Refractoriness to anti-Helicobacter pylori treatment attributed to phenotypic resistance patterns in patients with gastroduodenopathy in Guayaquil-Ecuador
Javier David Lara Icaza
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Universidad del Zulia (LUZ), Maracaibo, Venezuela
Search for more papers by this authorRosalina Lara Tapia
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Search for more papers by this authorCorresponding Author
Cástula Tania Castro Triana
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador
Correspondence
Cástula Tania Castro Triana, Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador; Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador.
Email: castula.triana@cu.ucsg.edu.ec
Search for more papers by this authorLaura Catalina Romero Ramírez
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Search for more papers by this authorJavier David Lara Icaza
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Universidad del Zulia (LUZ), Maracaibo, Venezuela
Search for more papers by this authorRosalina Lara Tapia
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Search for more papers by this authorCorresponding Author
Cástula Tania Castro Triana
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador
Correspondence
Cástula Tania Castro Triana, Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador; Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador.
Email: castula.triana@cu.ucsg.edu.ec
Search for more papers by this authorLaura Catalina Romero Ramírez
Centro Clínico Quirúrgico Ambulatorio (Hospital del Día) Efrén Jurado López, Guayaquil, Ecuador
Search for more papers by this authorAbstract
Background
Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador.
Methods
A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied.
Results
All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin–amoxicillin was 43.4%, to tetracycline–metronidazole 30.3%, to amoxicillin–levofloxacin 27.6%, and to clarithromycin–metronidazole 59.2%.
Conclusions
In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.
Open Research
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are available in the supplementary material of this article.
Supporting Information
| Filename | Description |
|---|---|
| hel13060-sup-0001-AppendixS1.docxWord 2007 document , 17.3 MB |
Appendix S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Lopo I, Libânio D, Pissta I, Dinis-Ribeiro M, Pimentel-Nunes P. Helicobacter pylori antibiotic resistance in Portugal: systematic review and meta-analysis. Helicobacter. 2018; 23:e12493. doi:10.1111/hel.12493
- 2Shah SC, Iyer PG, Moss SF. AGA clinical practice update on the Management of Refractory Helicobacter pylori infection: expert review. Gastroenterology. 2021; 160: 1831-1841. doi:10.1053/j.gastro.2020.11.059
- 3Santos ML, de Brito BB, da Silva FA, et al. Helicobacter pylori infection: beyond gastric manifestations. World J Gastroenterol. 2020; 26: 4076-4093. doi:10.3748/wjg.v26.i28.4076
- 4Roque F. "Helicobacter pylori, hoy" a 30 años de historia. Rev Med Clin Condes. 2015; 26: 575-578. doi:10.1016/j.rmclc.2015.09.004
10.1016/j.rmclc.2015.09.004 Google Scholar
- 5Lara JD, Cruz CP. Prevalencia de Helicobacter pylori por antígeno fecal en pacientes sintomáticos del Centro Ambulatorio de Guayaquil-Ecuador. Recimundo. 2019; 3: 78-92. doi:10.26820/recimundo/3
10.26820/recimundo/3.(4).diciembre.2019.78-92 Google Scholar
- 6Cosme A, Torrente S, Montes M, et al. Helicobacter pylori antimicrobial resistance during a 5-year period (2013-2017) in northern Spain and its relationship with the eradication therapies. Helicobacter. 2018; 24:e12557. doi:10.1111/hel.12557
- 7Yuan C, Jun P, Xi J, et al. Repetitive position change improves gastric cleanliness for magnetically controlled capsule gastrocopy. Dig Dis Sci. 2019; 64: 1297-1304. doi:10.1007/s10620-018-5415-7
- 8Hirata Y, Yamada A, Niikura R, Shichijo S, Hayakawa Y, Koike K. Efficacy and safety of a new rifabutin-based triple therapy with vonoprazan for refractory Helicobacter pylori infection: a prospective single-arm study. Helicobacter. 2020; 25(5):e12719. doi:10.1111/hel.12719
- 9Lin TF, Hsu PI. Second-line rescue treatment of Helicobacter pylori infection: where are we now? World J Gastroenterol. 2018; 24: 4548-4553. doi:10.3748/wjg.v24.i40.4548
- 10Roszczenko P, Ilona M, Jagusztyn E. Helicobacter pylori treatment in the post-antibiotic's era-searching for new drug targets. Appl Microbiol Biotechnol. 2020; 104: 9891-9905. doi:10.1007/s00253-020-10945-w
- 11Reyes JA, Guzmán KV, Pacheco RE, et al. Susceptibilidad antibiótica de Helicobacter pylori: estudio de prevalencia en pacientes con dispepsia en Quito-Ecuador. Rev Colomb Gastroenterol. 2017; 32(4): 305-310. doi:10.22516/25007440.173
10.22516/25007440.173 Google Scholar
- 12Risina E, Donday M, Samuel M, et al. Evaluation of a new monoclonal chemiluminescent immunoassy stool antigen test for the diagnosis of Helicobacter pylori infection: a Spanish multicentre study. J Clin Med. 2022; 11: 115077. doi:10.3390/jcm11175077
- 13Alzoubi H, Al-Mnayyis A, Al Rfoa I, et al. The use of 13C-urea breath test for non-invasive diagnosis of helicobacter pylori infection in comparison to endoscopy and stool antigen test. Diagnostics (Basel). 2020; 10(7): 448. doi:10.3390/diagnostics10070448
- 14Vargas G, Balvin Yanes L, Chaiña Meza JM, Llanos Tejada F. Adherencia terapéutica al tratamiento de erradicación de Helicobacter pylori y sus factores asociados en un hospital público de Perú. Rev Gastroenterol Peru. 2020; 40(3): 224-229.
- 15 European Committee on Antimicrobial Susceptibility Testing (ECTS). Breakpoint tables for interpretation of MICs and zone diameters. EUCAST clinical breakpoint table v.5.0, válida desde 2015-01-01.
- 16Velasco B, Duran C, Bahamondez Cañas T. New perspective in the treatment of Helicobacter pylori infection. Ars Med. 2021; 46(3): 60-69. doi:10.11565/arsmed.v46i3.1803
10.11565/arsmed.v46i3.1803 Google Scholar
- 17Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut. 2017; 66(1): 6-30. doi:10.1136/gutjnl-2016-312288
- 18Paz S, Florez Bracho L, Lasa JS, Zubiaurre I. Helicobacter pylori infection. Frequency of first-line treatment failure. Medicina (B Aires). 2020; 80(2): 111-116.
- 19Menéndez-Morales D et al. Erradicación de Helicobacter pylori con triple terapia estándar de primera línea. Ciencia, tecnología y Salud. 2018; 5(1): 54-62. doi:10.36829/63CTS.v5i1.381
10.36829/63CTS.v5i1.381 Google Scholar
- 20Ladrón de Guevara L, Bornstein-Quevedo L, González-Huezo S, Castañeda-Romero B, Costa FG, di Silvio-López M. Erradicación de Helicobacter pylori en México con un régimen basado en levofloxacino versus terapia triple estándar: resultados de un ensayo clínico de fase IIIb, abierto, aleatorizado y de no inferioridad. Rev Gastroenterol Mex. 2019; 84(3): 274-283. doi:10.1016/j.rgmx.2018.04.005
- 21Arenas A, Serrano C, Quiñones L, et al. Alta prevalencia de resistencia a claritromicina y efecto sobre la erradicación de Helicobacter pylori en una población de Santiago de Chile: estudio de cohortes y metaanálisis. Sci Rep. 2019; 9(1): 20070. doi:10.1038/s41598-019-56399-7
- 22Marval F et al. Terapia convencional y secuencial en el tratamiento de Helicobacter pylori en pacientes del estado Carabobo, Venezuela. Correo Científico Médico. 2016; 20(4): 729-740.
- 23Shakya SS, Bhandari M, Thapa SR, et al. Medication adherence pattern and factors affecting adherence in Helicobacter pylori eradication therapy. Kathmandu Univ Med J KUMJ. 2016; 14(53): 58-64.
- 24Zurita J, Sevillano G, Paz Y Miño A, et al. Mutations associated with Helicobacter pylori antimicrobial resistance in the Ecuadorian population. J Appl Microbiol. 2021; 132(4): 1-11. doi:10.1111/jam.15396
- 25Best L, Takwoingi Y, Siddique S, et al. Non-invasive diagnostic test for Helicobacter pylori infection. Cochrane Database Syst Rev. 2018; 3(3): 1-24. doi:10.1002/14651858.CD012080.pub2
10.1002/14651858.CD012080.pub2 Google Scholar
- 26Bosques Padilla FJ, Remes-Troche JM, González-Huezo MS, et al. Cuarto consenso mexicano sobre Helicobacter pylori. Rev Gastroenterol Mex (Engled). 2018; 83(3): 325-341. doi:10.1016/j.rgmx.2018.05.003
- 27Liou JM, Chen PY, Kuo YT, Wu MS. Toward population specific and personalized treatment of Helicobacter pylori infection. J Biomed Sci. 2018; 25(1): 70. doi:10.1186/s12929-018-0471-z
- 28Guzmán J, Castillo D, Ojeda M, Sauvain M. Antimicrobial susceptibility and mutations in the 23S rRNA gen of Helicobacter pylori in dyspeptic patients. Rev Perú Med Exp Salud Pública. 2019; 36: 270-274. doi:10.17843/rpmesp.2019.362.3901
- 29Otero RW, Gómez ZM, Otero PL, Trespalacios RA. Helicobacter pylori: ¿cómo se trata en 2018? Rev Gastroenterol Peru. 2018; 38(1): 54-69.
- 30Queiroz DM, Saito M, Rocha GA, et al. Helicobacter pylori infection in infants and toddlers in South America: concordance between [13C] urea breath test and monoclonal H. Pylori stool antigent test. J Clin Microbiol. 2013; 51(11): 3735-3740. doi:10.1128/JCM.01752-13
- 31Toyoshima O, Nishizawa T, Koike K. Endoscopic Kyoto classification of helicobacter pylori infection and gastric cancer risk diagnosis. World J Gastroenterol. 2020; 26(5): 466-477. doi:10.3748/wjg.v26.i5.466
- 32Bang CS, Lee JJ, Baik GH. Artificial intelligence for the prediction of Helicobacter pylori infection in endoscopic images: systematic review and meta-analysis of diagnostic test accuracy. J Med Internet Res. 2020; 22(9):e21983. doi:10.2196/21983
- 33Levine M. Úlceras pépticas. In: M Gore Richard, S Levine Marc, eds. Textbook of Gastrointestinal Radiology. Third ed. Saunders; 2008 ISBN-13:978–1416023326. ISBN-10:1416023321.
- 34Malfertheiner P, Selgrad M. Helicobacter pylori infection and current clinical areas of contention. Curr Opin Gastroenterol. 2010; 26(6): 618-623. doi:10.1097/MOG.0b013e32833efede
- 35Escobedo-Belloc M, Bosques-Padilla F. The rise of Helicobacter pylori resistance to antibiotics in Mexico: is azithromycin plus levofloxacin the answer? Rev Gastroenterol Mex (Engl Ed). 2019; 84(3): 271-273. doi:10.1016/j.rgmx.2018.10.005
- 36Trespalacios AA, Otero W, Arévalo-Galvis A, Poutou-Piñales RA, Rimbara E, Graham DY. Vigilancia de la resistencia a levofloxacino en aislamientos de Helicobacter pylori en Bogotá-Colombia (2009-2014). PLoS One. 2016; 11(7):e0160007. doi:10.1371/journal.pone.0160007
- 37Greenberg ER, Anderson GL, Morgan DR, et al. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomized trial. Lancet. 2011; 378(9790): 507-514. doi:10.1016/S0140-6736(11)60825-8
- 38Debets-Ossenkopp YJ, Reyes G, Mulder J, et al. Characteristics of clinical Helicobacter pylori strains from Ecuador. J Antimicrob Chemother. 2003; 51(1): 141-145. doi:10.1093/jac/dkg023
- 39Oporto M, Pavez M, Troncoso C, et al. Prevalence of infection and antibiotic susceptibility of Helicobacter pylori: an evaluation in public and private health Systems of Southern Chile. Pathogens. 2019; 8(4): 226. doi:10.3390/pathogens8040226
- 40Atehortúa JD et al. Descripción de la resistencia de Helicobacter Pylori a seis antibióticos de uso frecuente en Colombia. Rev Colomb Gastroenterol. 2020; 35(3): 351-361. doi:10.22516/25007440.493
10.22516/25007440.493 Google Scholar
- 41Cavazza ME et al. Susceptibilidad antibiótica en cepas de Helicobacter pylori aisladas de pacientes venezolanos con úlcera duodenal. Rev de la Sociedad Venezolana de Microbiologia. 2017; 37: 75-77.
- 42Zerbetto De Palma G, Mendiondo N, Wonaga A, et al. Occurrence of mutation in the antimicrobial target genes related to levofloxacin, clarithromycin, and amoxicillin resistance in Helicobacter pylori isolates from Buenos Aires city. Microb Drug Resist. 2017; 23(3): 351-358. doi:10.1089/mdr.2015.0361
- 43Olano M, Chu M, Guzmán J, Castillo D, Sauvain M. Rendimiento diagnóstico del cultivo y susceptibilidad de Helicobacter pylori en pacientes peruanos: resultados de un laboratorio centinela. Rev Peru Med Exp Salud Publica. 2021; 38: 406-411. doi:10.17843/rpmesp.2021.383.7256
- 44Boehnke KF, Valdivieso M, Bussalleu A, et al. Antibiotic resistance among Helicobacter pylori clinical isolates in Lima. Peru Infect Drug Resist. 2017; 10: 85-90. doi:10.2147/IDR.S123798
- 45Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO prority listo of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018; 18(3): 318-327. doi:10.1016/S1473-3099(17)30753-3
- 46Gisbert JP, McNicholl AG. Optimization strategies aimed to increase the efficacy of Helicobacter pylori eradication therapies. Helicobacter. 2017; 22(4):e12392. doi:10.1111/hel.12392
- 47Wang D, Guo Q, Yuan Y, Gong Y. The antibiotic resistance of Helicobacter pylori to five antibiotics and influencing factors in an area of China with a high risk of gastric cancer. BMC Microbiol. 2019; 19: 152. doi:10.1186/s12866-019-1517-4
- 48Jia-Li H, Yang J, Zhou YB, et al. Optimized high-dose amoxicillin-proton-pump inhibitor dual therapies fail to achieve high cure rates in China. Saudi. J Gastroenterol. 2017; 23(5): 275-280. doi:10.4103/sjg.SJG_91_17
- 49Garrido-Treviño VAF, López-Martínez M, Flores-Hinojosa JA, Tijerina-Rodríguez L, Bosques-Padilla F. Empiric treatment VS susceptibility-guieded treatment for eradicating Helicobacter pylori: is it possible to change that paradigm using modern molecular methods? Revista de Gastroenterologia de México. 2022; 87(3): 330-341. doi:10.1016/j.rgmxen.2022.06.003
- 50Buitrago-Laguado J, Ruiz Linares C, Otero Regino WA. The efficacy of dual therapy for eradicating H. Pylori in a Colombian population. Acta médica Colombiana. 2021; 46(4): 1-11. doi:10.36104/amc.2021.2091
10.36104/amc.2021.2091 Google Scholar
- 51Villalón F et al. Tratamiento y manejo de la infección por Helicobacter pylori. Gastroenterollatinoam. 2020; 31(3): 136-346.
- 52Arévalo GA, Trespalacios Rangel AA, Otero Regino W. Personalized therapy for helicobacter pylori: CYP2C19 genotype effect on first-line triple therapy. Helicobacter. 2019; 24(3):e12574. doi:10.1111/hel.12574
- 53Lee H, Kim BJ, Kim SG, et al. Concomitant, sequential, and 7-day triple therapy in first-line treatment of helicobacter pylori infection in Korea: study protocol for a randomized controlled trial. Bio Med Central. 2017; 18: 549. doi:10.1186/s13063-017-2281-0
10.1186/s13063-017-2281-0 Google Scholar
- 54Abadi A, Yamaoka Y. Helicobacter pylori therapy and clinical perspective. Journal of Global Antimicrobial Resistance. 2018; 14: 117. doi:10.1016/j.jgar.2018.03.005
- 55Win TM, Htun M, Myint WPP, Aung MM, Ni N. High-dose dual therapy and CYP2C19 polymorphism in Helicobacter pylori eradication. Gastroenterol Hepatol. 2021; 3(3): 379-383. doi:10.1002/ygh2.484
10.1002/ygh2.484 Google Scholar
- 56Zabala Torres B, Lucero Y, Lagomarcino AJ, et al. Prevalence and dynamics of Helicobacter pylori infection during childhood. Helicobacter. 2017; 22(5): 1-14. doi:10.1111/hel.12399
