Tratamiento de primera línea para erradicación de Helicobacter pylori: todavía una terapia eficaz / First-line treatment for eradication of Helicobacter pylori: Still an effective therapy

Resumen Objetivo: Este estudio tiene como objetivo principal determinar la respuesta al esquema de tratamiento de primera línea con triple terapia estándar (amoxicilina, claritromicina, omeprazol), para erradicación de Helicobacter pylori en una determinada población, para determinar si este esquema propuesto en guías internacionales es aún una opción adecuada para pacientes en una determinada región de Costa Rica. Métodos: Se realizó una búsqueda en el servicio de gastroenterología del Hospital San Francisco de Asís, Grecia, Alajuela, Costa Rica; de todos los pacientes con infección por Helicobacter pylori y que recibieron tratamiento de primera línea con triple terapia (amoxicilina, claritromicina y omeprazol) por 14 días, en el periodo comprendido entre febrero 2017 a febrero 2019, incluyendo para el análisis solamente en los que se contaba con una prueba confirmatoria posterior a tratamiento, ya fuera por antígeno fecal de H. pylori o biopsia convencional. Resultados: Se identificaron un total de 369 casos. El diagnóstico se realizó con biopsia en el 96,4% de los pacientes. La respuesta al tratamiento de primera línea se alcanzó en un 90.5% corroborada por antígeno fecal en el 92.1% de los casos. Conclusiones: Este estudio muestra que la terapia triple con amoxicilina, claritromicina e Inhibidor de bomba de protones por 14 días mantiene un adecuado nivel de eficacia. Sin embargo, hay que tomar en cuenta que estos datos son únicamente de un área de atracción determinada y puede que no reflejen la realidad de todo el país.

Abstract Aim: The main objective of this study is to determine the response to the firstline treatment regimen with triple standard therapy (amoxicillin, clarithromycin, omeprazole), to eradicate Helicobacter pylori in a certain population. The goal is to determine if the proposed regimen in international guidelines services is still a suitable option for patients in a certain region of Costa Rica. Methods: The study took place in San Francisco de Asís Hospital, Grecia, Alajuela, Costa Rica. All patients with a Helicobacter pylori infection that were given first- line treatment with triple therapy (amoxicillin, clarithromycin and omeprazole) for its eradication for 14 days, in the period between February of 2017 and February of 2019, were included in the study. Results: A total of 369 cases were identified. The diagnosis was made with biopsy in 96.4% of patients. Response to first-line treatment was achieved in 90.5% corroborated by fecal antigen in 92.1% of all cases. Conclusions: This study shows that triple therapy with amoxicillin, clarithromycin and omeprazole for 14 days maintains an adequate level of efficacy. However, it must be considered that these results are from a specific area and may not reflect the reality of the entire country.

Comportamiento clínico epidemiológico del cáncer gástrico en el Hospital Calixto García / Clinical-Epidemiological Characteristics of Gastric Cancer in Calixto Garcia Hospital

Introducción: El cáncer de estómago representa la segunda causa de muerte relacionada con neoplasias en el mundo, es responsable del 8 al 10 por ciento de todas las muertes por cáncer. A pesar de un marcado descenso en su incidencia, constituye una de las principales causas de muerte por cáncer en Cuba y el mundo. Objetivo: Describir el comportamiento clínico epidemiológico en los pacientes con cáncer gástrico. Métodos: Se realizó un estudio observacional, descriptivo, transversal de los pacientes con diagnóstico de cáncer gástrico que acudieron a consulta en el Hospital Universitario General Calixto García, en el período comprendido entre enero de 2014 y diciembre de 2018. El universo estuvo constituido por 146 pacientes. Los datos fueron obtenidos de las historias clínicas y procesados mediante estadística descriptiva. Resultados: De los pacientes estudiados, 67,6 por ciento pertenecían al sexo masculino y tenían entre 60 y 79 años; 51,7 por ciento presentó como factor de riesgo el hábito de fumar. Un total de 124 pacientes padecieron de dolor abdominal. El 100 por ciento de los exámenes complementarios realizados fueron endoscopia y biopsia. Se observó el adenocarcinoma moderadamente diferenciado en un total de 80 pacientes. Al 100 por ciento se le realizó tratamiento quirúrgico. La técnica quirúrgica más empleada fue la gastrectomía subtotal. Conclusiones: Las edades avanzadas de la vida, los antecedentes de úlcera gástrica, el tabaquismo y el alcoholismo son factores epidemiológicos característicos de la población de enfermos aquejados de cáncer gástrico. Los elementos clínicos identificados fueron los habitualmente descritos en la literatura médica. La cirugía en la actualidad es la única modalidad con potencial curativo(AU)

Introduction: Stomach cancer accounts for the second cause of death related to neoplasms worldwide; it is responsible for 8 percent to 10 percent of all cancer deaths. In spite of a marked decrease in its incidence, it constitutes one of the main causes of cancer death in Cuba and worldwide. Objective: To describe the clinical-epidemiological characteristics of patients with gastric cancer. Methods: An observational, descriptive and cross-sectional study was carried out with patients with a diagnosis of gastric cancer who attended consultation at Calixto García General University Hospital in the period from January 2014 to December 2018. The universe consisted of 146 patients. The data were obtained from medical records and processed by descriptive statistics. Results: Of the patients studied, 67.6 percent were male and aged 60-79 years. 51.7 percent presented smoking as a risk factor. A total of 124 patients suffered from abdominal pain. 100 percent of the complementary examinations performed were endoscopy and biopsy. Moderately differentiated adenocarcinoma was observed in a total of 80 patients. The surgical treatment was performed in 100 percent. The most commonly used surgical technique was subtotal gastrectomy. Conclusions: The research suggests that, currently, early diagnosis and surgery is the only modality with curative potential, being able to raise the quality of life, as well as to improve morbidity and mortality rates in the population(AU)

Caracterización clínico-histopatológica de la gastritis crónica / Clinical-histopathological characterization of chronic gastritis

La gastritis es una enfermedad con una alta morbilidad a nivel mundial, el principal factor de riesgo es la infección por Helicobacter pylori. Objetivo: Describir las características clínicas, histopatológica y endoscópicas en una población con gastritis crónica. Material y métodos: Se realizó un estudio observacional de tipo descriptivo, retrospectivo, se incluyeron 49 pacientes que acudieron a la consulta externa del área de gastroenterología, de 18 a 65 años, a quienes se realizó el estudio histopatológico y endoscópico en el Servicio de Gastroenterología en el Hospital General Quevedo, de Los Ríos-Ecuador, durante septiembre 2017 ­ septiembre 2018. Resultados: Se observó predominio del género masculino (65%); en mayores de 40 años (55%), la epigastralgía y la sensación de acidez estomacal, 39% y 35% respectivamente, fueron los síntomas más frecuentes, La positividad para Helicobacter pylori, alcanzó el 86%, y la lesión no erosiva un 73%, existió mayor presencia de la forma no atrófica (84%) sobre la atrófica. Conclusiones: La gastritis crónica predominó en el grupo etario mayor a 40 años y de género masculino, siendo los factores de riesgo de mayor prevalencia la infección por Helicobacter pylori y los asociados al consumo de antiinflamatorios no esteroideos, mala alimentación, alcohol y tabaco, los síntomas como epigastralgía y la sensación de acidez estomacal fueron los más frecuentes. El hallazgo endoscópico fue mayor para las formas no erosivas, y de acuerdo a la histopatología la gastritis no atrófica antral moderada fue la más frecuente(AU)

Gastritis is a disease with high morbidity worldwide, the main risk factor is Helicobacter pylori infection. Objective: To describe the clinical, histopathological and endoscopic characteristics in a population with chronic gastritis. Material and methods: An observational, descriptive, retrospective study was carried out, including 49 patients who attended the outpatient consultation of the gastroenterology area, aged 18 to 65 years, who underwent a histopathological and endoscopic study in the Gastroenterology Service at the Quevedo General Hospital, Los Ríos-Ecuador, during September 2017 - September 2018. Results: A predominance of the male gender was observed (65%); In people over 40 years of age (55%), epigastralgia and the sensation of heartburn, 39% and 35% spectively, were the most frequent symptoms, the positivity for Helicobacter pylori, reached 86%, and the non-erosive lesion 73 %, there was a greater presence of the non-atrophic form (84%) over the atrophic one. Conclusions: Chronic gastritis predominated in the age group over 40 years of age and male, the most prevalent risk factors being Helicobacter pylori infection and those associated with the consumption of non-steroidal anti-inflammatory drugs, poor diet, alcohol and tobacco. symptoms such as epigastric pain and the sensation of heartburn were the most frequent. The endoscopic finding was greater for non-erosive forms, and according to histopathology, moderate antral non-atrophic gastritis was the most frequent(AU)

Guía de práctica clínica para el diagnóstico y manejo de la infección por Helicobacter Pylori en enfermedades gastroduodenales / Clinical practice guideline for the diagnosis and management of Helicobacter Pylori infection in gastroduodenal diseases

La infección por Helicobacter pylori (HP) es la infección crónica más común en humanos (1, 2). Se trata de una bacteria gram negativa espiralada, microaerofílica (3) que por su contenido en ureasa, motilidad y capacidad para adherirse al epitelio gástrico puede sobrevivir y proliferar en el medio gástrico (4). Esta bacteria generalmente no invade el tejido gástrico, pero lo hace más susceptible al daño del ácido péptico al romper la capa mucosa y liberar enzimas y toxinas que, al ser reconocidas por el huésped, generan una reacción inflamatoria más perjudicial aún. La inflamación crónica del tejido altera la fisiología de la secreción gástrica y produce una gastritis crónica que en muchos casos no causa síntomas ni progresa, pero en otros, produce úlcera péptica, o gastritis atrófica que luego avanza a metaplasia intestinal y eventualmente a carcinoma gástrico (5-7). La prevalencia de infección por HP a nivel global es estimada en alrededor de 50% de la población, en el Perú, esta cifra llega al 45.5% (8). Debido a la alta prevalencia de la infección y las complicaciones de la misma es necesario realizar una Guía de Práctica Clínica que optimice el diagnóstico y manejo de esta infección. Por ello, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia para gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Carcinoma gástrico: revisión bibliográfica / Gastric Carcinoma: literature review

Resumen El carcinoma gástrico hoy en día es una de las principales causas de mortalidad a nivel mundial por neoplasias y especialmente en países como Costa Rica, que se cataloga como un país de alta incidencia. Existen múltiples factores de riesgo, siendo el primero y más importante la infección por Helicobacter pylori, que desencadena una cascada de diferentes lesiones, iniciando en atrofia gástrica, que puede llegar a finalizar en cáncer invasivo. Existen otros factores que pueden influir en un ambiente pro-carcinogénico tales como fumado, obesidad, la dieta, entre otros. Múltiples naciones han desarrollado diferentes guías de tamizaje para disminuir la mortalidad; sin embargo, en países con alta incidencia sigue siendo el estándar realizar estudios de imagen y endoscopia luego de determinada edad dependiendo de factores de riesgo.

Abstract Gastric carcinoma is nowadays one of the main causes of mortality worldwide due to neoplasms and especially in countries such as Costa Rica, which is classified as a high incidence country. There are multiple risk factors, starting with Helicobacter pylori infection being the most important one; after the infection a cascade with different lesions is triggered, first it begins with gastric atrophy and then eventually lead to an invasive cancer. There are other factors that can influence a pro-carcinogenic environment such as smoking, obesity, diet, among others. Multiple nations have developed different screening guidelines to reduce mortality, however in countries with high incidence it is still the gold-standard to perform imaging and endoscopy studies after a certain age and depending on risk factors.

Brazilian Green Propolis: Chemical Composition of Essential Oil and Their In Vitro Antioxidant, Antibacterial and Antiproliferative Activities

Abstract Propolis is a resinous substance collected and processed by Apis mellifera from parts of plants, buds and exudates. In Minas Gerais (MG) state, Brazil, green propolis is produced from the collection of resinous substance found in shoot apices of Baccharis dracunculifolia. This paper aims to investigate the chemical composition and in vitro antioxidant, anti-Helicobacter pylori, antimycobacterial and antiproliferative activities of essential oil (EO) from Brazilian green propolis (BGP-EO). The oil showed high antibacterial activity against H. pylori (MIC = 6.25 µg/mL), Mycobacterium avium (MIC = 62.5 µg/mL) and M. tuberculosis (MIC = 64 µg/mL). Its antioxidant activity was evaluated in vitro by both DPPH (IC50 = 23.48 µg/mL) and ABTS (IC50 = 32.18 µg/mL) methods. The antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor cell lines (MCF-7, HeLa and M059J) was analyzed by the XTT assay. BGP-EO showed inhibition of normal cell growth at 68.93 ± 2.56 µg/mL. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were 56.17, 66.43 and -65.83 µg/mL for MCF-7, HeLa and M059J cells, respectively. Its major constituents, which were determined by GC-FID and GC-MS, were carvacrol (20.7 %), acetophenone (13.5 %), spathulenol (11.0 %), (E)-nerolidol (9.7 %) and β-caryophyllene (6.2 %). These results showed the effectiveness of BGP-EO as a natural product which has promising biological activities.

Vigilância da resistência a antibióticos contra o Helicobacter pylori na região do Biobío (Chile) em uma década / Antibiotic resistance surveillance of helicobacter pylori at the biobío region (chile) in a decade

ABSTRACT BACKGROUND: Helicobacter pylori infection in Chile remains as a public and private health-care system's challenge, with a prevalence of the infection over 70%. Nowadays, antibiotic treatment of the infection is mandatory to prevent the arising of severe associated diseases but failures in the eradication therapy mainly due to clarithromycin resistance has been observed worldwide and first line eradication therapy seems to be not effective anymore in several geographical areas. Thus, health-care systems are committed to maintain an epidemiological surveillance upon the evolution of the antibiotic resistance of this priority 2 pathogen. OBJECTIVE: This work reports a 10 years surveillance of the primary antibiotic resistance of H. pylori clinical isolates at the Biobío region-Chile, and the evolution of resistance toward amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline among the species. METHODS: H. pylori strains were investigated during the periods 2005-2007 (1435 patients analysed) and 2015-2017 (220 patients analysed) by inoculating a saline homogenate biopsy onto the surface of Columbia agar (Oxoid, Basingstoke, UK) - supplemented with 7% horse red blood cells plus DENT inhibitor (Oxoid, Basingstoke, UK) - following by incubation at 37ºC under 10% CO2 atmosphere for five days. Antibiotic resistance pattern of the isolates was assessed using the disk diffusion test in Müeller-Hinton agar supplemented with 7% horse red blood cells followed by incubation for further three days under 10% CO2 atmosphere. Statistical analysis was done using the SPSS v22 software and P values <0.05 were considered statistically significant. RESULTS: A total of 41% of 1435 patients were detected to be infected with H. pylori by bacteriological culture in 2005-2007 period, meanwhile 32.7% from 220 patients were also infected in 2015-2017 period. The clinical isolates of H. pylori are mostly susceptible to amoxicillin and tetracycline (both over 98% of strains), but less susceptible to levofloxacin in both periods analysed (over 79% of the strains). On the other hand, metronidazole continuous showing the highest score of resistant isolates (over 40% of resistant strains), although an 18% fewer resistant strains were observed in 2015-2017 period. Clarithromycin, the key antibiotic in eradication therapies, has an increased frequency of resistant strain isolated in the decade (22.5% in 2005-2007 and 29.2% in 2015-2017). Multidrug resistant strains (two, three and four antibiotics) were also detected in both periods with the highest scores for simultaneous resistance to clarithromycin-metronidazole (18%) and clarithromycin-metronidazole-levofloxacin (12.5%) resistant strains. According to gender, the isolates resistant to amoxicillin, clarithromycin and metronidazole were more frequent in female, with a specific increment in amoxicillin and clarithromycin resistance. CONCLUSION: The frequency of clarithromycin resistance (29.2%) detected in 2015-2017 suggests that conventional triple therapy is no longer effective in this region.

RESUMO CONTEXTO: A infecção por Helicobacter pylori no Chile permanece como um desafio do sistema de saúde público e privado, com prevalência da infecção acima de 70%. Hoje em dia, o tratamento antibiótico da infecção é obrigatório para prevenir o surgimento de graves doenças associadas, mas falhas na terapia de erradicação, principalmente devido à resistência à claritromicina, têm sido observadas em todo o mundo, e a terapia de erradicação de primeira linha parece não ser mais eficaz em várias áreas geográficas. Assim, os sistemas de saúde estão comprometidos em manter uma vigilância epidemiológica sobre a evolução da resistência aos antibióticos deste patógeno prioritário tipo 2. OBJETIVO: Este trabalho relata uma vigilância de 10 anos da resistência antibiótica primária de isolados clínicos de H. pylori na região do Biobío-Chile, e a evolução da resistência em relação à amoxicilina, claritromicina, levofloxacina, metronidazol e tetraciclina entre as espécies. MÉTODOS: As cepas de H. pylori foram investigadas durante os períodos 2005-2007 (1435 pacientes analisados) e 2015-2017 (220 pacientes analisados) inoculando uma biópsia de homogeneizado fisiológico na superfície do agar Columbia (Oxoid, Basingstoke, Reino Unido) - suplementado com 7% de glóbulos vermelhos do cavalo mais o inibidor de DENTE (Oxoid, Basingstoke, Reino Unido) - seguindo pela incubação em 37ºC a atmosfera de 10% de CO2 por cinco dias. O padrão de resistência aos antibióticos dos isolados foi avaliado utilizando-se o teste de difusão em disco em agar Müeller-Hinton suplementado com 7% de glóbulos vermelhos de cavalo seguidos de incubação por mais três dias a atmosfera de 10% de CO2. A análise estatística foi realizada utilizando-se o software SPSS V22 e os valores de P<0,5 foram considerados estatisticamente significantes. RESULTADOS: Um total de 41% dos 1435 pacientes foram detectados como contaminados por H. pylori pela cultura bacteriológica no período 2005-2007, ao mesmo tempo 32,7% de 220 pacientes foram contaminados igualmente no período 2015-2017. Os isolados clínicos de H. pylori são principalmente suscetíveis à amoxicilina e tetraciclina (tanto mais de 98% das cepas), mas menos suscetíveis à levofloxacina em ambos os períodos analisados (mais de 79% das cepas). Por outro lado, o metronidazol permaneceu mostrando a maior pontuação de resistentes isolados (mais de 40% de cepas resistentes), embora tenham sido observados 18% menos cepas resistentes no período de 2015-2017. A claritromicina, o antibiótico-chave em terapias de erradicação, tem uma frequência aumentada de cepa resistente isolada na década (22,5% em 2005-2007 e 29,2% em 2015-2017). Cepas multirresistentes (dois, três e quatro antibióticos) também foram detectadas em ambos os períodos com os maiores escores de resistência simultânea à claritromicina-metronidazol (18%) e claritromicina-metronidazol-levofloxacina (12,5%) cepas resistentes. De acordo com o sexo, os isolados resistentes à amoxicilina, claritromicina e metronidazol foram mais frequentes no sexo feminino, com incremento específico em amoxicilina e resistência à claritromicina. CONCLUSÃO: A frequência de resistência à claritromicina (29,2%) detectada em 2015-2017 sugere que a terapia tripla convencional não é mais efetiva nesta região.

Mutaciones del gen ARN ribosómico 23S de Helicobacter pylori asociadas con resistencia a claritromicina en pacientes atendidos en una unidad de endoscopia de Medellín, Colombia / Mutations in the Helicobacter pylori 23S rRNA gene associated with clarithromycin resistance in patients at an endoscopy unit in Medellín, Colombia

Resumen Introducción. La claritromicina es el antibiótico de primera línea para el tratamiento de la infección por Helicobacter pylori. La resistencia bacteriana se produce principalmente por mutaciones puntuales del gen ARN ribosómico 23S (ARNr 23S). Objetivo. Determinar la frecuencia de las mutaciones puntuales A2143G y A2142G del gen ARNr 23S asociadas con la resistencia de H. pylori a la claritromicina en muestras de pacientes con manifestaciones dispépticas en Medellín, región noroccidental de Colombia. Materiales y métodos. Se extrajo ADN a partir de muestras de biopsia gástrica obtenidas de pacientes con manifestaciones dispépticas atendidos en una unidad de endoscopia entre el 2016 y el 2017. Mediante reacción en cadena de la polimerasa (PCR), se amplificaron las regiones s y m del gen vacA y una región del gen ARNr 23S bacteriano. La presencia de las mutaciones A2142G y A2143G se determinó por la técnica de polimorfismos de longitud de fragmentos de restricción (RFLP) con las enzimas BbsI y BsaI, respectivamente. Resultados. Se encontró una prevalencia de infección de 44,2 % (175/396), según el informe de histopatología. En 143 de estas 175 muestras positivas se amplificaron las tres regiones del genoma bacteriano. Se identificaron las mutaciones A2143G y A2142G en 27 muestras (18,8 %; 27/143), la mutación más frecuente fue la A2143G (81,5 %; 22/27). Conclusiones. Hubo una gran prevalencia de mutaciones asociadas con la resistencia de H. pylori a la claritromicina en la población de estudio. Se requieren estudios adicionales para establecer la resistencia bacteriana en la población colombiana y, así, determinar los tratamientos de primera línea y de rescate.

Abstract Introduction: Clarithromycin is the first-line antibiotic for the treatment of Helicobacter pylori infection. Bacterial resistance is mainly due to the presence of specific mutations in the 23S ribosomal RNA (rRNA) gene. Objective: To determine the frequency of A2143G and A2142G specific mutations in the 23S rRNA gene associated with clarithromycin resistance of H. pylori in samples from patients with dyspeptic manifestations in Medellín, northwestern Colombia. Materials and methods: DNA was extracted from gastric biopsy samples of patients with dyspeptic manifestations seen at an endoscopy unit in Medellín between 2016 and 2017. PCR was performed to amplify the bacterial s and m vacA regions, and a region in the 23S rRNA gene. The presence of the A2142G and A2143G mutations was determined using the restriction fragment length polymorphism (RFLP) technique with the BbsI and BsaI enzymes, respectively. Results: The prevalence of infection was 44.2% (175/396), according to the histopathology report. The positive samples were analyzed and the three regions of the bacterial genome were amplified in 143 of the 175 samples. The A2143G and A2142G mutations were identified in 27 samples (18.8%, 27/143). The most frequent mutation was A2143G (81.5%, 22/27). Conclusions: We found a high prevalence of H. pylori mutations associated with clarithromycin resistance in the study population. Further studies are required to determine the bacterial resistance in the Colombian population in order to define first line and rescue treatments.

Susceptibilidad antimicrobiana y mutaciones en el gen ARNr 23S de Helicobacter pylori en pacientes dispépticos / Antimicrobial susceptibility and mutations in the 23S rRNA gen of Helicobacter pylori in dyspeptic patients

RESUMEN Con el objetivo de evaluar la susceptibilidad antimicrobiana y detectar mutaciones puntuales en el gen ARNr 23S en cepas de Helicobacter pylori se realizó un estudio transversal que incluyó a 95 pacientes con dispepsia atendidos en una clínica privada de Lima. Mediante endoscopía se colectaron biopsias de antro para el aislamiento de cepas de Helicobacter pylori para la evaluación de la susceptibilidad antimicrobiana empleando la técnica de microdilución en caldo. La detección de mutaciones puntuales se desarrolló mediante PCR-RFLP. El porcentaje de infección por Helicobacter pylori fue de 46,3%, se observaron valores de resistencia de 52,3% a claritromicina, 29,6% a metronidazol, 45,5% a levofloxacino y 4,6% a amoxicilina. El porcentaje de mutaciones puntuales A2142G y A2143G asociados a resistencia a claritromicina fue 43,5%. En conclusión, encontramos que las tasas de resistencia antimicrobiana y el porcentaje de cepas de Helicobacter pylori circulantes en una clínica privada de Lima fueron elevadas.

ABSTRACT In order to evaluate antimicrobial susceptibility and detect specific mutations in the 23S rRNA gene in Helicobacter pylori strains, a cross-sectional study was performed on 95 patients with dyspepsia treated in a private clinic in Lima. Antrum biopsies were collected by endoscopy for isolation and evaluation of antimicrobial susceptibility using the broth microdilution method. The detection of specific mutations was developed by PCR-RFLP. The percentage of infection by Helicobacter pylori was 46.3%. Resistance values of 52.3% to clarithromycin, 29.6% to metronidazole, 45.5% to levofloxacin, and 4.6% to amoxicillin were observed. The percentage of specific A2142G and A2143G mutations associated with clarithromycin resistance was 43.5%. In conclusion, we found that antimicrobial resistance rates and the percentage of Helicobacter pylori strains circulating in a private clinic in Lima were high.

Helicobacter pylori: resistencia múltiple en pacientes de Bogotá, Colombia / Helicobacter pylori: Multiple resistance in patients from Bogotá, Colombia

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.

Abstract Introduction: The main cause for Helicobacter pylori infection treatment failure is antibiotic resistance, where clarithromycin and metronidazole play the main role. In Colombia, primary resistance as a consequence of the use of these two antibiotics and excessive levofloxacin use is above the accepted limit (13.6%, 83%, and 16%, respectively). Despite this fact, empirical therapies that include the combination of these antibiotics are used in patients with previous therapeutic failure. Objective: To determine antibiotic resistance in patients previously treated for H. pylori in Bogotá, Colombia. Materials and methods: We conducted a descriptive study that included ten isolates obtained from five patients with three or four previous failed treatments for H. pylori. Antibiotic resistance to amoxicillin, clarithromycin, levofloxacin, and metronidazole was investigated by agar dilution and confirmed by DNA sequencing (Magrogen, Korea). Results: Eight isolates were resistant to two or more antibiotics. All isolates were resistant to levofloxacin. Susceptibility patterns in isolates from the gastric antrum and the body of the stomach were different in three patients. Conclusion: As far as we know, this is the first evidence of multiple H. pylori resistance in Colombia in previously treated patients. Results demonstrated the consequences of using an ineffective antibiotic scheme and the need to assess antibiotic susceptibility in different anatomical sites of the stomach. The consequences of multiple resistance decrease possible antibiotic effectiveness to eradicate H. pylori in the future.

Anti-Helicobacter pylori and Anti-inflammatory Properties of Eugenia uniflora L

Abstract Helicobacter pylori is a bacterium that reaches half of the world population and it's recognized as the main cause of chronic gastritis and peptic ulcer. In this study, we evaluated the anti-H. pylori, antioxidant and immunomodulatory activities of the methanolic (MeOH) extract of Eugenia uniflora leaves and chemical profile. Anti-H. pylori activity was evaluated by spectrophotometric broth microdilution technique by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), in addition to the evaluation of the effect on the urease enzyme. The antioxidant activity was evaluated by capturing O2 •-, HOCl e NO• radicals. The immunomodulatory effect was evaluated on the cytokines TNF-α, IL-6 and on nitric oxide through inhibition in LPS-stimulated macrophages. The chemical profile was performed by total phenolic, tannin and flavonoid contents and mass spectrometry analysis by ESI-FT-ICR MS. In the anti-H. pylori assay the extract showed MIC of 128 μg/mL, however it did not obtain MBC. The extract also showed ability to inhibit the urease enzyme about 20%. The antioxidant activity of the MeOH extract showed EC50 values of 29.77 µg/mL, 15.71 µg/mL and 442.10 µg/mL to O2 •-, HOCl and NO•, respectively. The extract also showed influence on the release of TNF-α, IL-6 and NO in LPS-stimulated macrophages, ranging from 39% to 97% inhibition. Flavonoids, phenylpropanoids, tannins, triterpenoids and carbohydrates were the major classes of compounds present in the MeOH extract as identified by (-)-ESI-FT-ICR MS. The results indicate important anti-H. pylori, antioxidant and immunomodulatory activities from Eugenia uniflora highlighting its importance in the prevention and treatment of diseases caused by H. pylori infection.

Erradicación de Helicobacter pylori, consideraciones clínicas según la edad / Helicobacter pylori eradication, clinical considerations related to age

Helicobacter pylori (H. pylori) is a gram negative bacteria that survives in the gastric acid environment. The infection is acquired mainly during childhood. Fifty to 70% of adult population has the infection. However, in the last 10 year, a decrease in the prevalence of this infection has been observed in all age groups, in particular in pediatric population and elderly patients over 60 years old. The evolution of the infection depends on bacterial factors (virulence and toxins) and host immune response. People infected mainly develop gastrointestinal diseases such as gastritis, peptic ulcer and MALT lymphoma. H. pylori infection is the main risk factor of gastric cancer and for that reason, the eradication is recommended if H. pylori has been detected through invasive or non-invasive tests. Among children, eradication is not recommended unless there is a clinical manifestation that merits. H. pylori eradication is recommended in symptomatic adults and there is a controversy about massive eradication in asymptomatic population due to the risk of development of antibiotic resistance. Treatment is based on the use of proton pump inhibitors (PPI) associated to antibiotics, that should be chosen taking into account the increasing antibiotic resistance, and local availability. Clarithromycin (CLA) and levofloxacin resistance is increasingly high, and CLA-free quadruple therapy schemes are currently recommended for first-line therapy. H. pylori eradication must be confirmed with invasive or non-invasive tests. Second-line therapy based on antibiotics not previously used, PPI high doses and bismuth is recommended.

Helicobacter pylori (H. pylori) es una bacteria gramnegativa que sobrevive en el medio ácido gástrico. La infección se adquiere principalmente en la niñez. Un 50 a 70% de la población adulta es portadora, pero en los últimos 10 años, se ha observado una disminución en la prevalencia de infección en todos los grupos etarios, en particular en población pediátrica y mayores de 60 años. La evolución de la infección depende de factores propios de la bacteria (virulencia, toxinas) y de la respuesta inmune del huésped. Los individuos infectados desarrollan principalmente patologías gastrointestinales como gastritis, úlcera péptica y linfoma MALT. La infección por H. pylori es el principal factor de riesgo del cáncer gástrico por lo que se recomienda su erradicación en caso de haberse detectado mediante test invasivo o no invasivo. En niños, no es recomendable la erradicación a menos que exista una manifestación clínica que lo amerite. Se recomienda su erradicación en adultos sintomáticos y existe controversia respecto a la erradicación masiva en población asintomática debido al riesgo de desarrollar resistencia antibiótica. El tratamiento se basa en el uso de inhibidores de la bomba de protones asociado a antibióticos, los cuales deben ser escogidos teniendo en cuenta la tasa de resistencia antimicrobiana y disponibilidad local. La resistencia a claritromicina (CLA) y levofloxacino es creciente, por lo que se recomienda el uso de esquemas de cuadriterapia libre de CLA en esquemas de primera línea. Se recomienda confirmar su erradicación con test no invasivos y retratar con esquema de segunda línea con antibióticos no utilizados previamente, asociado a dosis altas de inhibidores de bomba de protones y sales de bismuto.

Usefulness of rapid urease test samples for molecular analysis of clarithromycin resistance in Helicobacter pylori / Utilidad de las muestras de test rápido de ureasa para el análisis molecular de resistencia a claritromicina en Helicobacter pylori

Helicobacter pylori is a gastric pathogen that is widely recognized as a causative agent of gastric disease. Its eradication is variable, mainly due to increased resistance to clarithromycin. Our objective was: to evaluate (i) if the biopsy specimen used for the rapid urease test is a useful sample to detect resistance to clarithromycin by PCR-RFLP and (ii) the distribution of A2142G and A2143G point mutations in the 23S rRNA gene, in relation to virulence factors in our region. Gastric specimens were collected from adult dyspeptic patients (n = 141) and H. pylori was investigated by the rapid urease test, histopathological analysis and PCR for the hsp60 gene. Clarithromycin resistance was detected by PCR-RFLP in 62 H. pylori (+) paired biopsy specimens submitted to molecular analysis and the rapid urease test. H. pylori virulence factors were analyzed by multiplex PCR using specific primers for the cagA, vacA and babA2 genes. Thirteen out of 62 strains (20.9%) were resistant to clarithromycin: 6/13 (46.2%) harbored the A2143G mutation whereas 7/13 (53.8%) carried the A2142G point mutation. vacA m1s1 was the most frequent genotype among the resistant strains. In conclusion, the biopsy specimens used for the rapid urease test were suitable samples for clarithromycin resistance detection in patients infected with H. pylori, which became especially useful in cases where the number or size of the biopsies is limited. In addition, this is the first report of a molecular analysis for clarithromycin resistance performed directly from gastric biopsies in our region.

Helicobacter pylori es un patógeno ampliamente reconocido como causante de enfermedad gástrica. Su erradicación es variable, principalmente debido al incremento de la resistencia a claritromicina. Nuestros objetivos fueron evaluar la utilidad de la biopsia usada para realizar el test rápido de ureasa en la detección de resistencia a claritromicina por PCR-RFLP y conocer la distribución de las mutaciones puntuales A2142G y A2143G en el gen ARNr 23S, en relación con los factores de virulencia en nuestra región. Se recolectaron muestras gástricas (n=141) provenientes de pacientes adultos dispépticos y se investigó la presencia de H. pylori mediante el test rápido de ureasa, análisis histopatológico y PCR para el gen hsp60. La resistencia a claritromicina se analizó por PCR-RFLP en 62 muestras pareadas de biopsias gástricas H. pylori+ destinadas al análisis molecular y al test rápido de ureasa. Los factores de virulencia de H. pylori fueron analizados mediante PCR multiplex usando oligonucleótidos específicos para los genes cagA, vacA y babA2. Trece de 62 cepas (20,9%) fueron resistentes a claritromicina, 6/13 (46,2%) llevaron la mutación A2143G, mientras que 7/13 (53,8%) presentaron la mutación A2142G. El genotipo vacA s1m1 fue el más frecuente entre las cepas resistentes a claritromicina. En conclusión, las biopsias destinadas al test rápido de ureasa fueron muestras apropiadas para la detección de la resistencia a claritromicina en pacientes infectados con H. pylori. Esto es especialmente útil en aquellos casos en los que el número o el tamaño de las muestras son limitados. Además, este es el primer reporte de estudio de resistencia a claritromicina (mediante técnicas moleculares), directamente de biopsias gástricas en nuestra región.

Primary antibiotic resistance and its relationship with cagA and vacA genes in Helicobacter pylori isolates from Algerian patients

Abstract The epidemiology of Helicobacter pylori resistance to antibiotics is poorly documented in Africa and especially in Algeria. The aim of our study was to determine the antibiotic resistance rates, as well as its possible relationship with VacA and CagA virulence markers of isolates from Algerian patients. One hundred and fifty one H. pylori isolate were obtained between 2012 and 2015 from 200 patients with upper abdominal pain. Antimicrobial susceptibility testing was performed for amoxicillin, clarithromycin, metronidazole, ciprofloxacin, rifampicin and tetracycline. Molecular identification of H. pylori and the detection of vacA and cagA genes were performed using specific primers. We found that H. pylori was present in 83.5% of collected biopsies, 54.9% of the samples were cagA positive, 49.67% were vacA s1m1, 18.30% were vacA s1m2 and 25.49% were vacA s2m2. Isolates were characterized by no resistance to amoxicillin (0%), tetracycline (0%), rifampicin (0%), a high rate of resistance to metronidazole (61.1%) and a lower rate of resistance to clarithromycin (22.8%) and ciprofloxacin (16.8%). No statically significant relationship was found between vagA and cagA genotypes and antibiotic resistance results (p > 0.5) except for the metronidazole, which had relation with the presence of cagA genotype (p = 0.001).

Helicobacter pylori eradication: influence of interleukin-1beta -31 C/T polymorphism

ABSTRACT Aim To analyze the influence of the -31 C/T polymorphism of the interleukin-1β gene on Helicobacter pylori eradication therapy success in patients with functional dyspepsia. Methods Functional dyspepsia was diagnosed according to the Rome III criteria. All patients underwent upper gastrointestinal endoscopy, and gastric biopsies were obtained at screening and 12 months after randomization (last follow-up visit). Urease test and histological examination were performed to define the H. pylori status. Patients received twice-daily amoxicillin, clarithromycin and omeprazole for 10 days. Genotyping of the interleukin-1beta -31 C/T polymorphism (rs1143627) was performed using polymerase chain reaction-restriction fragment length polymorphism. Results One hundred forty-nine patients received treatment with triple therapy for H. pylori eradication. Only one patient was lost to follow-up, and adherence to study medication was 94.6%. A total of 148 patients (mean age 46.08 ± 12.24 years; 81.8% women) were evaluated for the influence of the interleukin-1beta -31 C/T polymorphism on the outcome of H. pylori eradication therapy. After treatment, bacteria were eradicated in 87% of patients (129/148). Genotype frequencies of the polymorphism were as follows: CC, 38/148 (25.7%); CT, 71/148 (47.9%); and TT, 39/148 (26.4%). Successful eradication rate was 78.9%, 94.4% and 82.1% for the CC, CT and TT genotypes, respectively. The CT genotype was significantly associated with successful H. pylori eradication (p= 0.039). Conclusion This study suggests that the CT genotype of the interleukin-1beta -31 C/T polymorphism plays a role in the successful eradication of H. pylori among patients with functional dyspepsia.

Erradicación de Helicobacter pylori con terapia triple estándar de primera línea / Helicobacter pylori eradication with standard first-line triple therapy

La infección por Helicobacter pylori es una de las infecciones crónicas más comunes a nivel mundial y causa importante de enfermedad péptica y cáncer gástrico. Infecta al 50% de la población adulta con mayor prevalencia en América Central/Sur y Asia y al menos dos veces mayor en poblaciones con alta incidencia de cáncer gástrico. Los objetivos de esta investigación fueron identificar la tasa de erradicación de H. pylori con terapia triple estándar y las posibles características asociadas a su erradicación. Se estudió a 119 pacientes con diagnóstico de infección por H. pylori, seleccionados en forma consecutiva de la consulta externa de Gastroenterología del Hospital General San Juan de Dios. Se realizó endoscopia diagnóstica y toma de biopsia gástrica. Se dio terapia triple estándar con lansoprazol, amoxicilina y claritromicina durante 10 días, seguido de 30 días con lansoprazol. Seis semanas después de completado el tratamiento se evaluó el antígeno de H. pylori en heces para determinar si hubo erradicación. La edad promedio de los participantes fue 49.0 años, 81.5% mujeres, 85.7% de área urbana, el síntoma más común fue dispepsia en 86.6%. En el examen post tratamiento el 89.9%, IC 95% [83.0, 94.7] presentó antígeno en heces negativo. No se encontró asociación entre las características de los pacientes con la respuesta al tratamiento. En conclusión, la respuesta a la terapia triple de primera línea se encuentra dentro del rango aceptable para continuar con ese esquema, pero debe mantenerse una evaluación constante por la presencia de posible resistencia.

Infection by Helicobacter pylori is one of the most common chronic infections worldwide and an important cause of peptic disease and gastric cancer. It infects 50% of the adult population with the highest prevalence in Central / South America and Asia and at least twice as high in populations with a high incidence of gastric cancer. The objectives of this research were to identify the eradication rate of H. pylori after first line standard triple therapy and the possible characteristics associated with its eradication. It was studied 119 patients with a diagnosis of H. pylori infection, selected consecutively from the outpatient department of Gastroenterology of the San Juan de Dios General Hospital. Diagnostic endoscopy and gastric biopsy was performed. Standard triple therapy was given with lansoprazole, amoxicillin and clarithromycin for 10 days, followed by 30 days with lansoprazole. Six weeks after the treatment was completed, the H. pylori antigen in feces was evaluated to determine if there was eradication. The average age of the participants was 49.0 years, 81.5% women, 85.7% of urban area, the most common symptom was dyspepsia in 86.6%. In the post-treatment examination 89.9%, 95% CI [83.0, 94.7] presented negative antigen in feces. No association was found between the characteristics of the patients with the response to treatment. In conclusion, the response to first line triple therapy is within the acceptable range to continue with this scheme, but a constant evaluation must be maintained due to the presence of possible resistance.