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Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City

BACKGROUND: Drug resistance tuberculosis, specially MDR and XDR are a big challenge for diagnosis and treatment. In Mexico the prevalence of MDR is between 3–5%, a number probably underestimated due to lack of diagnostic tests for susceptibility. The National Institute of Respiratory Diseases in Mex...

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Autores principales: Martinez-Orozco, Jose Arturo, Nuñez-Luna, Blanca A, Narváez-Diaz, Luis A, Pilar, Mariela Segura-Del, Mujica-Sanchez, Mario, Salazar-Lezama, Miguel Angel, Mireles-Davalos, Christian D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630868/
http://dx.doi.org/10.1093/ofid/ofx163.1645
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author Martinez-Orozco, Jose Arturo
Nuñez-Luna, Blanca A
Narváez-Diaz, Luis A
Pilar, Mariela Segura-Del
Mujica-Sanchez, Mario
Salazar-Lezama, Miguel Angel
Mireles-Davalos, Christian D
author_facet Martinez-Orozco, Jose Arturo
Nuñez-Luna, Blanca A
Narváez-Diaz, Luis A
Pilar, Mariela Segura-Del
Mujica-Sanchez, Mario
Salazar-Lezama, Miguel Angel
Mireles-Davalos, Christian D
author_sort Martinez-Orozco, Jose Arturo
collection PubMed
description BACKGROUND: Drug resistance tuberculosis, specially MDR and XDR are a big challenge for diagnosis and treatment. In Mexico the prevalence of MDR is between 3–5%, a number probably underestimated due to lack of diagnostic tests for susceptibility. The National Institute of Respiratory Diseases in Mexico City is the national referral center for MDR/XDR tuberculosis. In our country there is no data about the gene mutations involved in drug resistance to first line antituberculosis treatment nor the clinical characteristics that accompany these findings. Objective: Evaluate the prevalence of genotyping profiles according to a line probe assay (LPA) in patients with drug resistance tuberculosis and their associated clinical characteristics METHODS: Retrospective cohort from 2010 to 2014 of M. tuberculosis isolates with any type of resistance to first line antituberculosis drugs identified by MGIT SIRE and in which GenoType MTBDRplus/sl were performed, we evaluate prevalence of genotyping profiles according to the LPA within the isolates and gather data from those with complete medical records to asses clinical characteristics. RESULTS: In 52 and 33 isolates phenotyping and genotyping MTBDRplus/sl respectively were performed, 41 resistant to Isoniazid INH with 75% genotypic concordance, 33 resistant to rifampicin RIF with 75.6% concordance, 14 to streptomycin SM with 23% concordance and 10 to ethambutol EMB with 100% concordance, 54% MDR tuberculosis. The genotyping profile for RIF was absence of probes rpoB Wild Type 8 (WT) 57.7%, WT 7 30.8% and presence of rpoB mutation 3 (MUT) 19.2%. For INH absence of InhA WT2 48.1% and InhA WT1 19.2%. For EMB absence of embB WT1 30.8% and for SM absence of rrs WT1 (19%). Absence of InhA WT1 was associated with female (P = 0.01) and DM2 (P = 0.032) patients, other clinical/biochemical characteristics and mortality was not different in patients with o without the genotypic profile for each drug. Cavitary disease by CT was more frequent in patients with WT probe absence in RIF and INH than those who did not have a LPA suggestive of resistance for this drugs. CONCLUSION: Wild Type probe absense is the frequent finding in our isolates according to LPA in RIF, INH, EMB and SM, intrisic host factors and clinical characteristics seem not to be related to a particular resistant gene profile. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-56308682017-11-07 Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City Martinez-Orozco, Jose Arturo Nuñez-Luna, Blanca A Narváez-Diaz, Luis A Pilar, Mariela Segura-Del Mujica-Sanchez, Mario Salazar-Lezama, Miguel Angel Mireles-Davalos, Christian D Open Forum Infect Dis Abstracts BACKGROUND: Drug resistance tuberculosis, specially MDR and XDR are a big challenge for diagnosis and treatment. In Mexico the prevalence of MDR is between 3–5%, a number probably underestimated due to lack of diagnostic tests for susceptibility. The National Institute of Respiratory Diseases in Mexico City is the national referral center for MDR/XDR tuberculosis. In our country there is no data about the gene mutations involved in drug resistance to first line antituberculosis treatment nor the clinical characteristics that accompany these findings. Objective: Evaluate the prevalence of genotyping profiles according to a line probe assay (LPA) in patients with drug resistance tuberculosis and their associated clinical characteristics METHODS: Retrospective cohort from 2010 to 2014 of M. tuberculosis isolates with any type of resistance to first line antituberculosis drugs identified by MGIT SIRE and in which GenoType MTBDRplus/sl were performed, we evaluate prevalence of genotyping profiles according to the LPA within the isolates and gather data from those with complete medical records to asses clinical characteristics. RESULTS: In 52 and 33 isolates phenotyping and genotyping MTBDRplus/sl respectively were performed, 41 resistant to Isoniazid INH with 75% genotypic concordance, 33 resistant to rifampicin RIF with 75.6% concordance, 14 to streptomycin SM with 23% concordance and 10 to ethambutol EMB with 100% concordance, 54% MDR tuberculosis. The genotyping profile for RIF was absence of probes rpoB Wild Type 8 (WT) 57.7%, WT 7 30.8% and presence of rpoB mutation 3 (MUT) 19.2%. For INH absence of InhA WT2 48.1% and InhA WT1 19.2%. For EMB absence of embB WT1 30.8% and for SM absence of rrs WT1 (19%). Absence of InhA WT1 was associated with female (P = 0.01) and DM2 (P = 0.032) patients, other clinical/biochemical characteristics and mortality was not different in patients with o without the genotypic profile for each drug. Cavitary disease by CT was more frequent in patients with WT probe absence in RIF and INH than those who did not have a LPA suggestive of resistance for this drugs. CONCLUSION: Wild Type probe absense is the frequent finding in our isolates according to LPA in RIF, INH, EMB and SM, intrisic host factors and clinical characteristics seem not to be related to a particular resistant gene profile. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2017-10-04 /pmc/articles/PMC5630868/ http://dx.doi.org/10.1093/ofid/ofx163.1645 Text en © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Martinez-Orozco, Jose Arturo
Nuñez-Luna, Blanca A
Narváez-Diaz, Luis A
Pilar, Mariela Segura-Del
Mujica-Sanchez, Mario
Salazar-Lezama, Miguel Angel
Mireles-Davalos, Christian D
Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City
title Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City
title_full Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City
title_fullStr Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City
title_full_unstemmed Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City
title_short Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City
title_sort prevalence of gene mutations profiles by genotype mtbdrplus/sl to first line antituberculosis drugs and clinical characteristics in drug resistant tuberculosis patients referred to the national institute of respiratory diseases in mexico city
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630868/
http://dx.doi.org/10.1093/ofid/ofx163.1645
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