interrater reliability: the kappa statistic. Biochemia Medica. 2012;22(3):276–82.CrossRef
16.
go back to reference Trespalacios AA, Rimbara E, Otero W, Reddy R, Graham DY. Improved allele-specific PCR assays for detection of clarithromycin and fluoroquinolone resistant of helicobacter pylori in gastric biopsies: identification of N87I mutation in GyrA. Diagn Microbiol Infect Dis. 2015;81(4):251–5.CrossRef Trespalacios AA, Rimbara E, Otero W, Reddy R, Graham DY. Improved allele-specific PCR assays for detection of clarithromycin and fluoroquinolone resistant of helicobacter pylori in gastric biopsies: identification of N87I mutation in GyrA. Diagn Microbiol Infect Dis. 2015;81(4):251–5.CrossRef
17.
go back to reference Park JY, Dunbar KB, Mitui M, Arnold CA, Lam-Himlin DM, Valasek MA, Thung I, Okwara C, Coss E, Cryer B, et al. Helicobacter pylori clarithromycin resistance and treatment failure are common in the USA. Dig Dis Sci. 2016;61(8):1–8.CrossRef Park JY, Dunbar KB, Mitui M, Arnold CA, Lam-Himlin DM, Valasek MA, Thung I, Okwara C, Coss E, Cryer B, et al. Helicobacter pylori clarithromycin resistance and treatment failure are common in the USA. Dig Dis Sci. 2016;61(8):1–8.CrossRef
18.
go back to reference Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M, Hirschl AM, Andersen LP, Goossens H, Glupczynski Y. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 2012;62(1):34.CrossRef Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M, Hirschl AM, Andersen LP, Goossens H, Glupczynski Y. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 2012;62(1):34.CrossRef
19.
go back to reference Sarem M, Corti R. Role of helicobacter pylori coccoid forms in infection and recrudescence. Gastroenterología y Hepatología (English Edition). 2016;39(1):28–35.CrossRef Sarem M, Corti R. Role of helicobacter pylori coccoid forms in infection and recrudescence. Gastroenterología y Hepatología (English Edition). 2016;39(1):28–35.CrossRef
20.
go back to reference Álvarez A, Moncayo JI, Santacruz JJ, Santacoloma M, Corredor LF, Reinosa E. Antimicrobial susceptibility and mutations involved in clarithromycin resistance in helicobacter pylori isolates from patients in the Western central region of Colombia. Antimicrob Agents Chemother. 2009;53(9):4022–4.CrossRef Álvarez A, Moncayo JI, Santacruz JJ, Santacoloma M, Corredor LF, Reinosa E. Antimicrobial susceptibility and mutations involved in clarithromycin resistance in helicobacter pylori isolates from patients in the Western central region of Colombia. Antimicrob Agents Chemother. 2009;53(9):4022–4.CrossRef
21.
go back to reference Trespalacios Rangel AA. Estudio de la resistencia de Helicobacter pylori a los antimicrobianos e implicaciones en las terapias de erradicación. Bogotá: Pontificia Universidad Javeriana; 2011. Trespalacios Rangel AA. Estudio de la resistencia de Helicobacter pylori a los antimicrobianos e implicaciones en las terapias de erradicación. Bogotá: Pontificia Universidad Javeriana; 2011.
22.
go back to reference Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY. Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6–30.CrossRef Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY. Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6–30.CrossRef
23.
go back to reference Otero RW, Trespalacios RAA, Otero PL, Vallejo OMT, Torres Amaya M, Pardo R, Sabbagh L. Guía de práctica clínica para el diagnóstico y tratamiento de la infección por Helicobacter pylori en adultos. Revista Colombiana de Gastroenterologia. 2015;30:17–33. Otero RW, Trespalacios RAA, Otero PL, Vallejo OMT, Torres Amaya M, Pardo R, Sabbagh L. Guía de práctica clínica para el diagnóstico y tratamiento de la infección por Helicobacter pylori en adultos. Revista Colombiana de Gastroenterologia. 2015;30:17–33.
24.
go back to reference Wang G, Wilson TJM, Jiang Q, Taylor DE. Spontaneous mutations that confer antibiotic resistance inHelicobacter pylori. Antimicrob Agents Chemother. 2001;45(3):727–33.CrossRef Wang G, Wilson TJM, Jiang Q, Taylor DE. Spontaneous mutations that confer antibiotic resistance inHelicobacter pylori. Antimicrob Agents Chemother. 2001;45(3):727–33.CrossRef
25.
go back to reference Gong Y, Yuan Y. Resistance mechanisms of helicobacter pylori and its dual target precise therapy. Crit Rev Microbiol. 2018:1–22. Gong Y, Yuan Y. Resistance mechanisms of helicobacter pylori and its dual target precise therapy. Crit Rev Microbiol. 2018:1–22.
Metadata
Title
Genotypic determination of resistance and heteroresistance to clarithromycin in Helicobacter pylori isolates from antrum and corpus of Colombian symptomatic patients
Authors
Betsy Verónica Arévalo-Jaimes
Diana F. Rojas-Rengifo
Carlos Alberto Jaramillo
Belén Mendoza de Molano
José Fernando Vera-Chamorro
María del Pilar Delgado
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2019
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-019-4178-x

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