Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia
ilustraciones, diagramas
- Autores:
-
Hernández Páez, Alexandra
- Tipo de recurso:
- Fecha de publicación:
- 2023
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/84398
- Palabra clave:
- Klebsiella pneumoniae
Aislamiento de Pacientes
Resistencia antimicrobiana
Carbapenemasas
Clones
Secuenciación de genoma completo
Infecciones intrahospitalarias
COVID-19
Antimicrobial resistance
Carbapenemases
Clusters
Nosocomial infections
Whole genome sequencing
Klebsiella pneumoniae
- Rights
- openAccess
- License
- Atribución-NoComercial 4.0 Internacional
id |
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oai_identifier_str |
oai:repositorio.unal.edu.co:unal/84398 |
network_acronym_str |
UNACIONAL2 |
network_name_str |
Universidad Nacional de Colombia |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia |
dc.title.translated.eng.fl_str_mv |
Comparative genomic analysis of clinical isolates of Carbapenemase-producing Klebsiella pneumoniae in patients with and without SARS-CoV2 in the city of Bogotá during the pandemic period |
title |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia |
spellingShingle |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia Klebsiella pneumoniae Aislamiento de Pacientes Resistencia antimicrobiana Carbapenemasas Clones Secuenciación de genoma completo Infecciones intrahospitalarias COVID-19 Antimicrobial resistance Carbapenemases Clusters Nosocomial infections Whole genome sequencing Klebsiella pneumoniae |
title_short |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia |
title_full |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia |
title_fullStr |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia |
title_full_unstemmed |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia |
title_sort |
Análisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemia |
dc.creator.fl_str_mv |
Hernández Páez, Alexandra |
dc.contributor.advisor.none.fl_str_mv |
Barreto Hernández, Emiliano Leal Castro, Aura Lucía |
dc.contributor.author.none.fl_str_mv |
Hernández Páez, Alexandra |
dc.contributor.researchgroup.spa.fl_str_mv |
Bioinformática Epidemiología molecular |
dc.subject.decs.other.fl_str_mv |
Klebsiella pneumoniae |
topic |
Klebsiella pneumoniae Aislamiento de Pacientes Resistencia antimicrobiana Carbapenemasas Clones Secuenciación de genoma completo Infecciones intrahospitalarias COVID-19 Antimicrobial resistance Carbapenemases Clusters Nosocomial infections Whole genome sequencing Klebsiella pneumoniae |
dc.subject.decs.spa.fl_str_mv |
Aislamiento de Pacientes |
dc.subject.proposal.spa.fl_str_mv |
Resistencia antimicrobiana Carbapenemasas Clones Secuenciación de genoma completo Infecciones intrahospitalarias |
dc.subject.proposal.eng.fl_str_mv |
COVID-19 Antimicrobial resistance Carbapenemases Clusters Nosocomial infections Whole genome sequencing |
dc.subject.proposal.other.fl_str_mv |
Klebsiella pneumoniae |
description |
ilustraciones, diagramas |
publishDate |
2023 |
dc.date.accessioned.none.fl_str_mv |
2023-08-01T18:05:42Z |
dc.date.available.none.fl_str_mv |
2023-08-01T18:05:42Z |
dc.date.issued.none.fl_str_mv |
2023-01-31 |
dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/TM |
status_str |
acceptedVersion |
dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/84398 |
dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
url |
https://repositorio.unal.edu.co/handle/unal/84398 https://repositorio.unal.edu.co/ |
identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
dc.language.iso.spa.fl_str_mv |
spa |
language |
spa |
dc.relation.references.spa.fl_str_mv |
Adler, A., Hussein, O., Ben-david, D., Masarwa, S., Navon-venezia, S., Schwaber, M. J., Carmeli, Y., Setton, E., Golan, S., Brill, S., Lipkin, V., Frodin, E., Mendelson, G., Rave, R., Yehuda, N., Aizen, I., Kaganski, M., Gershkovich, P., Sasson, A., … Charish, L. (2015). Persistence of Klebsiella pneumoniae ST258 as the predominant clone of carbapenemase-producing Enterobacteriaceae in post-acute-care hospitals in Israel, 2008-13. Journal of Antimicrobial Chemotherapy, 70(1), 89–92. https://doi.org/10.1093/jac/dku33 Alcock, B. P., Raphenya, A. R., Lau, T. T. Y., Tsang, K. K., Bouchard, M., Edalatmand, A., Huynh, W., Nguyen, A. L. V., Cheng, A. A., Liu, S., Min, S. Y., Miroshnichenko, A., Tran, H. K., Werfalli, R. E., Nasir, J. A., Oloni, M., Speicher, D. J., Florescu, A., Singh, B., … McArthur, A. G. (2020). CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Research, 48(D1), D517–D525. https://doi.org/10.1093/nar/gkz935 Amarsy, R., Jacquier, H., Munier, A. L., Merimèche, M., Berçot, B., & Mégarbane, B. (2021). Outbreak of NDM-1-producing Klebsiella pneumoniae in the intensive care unit during the COVID-19 pandemic: Another nightmare. American Journal of Infection Control, 49(10), 1324–1326. https://doi.org/10.1016/j.ajic.2021.07.004 Andrews, S. (2013). FastQC A Quality Control tool for High Throughput Sequence Data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/ Arabaghian, H., Salloum, T., Alousi, S., Panossian, B., Araj, G. F., & Tokajian, S. (2019). Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae Isolated from Lebanon. Scientific Reports, 9(1). https://doi.org/10.1038/S41598-018-36554-2 Arcari, G., Raponi, G., Sacco, F., Bibbolino, G., Di Lella, F. M., Alessandri, F., Coletti, M., Trancassini, M., Deales, A., Pugliese, F., Antonelli, G., & Carattoli, A. (2021). Klebsiella pneumoniae infections in COVID-19 patients: a 2-month retrospective analysis in an Italian hospital. International Journal of Antimicrobial Agents, 57(1), 106245. https://doi.org/10.1016/j.ijantimicag.2020.106245 Arteaga-Livias, K., Pinzas-Acosta, K., Perez-Abad, L., Panduro-Correa, V., Rabaan, A. A., Pecho-Silva, S., & Dámaso-Mata, B. (2022). A multidrug-resistant Klebsiella pneumoniae outbreak in a Peruvian hospital: Another threat from the COVID-19 pandemic. Infection Control and Hospital Epidemiology, 43(2), 267–268. https://doi.org/10.1017/ice.2020.1401 Bankevich, A., Nurk, S., Antipov, D., Gurevich, A. A., Dvorkin, M., Kulikov, A. S., Lesin, V. M., Nikolenko, S. I., Pham, S., Prjibelski, A. D., Pyshkin, A. V., Sirotkin, A. V., Vyahhi, N., Tesler, G., Alekseyev, M. A., & Pevzner, P. A. (2012). SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. Journal of Computational Biology, 19(5), 455–477. https://doi.org/10.1089/cmb.2012.0021 Bioptic. (2020). Qsep100. https://www.bioptic.com.tw/product/instruments/qsep100- series/qsep100 Bolger, A. M., Lohse, M., & Usadel, B. (2014). Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 30(15), 2114–2120. https://doi.org/10.1093/bioinformatics/btu170 Bush, K., & Jacoby, G. A. (2010). Updated functional classification of β-lactamases. Antimicrobial Agents and Chemotherapy, 54(3), 969–976. https://doi.org/10.1128/AAC.01009-09 Cantón, R., Gijón, D., & Ruiz-Garbajosa, P. (2020). Antimicrobial resistance in ICUs: An update in the light of the COVID-19 pandemic. Current Opinion in Critical Care, 26(5), 433–441. https://doi.org/10.1097/MCC.0000000000000755 Cataño-Correa, J. C., Cardona-Arias, J. A., Mancilla, J. P. P., & García, M. T. (2021). Bacterial superinfection in adults with COVID-19 hospitalized in two clinics in Medellín-Colombia, 2020. PLoS ONE, 16(7 July), 1–12. https://doi.org/10.1371/journal.pone.0254671 CDC. (2019). Antibiotic Resistance Threats in the United States. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf CLSI. (2020). M100-S30: Performance Standards for Antimicrobial Susceptibility Testing; 30th ed. Informational Supplement. https://www.nih.org.pk/wp content/uploads/2021/02/CLSI-2020.pdf Curiao, T., Marchi, E., Viti, C., Oggioni, M. R., Baquero, F., Martinez, J. L., & Coque, T. M. (2015). Polymorphic variation in susceptibility and metabolism of triclosan-resistant mutants of Escherichia coli and Klebsiella pneumoniae clinical strains obtained after exposure to biocides and antibiotics. Antimicrobial Agents and Chemotherapy, 59(6), 3413–3423. https://doi.org/10.1128/AAC.00187-15 De Angelis, G., Giacomo, P. Del, Posteraro, B., Sanguinetti, M., & Tumbarello, M. (2020). Molecular mechanisms, epidemiology, and clinical importance of β-lactam resistance in enterobacteriaceae. In International Journal of Molecular Sciences (Vol. 21, Issue 14, pp. 1–22). MDPI AG. https://doi.org/10.3390/ijms21145090 Dhanoa, A., Fang, N. C., Hassan, S. S., Kaniappan, P., & Rajasekaram, G. (2011). Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: The effects of bacterial coinfection. Virology Journal, 8(1), 501. https://doi.org/10.1186/1743-422X-8-501 Dong, N., Zhang, R., Liu, L., Li, R., Lin, D., Chan, E. W. C., & Chen, S. (2018). Genome analysis of clinical multilocus sequence Type 11 Klebsiella Pneumoniae from China. Microbial Genomics, 4(2). https://doi.org/10.1099/mgen.0.000149 Dortet, L., Girlich, D., Virlouvet, A. L., Poirel, L., Nordmann, P., Iorga, B. I., & Naas, T. (2017). Characterization of BRPMBL, the bleomycin resistance protein associated with the carbapenemase NDM. Antimicrobial Agents and Chemotherapy, 61(3). https://doi.org/10.1128/AAC.02413-16 ECDC. (2018). Vigilancia de Resistencia Antimicrobiana en Europa. https://www.ecdc.europa.eu/sites/default/files/documents/surveillance-antimicrobial resistance-Europe-2018.pdf Founou, R. C., Founou, L. L., Allam, M., Ismail, A., & Essack, S. Y. (2019). Whole Genome Sequencing of Extended Spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae Isolated from Hospitalized Patients in KwaZulu-Natal, South Africa. Scientific Reports, 9(1), 1–11. https://doi.org/10.1038/s41598-019-42672-2 García-Betancur, J. C., Appel, T. M., Esparza, G., Gales, A. C., Levy-Hara, G., Cornistein, W., Vega, S., Nuñez, D., Cuellar, L., Bavestrello, L., Castañeda-Méndez, P. F., Villalobos-Vindas, J. M., & Villegas, M. V. (2021). Update on the epidemiology of carbapenemases in Latin America and the Caribbean. Expert Review of Anti Infective Therapy, 19(2), 197–213. https://doi.org/10.1080/14787210.2020.1813023 García-Meniño, I., Forcelledo, L., Rosete, Y., García-Prieto, E., Escudero, D., & Fernández, J. (2021). Spread of OXA-48-producing Klebsiella pneumoniae among COVID-19-infected patients: The storm after the storm. Journal of Infection and Public Health, 14(1), 50–52. https://doi.org/10.1016/j.jiph.2020.11.001 Ghosh, S., Bornman, C., & Zafer, M. M. (2021). Antimicrobial Resistance Threats in the emerging COVID-19 pandemic: Where do we stand? Journal of Infection and Public Health, 14(5), 555–560. https://doi.org/10.1016/j.jiph.2021.02.011 Gomez-Simmonds, A., Annavajhala, M. K., McConville, T. H., Dietz, D. E., Shoucri, S. M., Laracy, J. C., Rozenberg, F. D., Nelson, B., Greendyke, W. G., Furuya, E. Y., Whittier, S., & Uhlemann, A.-C. (2020). Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital. Journal of Antimicrobial Chemotherapy, November 2020, 380–384. https://doi.org/10.1093/jac/dkaa466 Guo, Y. R., Cao, Q. D., Hong, Z. S., Tan, Y. Y., Chen, S. D., Jin, H. J., Tan, K. Sen, Wang, D. Y., & Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak- A n update on the status. Military Medical Research, 7(1), 1–10. https://doi.org/10.1186/s40779-020-00240-0 Gurevich, A., Saveliev, V., Vyahhi, N., & Tesler, G. (2013). QUAST: Quality assessment tool for genome assemblies. Bioinformatics, 29(8), 1072–1075. https://doi.org/10.1093/bioinformatics/btt086 Hernández, M., Quijada, N. M., Rodríguez-Lázaro, D., & Eiros, J. M. (2020). Bioinformatics of next generation sequencing in clinical microbiology diagnosis. Revista Argentina de Microbiologia, 52(2), 150–161. https://doi.org/10.1016/j.ram.2019.06.003 Holt, K. E., Wertheim, H., Zadoks, R. N., Baker, S., Whitehouse, C. A., Dance, D., Jenney, A., Connor, T. R., Hsu, L. Y., Severin, J., Brisse, S., Cao, H., Wilksch, J., Gorrie, C., Schultz, M. B., Edwards, D. J., Van Nguyen, K., Nguyen, T. V., Dao, T. T., … Thomson, N. R. (2015). Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proceedings of the National Academy of Sciences of the United States of America, 112(27), E3574–E3581. https://doi.org/10.1073/pnas.1501049112 Hoque, M. N., Akter, S., Mishu, I. D., Islam, M. R., Rahman, M. S., Akhter, M., Islam, I., Hasan, M. M., Rahaman, M. M., Sultana, M., Islam, T., & Hossain, M. A. (2021). Microbial co-infections in COVID-19: Associated microbiota and underlying mechanisms of pathogenesis. Microbial Pathogenesis, 156(April), 104941. https://doi.org/10.1016/j.micpath.2021.104941 Howard-Jones, A. R., Sandaradura, I., Robinson, R., Orde, S. R., Iredell, J., Ginn, A., van Hal, S., & Branley, J. (2022). Multidrug-resistant OXA-48/CTX-M-15 Klebsiella pneumoniae cluster in a COVID-19 intensive care unit: salient lessons for infection prevention and control during the COVID-19 pandemic. Journal of Hospital Infection, 126, 64–69. https://doi.org/10.1016/j.jhin.2022.05.001 Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5 Illumina. (2020). Illumina DNA Prep Reference Guide. www.illumina.com/company/legal.html.%0Ahttps://support.illumina.com/content/dam/ illumina-support/documents/documentation/chemistry_documentation/illumina_prep/illumina- dna-prep-reference-guide-1000000025416-09.pdf INS. (2019). Informe de Resultados de la Vigilancia por Laboratorio de Resistencia Antimicrobiana en Infecciones Asociadas a La Atención en Salud (IAAS) 2018. https://www.ins.gov.co/buscador-eventos/Informacin de laboratorio/Informe vigilancia-por-laboratorio-resistencia-antimicrobiana-y-whonet-IAAS-2018.pdf Instituto Nacional de Salud [INS]. (2022). COVID-19 en Colombia. https://www.ins.gov.co/Noticias/Paginas/Coronavirus.aspx Invitrogen. (2020). PureLink® Genomic DNA Kits. https://assets.thermofisher.com/TFS Assets/LSG/ manuals/purelink_genomic_man.pdf Kieffer, N., Aires-de-Sousa, M., Nordmann, P., & Poirel, L. (2017). High rate of MCR-1– producing Escherichia coli and Klebsiella pneumoniae among pigs, Portugal. Emerging Infectious Diseases, 23(12), 2023–2029. https://doi.org/10.3201/eid2312.170883 Krapp, F., Morris, A. R., Ozer, E. A., & Hauser, A. R. (2017). Virulence Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Strains from Patients with Necrotizing Skin and Soft Tissue Infections. Scientific Reports, 7(1), 1–14. https://doi.org/10.1038/s41598-017-13524-8 Lee, Y. J., Huang, C. H., Ilsan, N. A., Lee, I. H., & Huang, T. W. (2021). Molecular epidemiology and characterization of carbapenem-resistant klebsiella pneumoniae isolated from urine at a teaching hospital in Taiwan. Microorganisms, 9(2), 1–15. https://doi.org/10.3390/microorganisms9020271 Letunic, I., & Bork, P. (2021). Interactive tree of life (iTOL) v5: An online tool for phylogenetic tree display and annotation. Nucleic Acids Research, 49(W1), W293– W296. https://doi.org/10.1093/nar/gkab301 Li, J., Zhang, H., Ning, J., Sajid, A., Cheng, G., Yuan, Z., & Hao, H. (2019). The nature and epidemiology of OqxAB, a multidrug efflux pump. Antimicrobial Resistance and Infection Control, 8(1), 1–13. https://doi.org/10.1186/s13756-019-0489-3 Lomonaco, S., Crawford, M. A., Lascols, C., Timme, R. E., Anderson, K., Hodge, D. R., Fisher, D. J., Pillai, S. P., Morse, S. A., Khan, E., Hughes, M. A., Allard, M. W., & Sharma, S. K. (2018). Resistome of carbapenem- and colistin-resistant Klebsiella pneumoniae clinical isolates. PLoS ONE, 13(6), 1–23. https://doi.org/10.1371/journal.pone.0198526 Manohar, P., Loh, B., Nachimuthu, R., Hua, X., Welburn, S. C., & Leptihn, S. (2020). Secondary Bacterial Infections in Patients With Viral Pneumonia. Frontiers in Medicine, 7(August), 2013–2016. https://doi.org/10.3389/fmed.2020.00420 Martin, R. M., & Bachman, M. A. (2018). Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology, 8(JAN), 1–15. https://doi.org/10.3389/fcimb.2018.00004 Mędrzycka-Dabrowska, W., Lange, S., Zorena, K., Dabrowski, S., Ozga, D., & Tomaszek, L. (2021). Carbapenem-resistant klebsiella pneumoniae infections in icu covid-19 patients—a scoping review. Journal of Clinical Medicine, 10(10), 1–13. https://doi.org/10.3390/jcm10102067 Meir-Gruber, L., Manor, Y., Gefen-Halevi, S., Hindiyeh, M. Y., Mileguir, F., Azar, R., Smollan, G., Belausov, N., Rahav, G., Shamiss, A., Mendelson, E., & Keller, N. (2016). Population screening using sewage reveals pan-resistant bacteria in hospital and community samples. PLoS ONE, 11(10), 1–13. https://doi.org/10.1371/journal.pone.0164873 Mendes, G., Ramalho, J. F., Duarte, A., Pedrosa, A., Silva, A. C., Méndez, L., & Caneiras, C. (2022). First Outbreak of NDM-1-Producing Klebsiella pneumoniae ST11 in a Portuguese Hospital Centre during the COVID-19 Pandemic. Microorganisms, 10(2), 1–14. https://doi.org/10.3390/microorganisms10020251 Navon-Venezia, S., Kondratyeva, K., & Carattoli, A. (2017). Klebsiella pneumoniae: A major worldwide source and shuttle for antibiotic resistance. FEMS Microbiology Reviews, 41(3), 252–275. https://doi.org/10.1093/femsre/fux013 Nori, P., Cowman, K., Chen, V., Bartash, R., Szymczak, W., Madaline, T., Punjabi Katiyar, C., Jain, R., Aldrich, M., Weston, G., Gialanella, P., Corpuz, M., Gendlina, I., & Guo, Y. (2020). Bacterial and fungal co-infections in COVID-19 patients hospitalized during the New York city pandemic surge. Infection Control and Hospital Epidemiology, 2020, 1–5. https://doi.org/10.1017/ice.2020.368 OECD. (2018). Stemming the Superbug Tide: Just A Few Dollars More. https://www.oecd.org/els/health-systems/Stemming-the-Superbug-Tide-Policy-Brief 2018.pdf OMS. (2017). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb ET_NM_WHO.pdf?ua=1 Organización Mundial de la Salud [OMS]. (2022). Panel de la OMS sobre la enfermedad por coronavirus (COVID-19). https://covid19.who.int/ Österblad, M., Kirveskari, J., Hakanen, A. J., Tissari, P., Vaara, M., & Jalava, J. (2012). Carbapenemase-producing enterobacteriaceae in Finland: The first years (2008-11). Journal of Antimicrobial Chemotherapy, 67(12), 2860–2864. https://doi.org/10.1093/jac/dks299 Pintado, V., Ruiz-Garbajosa, P., Escudero-Sanchez, R., Gioia, F., Herrera, S., Vizcarra, P., Fortún, J., Cobo, J., Martín-Dávila, P., Morosini, M. I., Cantón, R., & Moreno, S. (2022). Carbapenemase-producing Enterobacterales infections in COVID-19 patients. Infectious Diseases, 54(1), 36–45. https://doi.org/10.1080/23744235.2021.1963471 Pitout, J. D. D., Nordmann, P., & Poirel, L. (2015). Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. In Antimicrobial Agents and Chemotherapy (Vol. 59, Issue 10, pp. 5873–5884). American Society for Microbiology. https://doi.org/10.1128/AAC.01019-15 Prezioso, S. M., Brown, N. E., & Goldberg, J. B. (2017). Elfamycins: inhibitors of elongation factor-Tu. Molecular Microbiology, 106(1), 22–34. https://doi.org/10.1111/mmi.13750 PubMLST. (2022). Bases de datos públicas para tipificación molecular y diversidad del genoma microbiano. https://pubmlst.org/ Pulzova, L., Navratilova, L., & Comor, L. (2017). Alterations in Outer Membrane Permeability Favor Drug-Resistant Phenotype of Klebsiella pneumoniae. Microbial Drug Resistance, 23(4), 413–420. https://doi.org/10.1089/mdr.2016.0017 Remolina Granados, S. A., & Escobar Castaño, C. J. (2017). Descripción de Tipos de Carbapenemasas Expresadas en Klebsiella sp. y Pseudomonas aeruginosa en Hospitales de Tercer Nivel de la Ciudad de Bogotá, Estudio Descriptivo. Parte 1 [Tesis de Especialización, Universidad Nacional de Colombia]. https://repositorio.unal.edu.co/bitstream/handle/unal/62824/SergioA.RemolinaGrana dos.2017.pdf?sequence=1&isAllowed=y Rojas, L. J., Weinstock, G. M., De La Cadena, E., Diaz, L., Rios, R., Hanson, B. M., Brown, J. S., Vats, P., Phillips, D. S., Nguyen, H., Hujer, K. M., Correa, A., Adams, M. D., Perez, F., Sodergren, E., Narechania, A., Planet, P. J., Villegas, M. V., Bonomo, R. T. A., & Arias, C. A. (2018). An analysis of the epidemic of klebsiella pneumoniae carbapenemase-producing k. pneumoniae: Convergence of two evolutionary mechanisms creates the “perfect storm.” Journal of Infectious Diseases, 217(1), 82–92. https://doi.org/10.1093/infdis/jix524 Saavedra, S. Y., Bernal, J. F., Montilla-Escudero, E., Arévalo, S. A., Prada, D. A., Valencia, M. F., Moreno, J., Hidalgo, A. M., Garciá-Vega, Á. S., Abrudan, M., Argimón, S., Kekre, M., Underwood, A., Aanensen, D. M., Duarte, C., Donado Godoy, P., Abudahab, K., Harste, H., Muddyman, D., … Vegvari, C. (2021). Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs. Clinical Infectious Diseases, 73(Suppl 4), S290–S299. https://doi.org/10.1093/cid/ciab777 Saini, V., Jain, C., Singh, N. P., Alsulimani, A., Gupta, C., Dar, S. A., Haque, S., & Das, S. (2021). Paradigm shift in antimicrobial resistance pattern of bacterial isolates during the covid-19 pandemic. Antibiotics, 10(8), 1–11. https://doi.org/10.3390/antibiotics10080954 Samanta, I., & Bandyopadhyay, S. (2020). Klebsiella. Antimicrobial Resistance in Agriculture, 258, 153–169. https://doi.org/10.1016/b978-0-12-815770-1.00014-6 Seemann, T. (2014). Prokka: Rapid prokaryotic genome annotation. Bioinformatics, 30(14), 2068–2069. https://doi.org/10.1093/bioinformatics/btu153 Sepandi, M., Taghdir, M., Alimohamadi, Y., Afrashteh, S., & Hosamirudsari, H. (2020). Factors associated with mortality in COVID-19 patients: A systematic review and meta-analysis. Iranian Journal of Public Health, 49(7), 1211–1221. https://doi.org/10.18502/ijph.v49i7.3574 Shelburne, S. A., Kim, J., Munita, J. M., Sahasrabhojane, P., Shields, R. K., Press, E. G., Li, X., Arias, C. A., Cantarel, B., Jiang, Y., Kim, M. S., Aitken, S. L., & Greenberg, D. E. (2017). Whole-genome sequencing accurately identifies resistance to extended spectrum β-lactams for major gram-negative bacterial pathogens. Clinical Infectious Diseases, 65(5), 738–745. https://doi.org/10.1093/cid/cix417 Shelenkov, A., Petrova, L., Mironova, A., Zamyatin, M., Akimkin, V., & Mikhaylova, Y. (2022). Long-Read Whole Genome Sequencing Elucidates the Mechanisms of Amikacin Resistance in Multidrug-Resistant Klebsiella pneumoniae Isolates Obtained from COVID-19 Patients. Antibiotics, 11(10). https://doi.org/10.3390/antibiotics11101364 Shon, A. S., Bajwa, R. P. S., & Russo, T. A. (2013). Hypervirulent (hypermucoviscous) Klebsiella Pneumoniae: A new and dangerous breed. Virulence, 4(2), 107–118. https://doi.org/10.4161/viru.22718 Stamatakis, A. (2014). RAxML version 8: A tool for phylogenetic analysis and post analysis of large phylogenies. Bioinformatics, 30(9), 1312–1313. https://doi.org/10.1093/bioinformatics/btu033 Suárez, C., & Gudiol, F. (2009). Beta-lactam antibiotics. Enfermedades Infecciosas y Microbiologia Clinica, 27(2), 116–129. https://doi.org/10.1016/j.eimc.2008.12.001 Talero Osorio, D. C. (2022). Identificación de contigs asociados a plásmidos obtenidos a partir de secuenciación de genoma completo de aislamientos de Klebsiella pneumoniae. Universidad Nacional de Colombia. [Universidad Nacional de Colombia]. https://repositorio.unal.edu.co/handle/unal/81811 T.Seemann. (2022a). mlst Github. https://github.com/tseemann/mlst T.Seemann. (2022b). snippy. https://github.com/tseemann/snippy Thermo ScientificTM OxoidTM. (2020). Medios deshidratados. http://www.analisisavanzados.com/index.php/catalogo-general-de-productos oxoid?article=&id=119 Tiri, B., Sensi, E., Marsiliani, V., Cantarini, M., Priante, G., Vernelli, C., Martella, L. A., Costantini, M., Mariottini, A., Andreani, P., Bruzzone, P., Suadoni, F., Francucci, M., Cirocchi, R., & Cappanera, S. (2020). Antimicrobial Stewardship Program, COVID 19, and Infection Control: Spread of Carbapenem-Resistant Klebsiella Pneumoniae Colonization in ICU COVID-19 Patients. What Did Not Work? Journal of Clinical Medicine, 9(9), 2744. https://doi.org/10.3390/jcm9092744 Wilson, H., & Török, M. E. (2018). Extended-spectrum β-lactamase-producing and carbapenemase-producing Enterobacteriaceae. Microbial Genomics, 4(7). https://doi.org/10.1099/mgen.0.000197 World Health Organization. (2020). Coronavirus disease 2019 (COVID-19): situation report, 51. World Health Organization. https://apps.who.int/iris/handle/10665/331475 Wu, H., Li, D., Zhou, H., Sun, Y., Guo, ling, & Shen, D. (2017). Bacteremia and other body site infection caused by hypervirulent and classic Klebsiella pneumoniae. Microbial Pathogenesis, 104, 254–262. https://doi.org/10.1016/j.micpath.2017.01.049 Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G. F., & Tan, W. (2020). A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine, 382(8), 727–733. https://doi.org/10.1056/nejmoa2001017 Zhu, X., Ge, Y., Wu, T., Zhao, K., Chen, Y., Wu, B., Zhu, F., Zhu, B., & Cui, L. (2020). Co infection with respiratory pathogens among COVID-2019 cases Xiaojuan. Virus Research, 285. https://doi.org/https://doi.org/10.1016/j.virusres.2020.198005 |
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Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Barreto Hernández, Emilianob7a2cae2c08b5d6a549e173576c6c82d600Leal Castro, Aura Lucíaf07a334eb72fd9cef067a37ca1553060600Hernández Páez, Alexandraa0d33acb109172d55ac392c7f172beb2BioinformáticaEpidemiología molecular2023-08-01T18:05:42Z2023-08-01T18:05:42Z2023-01-31https://repositorio.unal.edu.co/handle/unal/84398Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasDurante la pandemia de COVID-19 se detectaron en los pacientes afectados por SARS-CoV-2 K. pneumoniae resistentes a carbapenémicos, lo que conduce a desenlaces fatales y desafíos para la resistencia antimicrobiana. En nuestro estudio, realizado en un hospital durante un periodo de la pandemia, se obtuvo la comparación epidemiológica y genómica de dos grupos de CRKP: 14 y 25, aisladas respectivamente de 10 y 19 pacientes COVID-19 y sin COVID-19; resaltando que las primeras CRKP fueron más resistentes frente a β-lactámicos como cefoxitina, pero menos resistentes frente a trimetoprim/sulfametoxazol y ciprofloxacina que las segundas CRKP. Fueron detectados 75 genes en todos los aislamientos del estudio; se presentaron coproducciones de genes relacionados con carbapenemasas en algunos de los genomas, la Kp082 tenía: NDM-1, KPC-3, GES-2, OXA-2 una combinación no reportada en K. pneumoniae. Se observó la diversidad genética de los dos grupos de aislamientos del estudio, dada por la presencia de variedad de STs y el árbol filogenético basado en los SNPs del core, donde se evidenció que 43,6% de las CRKP pertenecientes a los dos grupos de estudio presentes en el clado IV se asignaron a ST1082. Además, reveló que los pacientes 7, 19 y 8 presentaban aislamientos distribuidos en diferentes clados y como el resistoma presente en las CRKP aun de un mismo clon era variable. Estos hallazgos resaltan la necesidad de dirigir acciones para mejorar continuamente los protocolos de prevención, control de infecciones y programas de administración de antimicrobianos a fin de frenar la expansión de CRKP. (Texto tomado de la fuente)During the COVID-19 pandemic, carbapenem-resistant K. pneumoniae were detected in SARS-CoV-2-affected patients, leading to fatal outcomes and challenges to antimicrobial resistance. In our study, carried out in a hospital during a period of the pandemic, the epidemiological and genomic comparison of two groups of CRKP was obtained: 14 and 25, isolated respectively from 10 and 19 COVID-19 and non-COVID-19 patients; highlighting that the first CRKPs were more resistant against β-lactams such as cefoxitin, but less resistant against trimethoprim/sulfamethoxazole and ciprofloxacin than the second CRKPs. 75 genes were detected in all the study isolates; co-productions of genes related to carbapenemases were present in some of the genomes, Kp082 had: NDM-1, KPC-3, GES-2, OXA-2, a combination not reported in K. pneumoniae. The genetic diversity of the two groups of isolates in the study was observed, given the presence of a variety of STs and the phylogenetic tree based on the SNPs of the core, where it was evidenced that 43.6% of the CRKPs belonging to the two groups of study present in clade IV were assigned to ST1082. In addition, it revealed that patients 7, 19 and 8 had isolates distributed in different clades and that the resistome present in the CRKP even from the same clone was variable. These findings highlight the need for targeted actions to continually improve infection prevention, control protocols, and antimicrobial stewardship programs to curb the spread of CRKP.MaestríaMagíster en Ciencias - MicrobiologíaEste es un estudio de corte trasversal, a partir del cual se seleccionaron aislamientos de K. pneumoniae resistentes a carbapenémicos (CRKP) de 29 pacientes, los cuales ingresaron entre el 02 de enero del 2020 y el 10 de julio del 2021, en un hospital de tercer nivel de la ciudad de Bogotá D.C. Los pacientes correspondían a dos grupos, un grupo conformado por pacientes que hubieran ingresado al hospital con diagnóstico clínico de COVID-19 y/o con una prueba de PCR o Ag positivo para SARS-CoV-2 o que hubieran desarrollado esta enfermedad de manera intrahospitalaria posterior a su admisión; mientras que el otro grupo comprendía aquellos pacientes negativos para COVID-19 desde el ingreso y hasta la recolección del aislamiento.Biología Molecular de Agentes Infecciososxvii, 81 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - MicrobiologíaFacultad de CienciasBogota, ColombiaUniversidad Nacional de Colombia - Sede BogotáAnálisis genómico comparativo de aislamientos clínicos de Klebsiella pneumoniae productores de carbapenemasas en pacientes con y sin SARS-CoV2 de la ciudad de Bogotá durante el periodo de pandemiaComparative genomic analysis of clinical isolates of Carbapenemase-producing Klebsiella pneumoniae in patients with and without SARS-CoV2 in the city of Bogotá during the pandemic periodTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBogotáAdler, A., Hussein, O., Ben-david, D., Masarwa, S., Navon-venezia, S., Schwaber, M. J., Carmeli, Y., Setton, E., Golan, S., Brill, S., Lipkin, V., Frodin, E., Mendelson, G., Rave, R., Yehuda, N., Aizen, I., Kaganski, M., Gershkovich, P., Sasson, A., … Charish, L. (2015). Persistence of Klebsiella pneumoniae ST258 as the predominant clone of carbapenemase-producing Enterobacteriaceae in post-acute-care hospitals in Israel, 2008-13. Journal of Antimicrobial Chemotherapy, 70(1), 89–92. https://doi.org/10.1093/jac/dku33Alcock, B. P., Raphenya, A. R., Lau, T. T. Y., Tsang, K. K., Bouchard, M., Edalatmand, A., Huynh, W., Nguyen, A. L. V., Cheng, A. A., Liu, S., Min, S. Y., Miroshnichenko, A., Tran, H. K., Werfalli, R. E., Nasir, J. A., Oloni, M., Speicher, D. J., Florescu, A., Singh, B., … McArthur, A. G. (2020). CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Research, 48(D1), D517–D525. https://doi.org/10.1093/nar/gkz935Amarsy, R., Jacquier, H., Munier, A. L., Merimèche, M., Berçot, B., & Mégarbane, B. (2021). Outbreak of NDM-1-producing Klebsiella pneumoniae in the intensive care unit during the COVID-19 pandemic: Another nightmare. American Journal of Infection Control, 49(10), 1324–1326. https://doi.org/10.1016/j.ajic.2021.07.004Andrews, S. (2013). FastQC A Quality Control tool for High Throughput Sequence Data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/Arabaghian, H., Salloum, T., Alousi, S., Panossian, B., Araj, G. F., & Tokajian, S. (2019). Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae Isolated from Lebanon. Scientific Reports, 9(1). https://doi.org/10.1038/S41598-018-36554-2Arcari, G., Raponi, G., Sacco, F., Bibbolino, G., Di Lella, F. M., Alessandri, F., Coletti, M., Trancassini, M., Deales, A., Pugliese, F., Antonelli, G., & Carattoli, A. (2021). Klebsiella pneumoniae infections in COVID-19 patients: a 2-month retrospective analysis in an Italian hospital. International Journal of Antimicrobial Agents, 57(1), 106245. https://doi.org/10.1016/j.ijantimicag.2020.106245Arteaga-Livias, K., Pinzas-Acosta, K., Perez-Abad, L., Panduro-Correa, V., Rabaan, A. A., Pecho-Silva, S., & Dámaso-Mata, B. (2022). A multidrug-resistant Klebsiella pneumoniae outbreak in a Peruvian hospital: Another threat from the COVID-19 pandemic. Infection Control and Hospital Epidemiology, 43(2), 267–268. https://doi.org/10.1017/ice.2020.1401Bankevich, A., Nurk, S., Antipov, D., Gurevich, A. A., Dvorkin, M., Kulikov, A. S., Lesin, V. M., Nikolenko, S. I., Pham, S., Prjibelski, A. D., Pyshkin, A. V., Sirotkin, A. V., Vyahhi, N., Tesler, G., Alekseyev, M. A., & Pevzner, P. A. (2012). SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. Journal of Computational Biology, 19(5), 455–477. https://doi.org/10.1089/cmb.2012.0021Bioptic. (2020). Qsep100. https://www.bioptic.com.tw/product/instruments/qsep100- series/qsep100Bolger, A. M., Lohse, M., & Usadel, B. (2014). Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 30(15), 2114–2120. https://doi.org/10.1093/bioinformatics/btu170Bush, K., & Jacoby, G. A. (2010). Updated functional classification of β-lactamases. Antimicrobial Agents and Chemotherapy, 54(3), 969–976. https://doi.org/10.1128/AAC.01009-09Cantón, R., Gijón, D., & Ruiz-Garbajosa, P. (2020). Antimicrobial resistance in ICUs: An update in the light of the COVID-19 pandemic. Current Opinion in Critical Care, 26(5), 433–441. https://doi.org/10.1097/MCC.0000000000000755Cataño-Correa, J. C., Cardona-Arias, J. A., Mancilla, J. P. P., & García, M. T. (2021). Bacterial superinfection in adults with COVID-19 hospitalized in two clinics in Medellín-Colombia, 2020. PLoS ONE, 16(7 July), 1–12. https://doi.org/10.1371/journal.pone.0254671CDC. (2019). Antibiotic Resistance Threats in the United States. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdfCLSI. (2020). M100-S30: Performance Standards for Antimicrobial Susceptibility Testing; 30th ed. Informational Supplement. https://www.nih.org.pk/wp content/uploads/2021/02/CLSI-2020.pdfCuriao, T., Marchi, E., Viti, C., Oggioni, M. R., Baquero, F., Martinez, J. L., & Coque, T. M. (2015). Polymorphic variation in susceptibility and metabolism of triclosan-resistant mutants of Escherichia coli and Klebsiella pneumoniae clinical strains obtained after exposure to biocides and antibiotics. Antimicrobial Agents and Chemotherapy, 59(6), 3413–3423. https://doi.org/10.1128/AAC.00187-15De Angelis, G., Giacomo, P. Del, Posteraro, B., Sanguinetti, M., & Tumbarello, M. (2020). Molecular mechanisms, epidemiology, and clinical importance of β-lactam resistance in enterobacteriaceae. In International Journal of Molecular Sciences (Vol. 21, Issue 14, pp. 1–22). MDPI AG. https://doi.org/10.3390/ijms21145090Dhanoa, A., Fang, N. C., Hassan, S. S., Kaniappan, P., & Rajasekaram, G. (2011). Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: The effects of bacterial coinfection. Virology Journal, 8(1), 501. https://doi.org/10.1186/1743-422X-8-501Dong, N., Zhang, R., Liu, L., Li, R., Lin, D., Chan, E. W. C., & Chen, S. (2018). Genome analysis of clinical multilocus sequence Type 11 Klebsiella Pneumoniae from China. Microbial Genomics, 4(2). https://doi.org/10.1099/mgen.0.000149Dortet, L., Girlich, D., Virlouvet, A. L., Poirel, L., Nordmann, P., Iorga, B. I., & Naas, T. (2017). Characterization of BRPMBL, the bleomycin resistance protein associated with the carbapenemase NDM. Antimicrobial Agents and Chemotherapy, 61(3). https://doi.org/10.1128/AAC.02413-16ECDC. (2018). Vigilancia de Resistencia Antimicrobiana en Europa. https://www.ecdc.europa.eu/sites/default/files/documents/surveillance-antimicrobial resistance-Europe-2018.pdfFounou, R. C., Founou, L. L., Allam, M., Ismail, A., & Essack, S. Y. (2019). Whole Genome Sequencing of Extended Spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae Isolated from Hospitalized Patients in KwaZulu-Natal, South Africa. Scientific Reports, 9(1), 1–11. https://doi.org/10.1038/s41598-019-42672-2García-Betancur, J. C., Appel, T. M., Esparza, G., Gales, A. C., Levy-Hara, G., Cornistein, W., Vega, S., Nuñez, D., Cuellar, L., Bavestrello, L., Castañeda-Méndez, P. F., Villalobos-Vindas, J. M., & Villegas, M. V. (2021). Update on the epidemiology of carbapenemases in Latin America and the Caribbean. Expert Review of Anti Infective Therapy, 19(2), 197–213. https://doi.org/10.1080/14787210.2020.1813023García-Meniño, I., Forcelledo, L., Rosete, Y., García-Prieto, E., Escudero, D., & Fernández, J. (2021). Spread of OXA-48-producing Klebsiella pneumoniae among COVID-19-infected patients: The storm after the storm. Journal of Infection and Public Health, 14(1), 50–52. https://doi.org/10.1016/j.jiph.2020.11.001Ghosh, S., Bornman, C., & Zafer, M. M. (2021). Antimicrobial Resistance Threats in the emerging COVID-19 pandemic: Where do we stand? Journal of Infection and Public Health, 14(5), 555–560. https://doi.org/10.1016/j.jiph.2021.02.011Gomez-Simmonds, A., Annavajhala, M. K., McConville, T. H., Dietz, D. E., Shoucri, S. M., Laracy, J. C., Rozenberg, F. D., Nelson, B., Greendyke, W. G., Furuya, E. Y., Whittier, S., & Uhlemann, A.-C. (2020). Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital. Journal of Antimicrobial Chemotherapy, November 2020, 380–384. https://doi.org/10.1093/jac/dkaa466Guo, Y. R., Cao, Q. D., Hong, Z. S., Tan, Y. Y., Chen, S. D., Jin, H. J., Tan, K. Sen, Wang, D. Y., & Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak- A n update on the status. Military Medical Research, 7(1), 1–10. https://doi.org/10.1186/s40779-020-00240-0Gurevich, A., Saveliev, V., Vyahhi, N., & Tesler, G. (2013). QUAST: Quality assessment tool for genome assemblies. Bioinformatics, 29(8), 1072–1075. https://doi.org/10.1093/bioinformatics/btt086Hernández, M., Quijada, N. M., Rodríguez-Lázaro, D., & Eiros, J. M. (2020). Bioinformatics of next generation sequencing in clinical microbiology diagnosis. Revista Argentina de Microbiologia, 52(2), 150–161. https://doi.org/10.1016/j.ram.2019.06.003Holt, K. E., Wertheim, H., Zadoks, R. N., Baker, S., Whitehouse, C. A., Dance, D., Jenney, A., Connor, T. R., Hsu, L. Y., Severin, J., Brisse, S., Cao, H., Wilksch, J., Gorrie, C., Schultz, M. B., Edwards, D. J., Van Nguyen, K., Nguyen, T. V., Dao, T. T., … Thomson, N. R. (2015). Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proceedings of the National Academy of Sciences of the United States of America, 112(27), E3574–E3581. https://doi.org/10.1073/pnas.1501049112Hoque, M. N., Akter, S., Mishu, I. D., Islam, M. R., Rahman, M. S., Akhter, M., Islam, I., Hasan, M. M., Rahaman, M. M., Sultana, M., Islam, T., & Hossain, M. A. (2021). Microbial co-infections in COVID-19: Associated microbiota and underlying mechanisms of pathogenesis. Microbial Pathogenesis, 156(April), 104941. https://doi.org/10.1016/j.micpath.2021.104941Howard-Jones, A. R., Sandaradura, I., Robinson, R., Orde, S. R., Iredell, J., Ginn, A., van Hal, S., & Branley, J. (2022). Multidrug-resistant OXA-48/CTX-M-15 Klebsiella pneumoniae cluster in a COVID-19 intensive care unit: salient lessons for infection prevention and control during the COVID-19 pandemic. Journal of Hospital Infection, 126, 64–69. https://doi.org/10.1016/j.jhin.2022.05.001Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5Illumina. (2020). Illumina DNA Prep Reference Guide. www.illumina.com/company/legal.html.%0Ahttps://support.illumina.com/content/dam/ illumina-support/documents/documentation/chemistry_documentation/illumina_prep/illumina- dna-prep-reference-guide-1000000025416-09.pdfINS. (2019). Informe de Resultados de la Vigilancia por Laboratorio de Resistencia Antimicrobiana en Infecciones Asociadas a La Atención en Salud (IAAS) 2018. https://www.ins.gov.co/buscador-eventos/Informacin de laboratorio/Informe vigilancia-por-laboratorio-resistencia-antimicrobiana-y-whonet-IAAS-2018.pdfInstituto Nacional de Salud [INS]. (2022). COVID-19 en Colombia. https://www.ins.gov.co/Noticias/Paginas/Coronavirus.aspxInvitrogen. (2020). PureLink® Genomic DNA Kits. https://assets.thermofisher.com/TFS Assets/LSG/ manuals/purelink_genomic_man.pdfKieffer, N., Aires-de-Sousa, M., Nordmann, P., & Poirel, L. (2017). High rate of MCR-1– producing Escherichia coli and Klebsiella pneumoniae among pigs, Portugal. Emerging Infectious Diseases, 23(12), 2023–2029. https://doi.org/10.3201/eid2312.170883Krapp, F., Morris, A. R., Ozer, E. A., & Hauser, A. R. (2017). Virulence Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Strains from Patients with Necrotizing Skin and Soft Tissue Infections. Scientific Reports, 7(1), 1–14. https://doi.org/10.1038/s41598-017-13524-8Lee, Y. J., Huang, C. H., Ilsan, N. A., Lee, I. H., & Huang, T. W. (2021). Molecular epidemiology and characterization of carbapenem-resistant klebsiella pneumoniae isolated from urine at a teaching hospital in Taiwan. Microorganisms, 9(2), 1–15. https://doi.org/10.3390/microorganisms9020271Letunic, I., & Bork, P. (2021). Interactive tree of life (iTOL) v5: An online tool for phylogenetic tree display and annotation. Nucleic Acids Research, 49(W1), W293– W296. https://doi.org/10.1093/nar/gkab301Li, J., Zhang, H., Ning, J., Sajid, A., Cheng, G., Yuan, Z., & Hao, H. (2019). The nature and epidemiology of OqxAB, a multidrug efflux pump. Antimicrobial Resistance and Infection Control, 8(1), 1–13. https://doi.org/10.1186/s13756-019-0489-3Lomonaco, S., Crawford, M. A., Lascols, C., Timme, R. E., Anderson, K., Hodge, D. R., Fisher, D. J., Pillai, S. P., Morse, S. A., Khan, E., Hughes, M. A., Allard, M. W., & Sharma, S. K. (2018). Resistome of carbapenem- and colistin-resistant Klebsiella pneumoniae clinical isolates. PLoS ONE, 13(6), 1–23. https://doi.org/10.1371/journal.pone.0198526Manohar, P., Loh, B., Nachimuthu, R., Hua, X., Welburn, S. C., & Leptihn, S. (2020). Secondary Bacterial Infections in Patients With Viral Pneumonia. Frontiers in Medicine, 7(August), 2013–2016. https://doi.org/10.3389/fmed.2020.00420Martin, R. M., & Bachman, M. A. (2018). Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology, 8(JAN), 1–15. https://doi.org/10.3389/fcimb.2018.00004Mędrzycka-Dabrowska, W., Lange, S., Zorena, K., Dabrowski, S., Ozga, D., & Tomaszek, L. (2021). Carbapenem-resistant klebsiella pneumoniae infections in icu covid-19 patients—a scoping review. Journal of Clinical Medicine, 10(10), 1–13. https://doi.org/10.3390/jcm10102067Meir-Gruber, L., Manor, Y., Gefen-Halevi, S., Hindiyeh, M. Y., Mileguir, F., Azar, R., Smollan, G., Belausov, N., Rahav, G., Shamiss, A., Mendelson, E., & Keller, N. (2016). Population screening using sewage reveals pan-resistant bacteria in hospital and community samples. PLoS ONE, 11(10), 1–13. https://doi.org/10.1371/journal.pone.0164873Mendes, G., Ramalho, J. F., Duarte, A., Pedrosa, A., Silva, A. C., Méndez, L., & Caneiras, C. (2022). First Outbreak of NDM-1-Producing Klebsiella pneumoniae ST11 in a Portuguese Hospital Centre during the COVID-19 Pandemic. Microorganisms, 10(2), 1–14. https://doi.org/10.3390/microorganisms10020251Navon-Venezia, S., Kondratyeva, K., & Carattoli, A. (2017). Klebsiella pneumoniae: A major worldwide source and shuttle for antibiotic resistance. FEMS Microbiology Reviews, 41(3), 252–275. https://doi.org/10.1093/femsre/fux013Nori, P., Cowman, K., Chen, V., Bartash, R., Szymczak, W., Madaline, T., Punjabi Katiyar, C., Jain, R., Aldrich, M., Weston, G., Gialanella, P., Corpuz, M., Gendlina, I., & Guo, Y. (2020). Bacterial and fungal co-infections in COVID-19 patients hospitalized during the New York city pandemic surge. Infection Control and Hospital Epidemiology, 2020, 1–5. https://doi.org/10.1017/ice.2020.368OECD. (2018). Stemming the Superbug Tide: Just A Few Dollars More. https://www.oecd.org/els/health-systems/Stemming-the-Superbug-Tide-Policy-Brief 2018.pdfOMS. (2017). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb ET_NM_WHO.pdf?ua=1Organización Mundial de la Salud [OMS]. (2022). Panel de la OMS sobre la enfermedad por coronavirus (COVID-19). https://covid19.who.int/Österblad, M., Kirveskari, J., Hakanen, A. J., Tissari, P., Vaara, M., & Jalava, J. (2012). Carbapenemase-producing enterobacteriaceae in Finland: The first years (2008-11). Journal of Antimicrobial Chemotherapy, 67(12), 2860–2864. https://doi.org/10.1093/jac/dks299Pintado, V., Ruiz-Garbajosa, P., Escudero-Sanchez, R., Gioia, F., Herrera, S., Vizcarra, P., Fortún, J., Cobo, J., Martín-Dávila, P., Morosini, M. I., Cantón, R., & Moreno, S. (2022). Carbapenemase-producing Enterobacterales infections in COVID-19 patients. Infectious Diseases, 54(1), 36–45. https://doi.org/10.1080/23744235.2021.1963471Pitout, J. D. D., Nordmann, P., & Poirel, L. (2015). Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. In Antimicrobial Agents and Chemotherapy (Vol. 59, Issue 10, pp. 5873–5884). American Society for Microbiology. https://doi.org/10.1128/AAC.01019-15Prezioso, S. M., Brown, N. E., & Goldberg, J. B. (2017). Elfamycins: inhibitors of elongation factor-Tu. Molecular Microbiology, 106(1), 22–34. https://doi.org/10.1111/mmi.13750PubMLST. (2022). Bases de datos públicas para tipificación molecular y diversidad del genoma microbiano. https://pubmlst.org/Pulzova, L., Navratilova, L., & Comor, L. (2017). Alterations in Outer Membrane Permeability Favor Drug-Resistant Phenotype of Klebsiella pneumoniae. Microbial Drug Resistance, 23(4), 413–420. https://doi.org/10.1089/mdr.2016.0017Remolina Granados, S. A., & Escobar Castaño, C. J. (2017). Descripción de Tipos de Carbapenemasas Expresadas en Klebsiella sp. y Pseudomonas aeruginosa en Hospitales de Tercer Nivel de la Ciudad de Bogotá, Estudio Descriptivo. Parte 1 [Tesis de Especialización, Universidad Nacional de Colombia]. https://repositorio.unal.edu.co/bitstream/handle/unal/62824/SergioA.RemolinaGrana dos.2017.pdf?sequence=1&isAllowed=yRojas, L. J., Weinstock, G. M., De La Cadena, E., Diaz, L., Rios, R., Hanson, B. M., Brown, J. S., Vats, P., Phillips, D. S., Nguyen, H., Hujer, K. M., Correa, A., Adams, M. D., Perez, F., Sodergren, E., Narechania, A., Planet, P. J., Villegas, M. V., Bonomo, R. T. A., & Arias, C. A. (2018). An analysis of the epidemic of klebsiella pneumoniae carbapenemase-producing k. pneumoniae: Convergence of two evolutionary mechanisms creates the “perfect storm.” Journal of Infectious Diseases, 217(1), 82–92. https://doi.org/10.1093/infdis/jix524Saavedra, S. Y., Bernal, J. F., Montilla-Escudero, E., Arévalo, S. A., Prada, D. A., Valencia, M. F., Moreno, J., Hidalgo, A. M., Garciá-Vega, Á. S., Abrudan, M., Argimón, S., Kekre, M., Underwood, A., Aanensen, D. M., Duarte, C., Donado Godoy, P., Abudahab, K., Harste, H., Muddyman, D., … Vegvari, C. (2021). Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs. Clinical Infectious Diseases, 73(Suppl 4), S290–S299. https://doi.org/10.1093/cid/ciab777Saini, V., Jain, C., Singh, N. P., Alsulimani, A., Gupta, C., Dar, S. A., Haque, S., & Das, S. (2021). Paradigm shift in antimicrobial resistance pattern of bacterial isolates during the covid-19 pandemic. Antibiotics, 10(8), 1–11. https://doi.org/10.3390/antibiotics10080954Samanta, I., & Bandyopadhyay, S. (2020). Klebsiella. Antimicrobial Resistance in Agriculture, 258, 153–169. https://doi.org/10.1016/b978-0-12-815770-1.00014-6Seemann, T. (2014). Prokka: Rapid prokaryotic genome annotation. Bioinformatics, 30(14), 2068–2069. https://doi.org/10.1093/bioinformatics/btu153Sepandi, M., Taghdir, M., Alimohamadi, Y., Afrashteh, S., & Hosamirudsari, H. (2020). Factors associated with mortality in COVID-19 patients: A systematic review and meta-analysis. Iranian Journal of Public Health, 49(7), 1211–1221. https://doi.org/10.18502/ijph.v49i7.3574Shelburne, S. A., Kim, J., Munita, J. M., Sahasrabhojane, P., Shields, R. K., Press, E. G., Li, X., Arias, C. A., Cantarel, B., Jiang, Y., Kim, M. S., Aitken, S. L., & Greenberg, D. E. (2017). Whole-genome sequencing accurately identifies resistance to extended spectrum β-lactams for major gram-negative bacterial pathogens. Clinical Infectious Diseases, 65(5), 738–745. https://doi.org/10.1093/cid/cix417Shelenkov, A., Petrova, L., Mironova, A., Zamyatin, M., Akimkin, V., & Mikhaylova, Y. (2022). Long-Read Whole Genome Sequencing Elucidates the Mechanisms of Amikacin Resistance in Multidrug-Resistant Klebsiella pneumoniae Isolates Obtained from COVID-19 Patients. Antibiotics, 11(10). https://doi.org/10.3390/antibiotics11101364Shon, A. S., Bajwa, R. P. S., & Russo, T. A. (2013). Hypervirulent (hypermucoviscous) Klebsiella Pneumoniae: A new and dangerous breed. Virulence, 4(2), 107–118. https://doi.org/10.4161/viru.22718Stamatakis, A. (2014). RAxML version 8: A tool for phylogenetic analysis and post analysis of large phylogenies. Bioinformatics, 30(9), 1312–1313. https://doi.org/10.1093/bioinformatics/btu033Suárez, C., & Gudiol, F. (2009). Beta-lactam antibiotics. Enfermedades Infecciosas y Microbiologia Clinica, 27(2), 116–129. https://doi.org/10.1016/j.eimc.2008.12.001Talero Osorio, D. C. (2022). Identificación de contigs asociados a plásmidos obtenidos a partir de secuenciación de genoma completo de aislamientos de Klebsiella pneumoniae. Universidad Nacional de Colombia. [Universidad Nacional de Colombia]. https://repositorio.unal.edu.co/handle/unal/81811T.Seemann. (2022a). mlst Github. https://github.com/tseemann/mlstT.Seemann. (2022b). snippy. https://github.com/tseemann/snippyThermo ScientificTM OxoidTM. (2020). Medios deshidratados. http://www.analisisavanzados.com/index.php/catalogo-general-de-productos oxoid?article=&id=119Tiri, B., Sensi, E., Marsiliani, V., Cantarini, M., Priante, G., Vernelli, C., Martella, L. A., Costantini, M., Mariottini, A., Andreani, P., Bruzzone, P., Suadoni, F., Francucci, M., Cirocchi, R., & Cappanera, S. (2020). Antimicrobial Stewardship Program, COVID 19, and Infection Control: Spread of Carbapenem-Resistant Klebsiella Pneumoniae Colonization in ICU COVID-19 Patients. What Did Not Work? Journal of Clinical Medicine, 9(9), 2744. https://doi.org/10.3390/jcm9092744Wilson, H., & Török, M. E. (2018). Extended-spectrum β-lactamase-producing and carbapenemase-producing Enterobacteriaceae. Microbial Genomics, 4(7). https://doi.org/10.1099/mgen.0.000197World Health Organization. (2020). Coronavirus disease 2019 (COVID-19): situation report, 51. World Health Organization. https://apps.who.int/iris/handle/10665/331475Wu, H., Li, D., Zhou, H., Sun, Y., Guo, ling, & Shen, D. (2017). Bacteremia and other body site infection caused by hypervirulent and classic Klebsiella pneumoniae. Microbial Pathogenesis, 104, 254–262. https://doi.org/10.1016/j.micpath.2017.01.049Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G. F., & Tan, W. (2020). A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine, 382(8), 727–733. https://doi.org/10.1056/nejmoa2001017Zhu, X., Ge, Y., Wu, T., Zhao, K., Chen, Y., Wu, B., Zhu, F., Zhu, B., & Cui, L. (2020). Co infection with respiratory pathogens among COVID-2019 cases Xiaojuan. Virus Research, 285. https://doi.org/https://doi.org/10.1016/j.virusres.2020.198005Klebsiella pneumoniaeAislamiento de PacientesResistencia antimicrobianaCarbapenemasasClonesSecuenciación de genoma completoInfecciones intrahospitalariasCOVID-19Antimicrobial resistanceCarbapenemasesClustersNosocomial infectionsWhole genome sequencingKlebsiella pneumoniaeEstudiantesInvestigadoresMaestrosPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/84398/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL38291096.2023.pdf38291096.2023.pdfTesis de Maestría en Ciencias-Microbiologíaapplication/pdf3646086https://repositorio.unal.edu.co/bitstream/unal/84398/2/38291096.2023.pdfb6f2c638999a50a3cfa6a2529aa49483MD52THUMBNAIL38291096.2023.pdf.jpg38291096.2023.pdf.jpgGenerated 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