Helicobacter pylori: resistencia múltiple en pacientes de Bogotá, Colombia

Azucena Arévalo, William Alberto Otero, Alba Alicia Trespalacios, .

Palabras clave: Helicobacter pylori, resistencia a múltiples medicamentos, antibacterianos, mutación, terapia

Resumen

Introducción. La resistencia a los antibióticos es la principal causa del fracaso del tratamiento contra Helicobacter pylori; la claritromicina y el metronidazol son los antibióticos que generan mayor resistencia. En Colombia, la resistencia primaria a estos dos antibióticos y el uso excesivo de levofloxacina han alcanzado los límites aceptados (13,6, 83 y 16 %, respectivamente). A pesar de ello, se usa el tratamiento empírico combinando estos antibióticos en pacientes en los que ha fallado anteriormente.
Objetivo. Determinar la resistencia a los antibióticos en pacientes previamente tratados para H. pylori en Bogotá, Colombia.
Materiales y métodos. Se llevó a cabo un estudio descriptivo en el que se evaluó mediante dilución en agar la resistencia a la amoxicilina, la claritromicina, la levofloxacina y el metronidazol en 10 aislamientos provenientes de 5 pacientes con tres o cuatro tratamientos fallidos para H. pylori. La resistencia a los antibióticos se confirmó mediante secuenciación de ADN (Magrogen, Korea).
Resultados. Ocho de los aislamientos presentaron resistencia a dos o más antibióticos y todos fueron resistentes a la levofloxacina. Los patrones de sensibilidad de los aislamientos provenientes del antro pilórico y del cuerpo del estómago, fueron diferentes en tres de los pacientes.
Conclusión. Hasta donde se sabe, esta es la primera evidencia de resistencia múltiple de H. pylori en Colombia en pacientes previamente tratados. Los resultados evidenciaron las consecuencias del uso de un esquema ineficaz de tratamiento antibiótico y la necesidad de evaluar la sensibilidad a los antibióticos en diferentes sitios anatómicos del estómago. La resistencia múltiple limita el número de antibióticos útiles para erradicar H. pylori.

Descargas

La descarga de datos todavía no está disponible.
  • Azucena Arévalo Laboratorio de Bacteriología Especial, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia; Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional de Colombia, Bogotá, D.C., Colombia http://orcid.org/0000-0001-9074-1010
  • William Alberto Otero Unidad de Gastroenterología, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, D.C., Colombia
  • Alba Alicia Trespalacios Laboratorio de Bacteriología Especial, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia

Referencias

Otero W, Gómez M, Castro D. Gastric carcinogenesis. Revista Colombiana de Gastroenterología. 2009;24:314-29.

IARC Helicobacter pylori Working Group. Helicobacter pylori eradication as a strategy for preventing gastric cancer. Lyon: International Agency for Research in Cancer; 2014. p. 1-59.

Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64:1-15. https://doi.org/10.1136/gutjnl-2015-309252

Malfertheiner P, Megraud F, Morain CAO, Gisbert JP, Kuipers EJ, Axon AT, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66:6-30. https://doi.org/10.1136/gutjnl-2016-312288

Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: A systematic review and meta-analysis in World Health Organization Regions. Gastroenterology. 2018 Gastroenterol. 2018;155:1372-82. https://doi.org/10.1053/j.gastro.2018.07.007

Zhang M. High antibiotic resistance rate: A difficult issue for Helicobacter pylori eradication treatment. World J Gastroenterol. 2015;21:13432-7. https://doi.org/10.3748/wjg.v21.i48.13432

Organización Mundial de la Salud. La OMS publica la lista de las bacterias para las que se necesitan urgentemente nuevos antibióticos. Fecha de consulta: 13 de octubre de 2018. Disponible en: http://www.who.int/es/news-room/detail/27-02-2017-who-publishes-list-ofbacteria-for-which-new-antibiotics-are-urgently-needed

Hu Y, Zhang M, Lu B, Dai J. Helicobacter pylori and antibiotic resistance, a continuing and intractable problem. Helicobacter. 2016;21:349-63. https://doi.org/10.1111/hel.12299

Wueppenhorst N, Stueger HP, Kist M, Glocker E. Identification and molecular characterization of triple- and quadruple-resistant Helicobacter pylori clinical isolates in Germany. J Antimicrob Chemother. 2009;63:648-53. https://doi.org/10.1093/jac/dkp003

Otth L, Wilson M, Fernández H, Otth C, Toledo C, Cárcamo V, et al. Isolation of Helicobacter pylori in gastric mucosa and susceptibility to five antimicrobial drugs in southern Chile. Braz J Microbiol. 2011;42:442-7. https://doi.org/10.1590/S1517-83822011000200005

De Francesco V, Giorgio F, Ierardi E, Zotti M, Neri M, Milano A, et al. Primary clarithromycin resistance in Helicobacter pylori: The multicentric Italian clarithromycin resistance observational (MICRO) study. J Gastrointestin Liver Dis. 2011;20:235-9.

Gerrits MM, Schuijffel D, van Zwet AA, Kuipers EJ, Vandenbroucke-Grauls CM, Kusters JG. Alterations in penicillin-binding protein 1A confer resistance to beta-lactam antibiotics in Helicobacter pylori. Antimicrob Agents Chemother. 2002;46:2229-33. https://doi.org/10.1128%2FAAC.46.7.2229-2233.2002

Rimbara E, Noguchi N, Kawai T, Sasatsu M. Mutations in penicillin-binding proteins 1, 2 and 3 are responsible for amoxicillin resistance in Helicobacter pylori. J Antimicrob Chemother. 2008;61:995-8. https://doi.org/10.1093/jac/dkn051

Trespalacios AA, Otero W, Caminos JE, Mercado MM, Ávila J, Rosero LE, et al. Phenotypic and genotypic analysis of clarithromycin-resistant Helicobacter pylori from Bogotá D.C., Colombia. J Microbiol. 2013;51:448-52. https://doi.org/10.1007/s12275-013-2465-6

Kwon DH, Peña JA, Osato MS, Fox JG, Graham DY, Versalovic J. Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates. J Antimicrob Chemother. 2000;46:793-6.

Gerrits MM, Zoete MR De, Arents NL, Kuipers EJ, Kusters JG. 16S rRNA mutation-mediated tetracycline resistance in Helicobacter pylori. Antimicrob Agents Chemother. 2002;46:2996-3000. https://doi.org/10.1128/AAC.46.9.2996–3000.2002

Zhang Z, Liu Z, Zheng P, Tang F, Yang P. Influence of efflux pump inhibitors on the multidrug resistance of Helicobacter pylori. World J Gastrointerol. 2010;16:1279-84. https://doi.org/10.3748/wjg.v16.i10.1279

Kutschke A, de Jonge BLM. Compound efflux in Helicobacter pylori compound efflux in Helicobacter pylori. Antimicrob Agents Chemother. 2005;49:3009-11. https://doi.org/10.1128/AAC.49.7.3009-3010.2005

Falsafi T, Ehsani A, Attaran B, Niknam V. Association of hp1181 and hp1184 genes with the active efflux phenotype in multidrug-resistant isolates of Helicobacter pylori. Jundishapur J Microbiol. 2016;20:e30726. https://doi.org/10.5812/jjm.30726

Liu Z, Zheng P, Yang P. Efflux pump gene hefA of Helicobacter pylori plays an important role in multidrug resistance. World J Gastroenterol. 2008;14:5217-22. https://doi.org/10.3748/wjg.14.5217

Trespalacios AA, Otero Regino W, Mercado Reyes M. Helicobacter pylori resistance to metronidazole, clarithromycin and amoxicillin in Colombian patients. Revista Colombiana de Gastroenterología. 2010;25:31-8.

Trespalacios AA, Otero W, Arévalo GA, Poutou RA, Rimbara E, Graham DY. Surveillance of levofloxacin resistance in Helicobacter pylori isolates in Bogotá-Colombia (2009-2014). PLoS ONE. 2016;11:1-10. https://doi.org/10.1371/journal.pone.0160007

Heep M, Kist M, Strobel S, Beck D, Lehn N. Secondary resistance among 554 isolates of Helicobacter pylori after failure of therapy. Eur J Clin Microbiol Infect Dis. 2000;19:538-41.

Boltin D, Ben-Zvi H, Perets TT, Kamenetsky Z, Samra Z, Dickman R, et al. Trends in secondary antibiotic resistance of Helicobacter pylori from 2007 to 2014: Has the tide turned? J Clin Microbiol. 2015;53:522-7. https://doi.org/10.1128/JCM.03001-14

Rugge M, Correa P, Di Mario F, El-Omar E, Fiocca R, Geboes K, et al. OLGA staging for gastritis: A tutorial. Dig Liver Dis. 2008;40:650-8. https://doi.org/10.1016/j.dld.2008.02.030

Patel JB, Cockerill III FR, Alder J, Bradford PA, Eliopoulos GM, Hardy DJ, et al. Performance standards for antimicrobial susceptibility testing; Twenty-Fourth Informational Supplement. Wayne: CLSI; 2014. p. 1-230.

Wikler MA, Bush K, Cockerill III FR, Dudley MN, Eliopoulos GM, Hardy DJ, et al. Performance standards for antimicrobial susceptibility testing; Eighteenth Informational Supplement. Wayne: CLSI; 2008. p. 1-188.

Mégraud F. Antibiotic resistance in Helicobacter pylori infection. Br J Bull. 1998;54:207-16.

Mégraud F, Bénéjat L, Nina E, Ngoyi O, Lehours P. Molecular approaches to identify Helicobacter pylori antimicrobial resistance. Gastroenterol Clin North Am. 2015;44:577-96. https://doi.org/10.1016/j.gtc.2015.05.002

Mégraud F, Lehours P. Helicobacter pylori detection and antimicrobial susceptibility testing. Clin Microbiol Rev. 2007;20:280-322. https://doi.org/10.1128/CMR.00033-06

Glocker E, Stueger H, Kist M. Quinolone resistance in Helicobacter pylori isolates in Germany. Antimicrob Agents Chemother. 2007;51:346-9. https://doi.org/10.1128/AAC.00614-06

Kim KS, Kang JO, Eun CS, Han DS, Choi TY. Mutations in the 23S rRNA gene of Helicobacter pylori associated with clarithromycin resistance. J Korean Med Sci. 2002;17:599-603. https://doi.org/10.3346/jkms.2002.17.5.599

Tankovic J, Lascols C, Sculo Q, Petit J. Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pylori. Antimicrob Agents Chemother. 2003;47:3942-4. https://doi.org/10.1128/AAC.47.12.3942-3944.2003

Ogata SK, Godoy APO, da Silva Patricio FR, Kawakami E. High Helicobacter pylori resistance to metronidazole and clarithromycin in Brazilian children and adolescents. J Pediatr Gastroenterol Nutr. 2013;56:645-8. https://doi.org/10.1097/MPG.0b013e31828b3669

Mégraud F. Current recommendations for Helicobacter pylori therapies in a world of evolving resistance. Gut Microbes. 2013;4:541-8. https://doi.org/10.4161/gmic.25930

Boyanova L. Prevalence of multidrug-resistant Helicobacter pylori in Bulgaria. J Med Microbiol. 2009;58:930-5. https://doi.org/10.1099/jmm.0.009993-0

Karczewska E, Wojtas-bonior I, Sito E, Budak A. Primary and secondary clarithromycin, metronidazole, amoxicillin and levofloxacin resistance to Helicobacter pylori in southern Poland. Pharmacol Rep. 2011;63:799-807.

Park CS, Lee SM, Park CH, Koh HR, Jun CH, Park SY, et al. Pretreatment antimicrobial susceptibility-guided vs. clarithromycin-based triple therapy for Helicobacter pylori eradication in a region with high rates of multiple drug resistance. Am J Gastroenterol. 2014;109:1595-602. https://doi.org/10.1038/ajg.2014.222

Selgrad M, Tammer I, Langner C, Bornschein J, Meißle J, Kandulski A, et al. Different antibiotic susceptibility between antrum and corpus of the stomach, a possible reason for treatment failure of Helicobacter pylori infection. World J Gastroenterol. 2014;20:16245-51. https://doi.org/10.3748/wjg.v20.i43.16245

Yakoob J, Fan X, Hu G, Yang H, Liu L, Liu S, et al. Polycolonization of Helicobacter pylori among Chinese subjects. Clin Microbiol Infect. 2001;7:187-92. https://doi.org/10.1046/j.1198-743x.2001.00226.x

Kim JJ, Kim JG, Kwon DH. Mixed-infection of antibiotic susceptible and resistant Helicobacter pylori isolates in a single patient and underestimation of antimicrobial susceptibility testing. Helicobacter. 2003;8:202-6. https://doi.org/10.1046/j.1523-5378.2003.00145.x

Otero W, Gómez M, Otero L,Trespalacios A. Helicobacter pylori: ¿cómo se trata en el 2018? Rev Gastroenterol Peru. 2018;38:54-63.

Otero W, Trespalacios AA, Otero L, Vallejo M, Torres M, Pardo R, et al. Guía práctica para el diagnóstico y tratamiento de la infección por Helicobacter pylori en adultos. Revista Colombiaba de Gastroenterología. 2015;30(Suppl.1):17-33.

Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: Evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014;12:177-86. https://doi.org/10.1016/j.cgh.2013.05.028

Wu IT, Chuah SK, Lee CH, Liang CM, Lu LS, Kuo YH, et al. Five-year sequential changes in secondary antibiotic resistance of Helicobacter pylori in Taiwan. World J Gastroenterol. 2015;21:10669-74. https://doi.org/10.3748/wjg.v21.i37.10669

Boyanova L, Evstatiev I, Gergova G, Yaneva P, Mitov I. Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance. Int J Antimicrob Agents. 2015;46:703-6. https://doi.org/10.1016/j.ijantimicag.2015.08.010

Shi J, Jiang Y, Zhao Y. Promising in vitro and in vivo inhibition of multidrug-resistant Helicobacter pylori by linezolid and novel oxazolidinone analogues. J Glob Antimicrob Resist. 2016;7:106-9. https://doi.org/10.1016/j.jgar.2016.07.016

Cómo citar
Arévalo, A., Otero, W. A., & Trespalacios, A. A. (2019). Helicobacter pylori: resistencia múltiple en pacientes de Bogotá, Colombia. Biomédica, 39, 125-134. https://doi.org/10.7705/biomedica.v39i3.4437
Publicado
2019-05-01