Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs

Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging public health problem. This study explores the specifics of CRKP epidemiology in Colombia based on whole genome sequencing (WGS) of the National Reference Laboratory at Instituto Nacional de Salud (INS)’s 2013-2017 sample collection. Methods A total of 425 CRKP isolates from 21 departments were analyzed by HiSeq-X10® Illumina high-throughput sequencing. Bioinformatic analysis was performed, primarily using the pipelines developed collaboratively by the National Institute for Health Research Global Health Research Unit (GHRU) on Genomic Surveillance of AMR, and AGROSAVIA. Results Of the 425 CRKP isolates, 91.5% were carbapenemase-producing strains. The data support a recent expansion and the endemicity of CRKP in Colombia with the circulation of 7 high-risk clones, the most frequent being CG258 (48.39% of isolates). We identified genes encoding carbapenemases blaKPC-3, blaKPC-2, blaNDM-1, blaNDM-9, blaVIM-2, blaVIM-4, and blaVIM-24, and various mobile genetic elements (MGE). The virulence of CRKP isolates was low, but colibactin (clb3) was present in 25.2% of isolates, and a hypervirulent CRKP clone (CG380) was reported for the first time in Colombia. ST258, ST512, and ST4851 were characterized by low levels of diversity in the core genome (ANI> 99.9%). Conclusions The study outlines complex CRKP epidemiology in Colombia. CG258 expanded clonally and carries specific carbapenemases in specific MGEs, while the other high-risk clones (CG147, CG307, and CG152) present a more diverse complement of carbapenemases. The specifics of the Colombian situation stress the importance of WGS-based surveillance to monitor evolutionary trends of STs, MGE, and resistance and virulence genes. summary In Colombia, the dissemination of carbapenemases in carbapenem-resistant Klebsiella pneumoniae is attributed to horizontal gene transfer and successful circulation of CG258, and, to a lesser extent, other clones such as ST307, ST147, and ST152.

[1]  Stephen C. Watts,et al.  Genomic surveillance framework and global population structure for Klebsiella pneumoniae , 2020, bioRxiv.

[2]  J. Parkhill,et al.  Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae , 2020, Proceedings of the National Academy of Sciences.

[3]  F. Cardinale,et al.  Phenotypical and molecular assessment of the virulence potential of KPC-3-producing Klebsiella pneumoniae ST392 clinical isolates. , 2020, Microbiological research.

[4]  S. Salipante,et al.  Whole Genome Sequencing of Peruvian Klebsiella pneumoniae Identifies Novel Plasmid Vectors Bearing Carbapenem Resistance Gene NDM-1 , 2020, Open forum infectious diseases.

[5]  Marietta L. Lagrada,et al.  Integrating whole-genome sequencing within the National Antimicrobial Resistance Surveillance Program in the Philippines , 2020, Nature Communications.

[6]  Ling Guo,et al.  Prevalence and characteristics of surgical site hypervirulent Klebsiella pneumoniae isolates , 2020, Journal of clinical laboratory analysis.

[7]  K. Holt,et al.  Population genomics of Klebsiella pneumoniae , 2020, Nature Reviews Microbiology.

[8]  Yonghong Xiao,et al.  Novel Subclone of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 with Enhanced Virulence and Transmissibility, China , 2020, Emerging infectious diseases.

[9]  Ruobing Wang,et al.  The transferability and evolution of NDM-1 and KPC-2 co-producing Klebsiella pneumoniae from clinical settings , 2020, EBioMedicine.

[10]  V. Seija,et al.  First characterization of K. pneumoniae ST11 clinical isolates harboring blaKPC-3 in Latin America. , 2019, Revista Argentina de microbiologia.

[11]  J. N. Jiménez,et al.  Risk factors and survival of patients infected with carbapenem-resistant Klebsiella pneumoniae in a KPC endemic setting: a case-control and cohort study , 2019, BMC Infectious Diseases.

[12]  K. Beis,et al.  OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo , 2019, Nature Communications.

[13]  L. Poirel,et al.  Cooccurrence of NDM-1, ESBL, RmtC, AAC(6′)-Ib, and QnrB in Clonally Related Klebsiella pneumoniae Isolates Together with Coexistence of CMY-4 and AAC(6′)-Ib in Enterobacter cloacae Isolates from Saudi Arabia , 2019, BioMed research international.

[14]  Richard J. Goater,et al.  Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread , 2019, Nature Microbiology.

[15]  A. Duarte,et al.  Community- and Hospital-Acquired Klebsiella pneumoniae Urinary Tract Infections in Portugal: Virulence and Antibiotic Resistance , 2019, Microorganisms.

[16]  Z. Zong,et al.  NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings , 2019, Clinical Microbiology Reviews.

[17]  J. Bengoechea,et al.  Klebsiella pneumoniae infection biology: living to counteract host defences , 2018, FEMS microbiology reviews.

[18]  K. Holt,et al.  Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae , 2018, bioRxiv.

[19]  K. Holt,et al.  Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae , 2018, Genome Medicine.

[20]  K. Holt,et al.  Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations , 2018, Microbial genomics.

[21]  Prateek Shrivastava,et al.  World health organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics , 2018 .

[22]  M. Adams,et al.  Genomic epidemiology of global VIM-producing Enterobacteriaceae , 2017, The Journal of antimicrobial chemotherapy.

[23]  Alessandra Carattoli,et al.  Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance , 2017, FEMS microbiology reviews.

[24]  N. Woodford,et al.  Diversity, virulence, and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone , 2017, Microbial genomics.

[25]  M. Adams,et al.  An Analysis of the Epidemic of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae: Convergence of Two Evolutionary Mechanisms Creates the “Perfect Storm” , 2017, The Journal of infectious diseases.

[26]  Mauricio Beltrán,et al.  Resultados de la vigilancia nacional de resistencia antimicrobiana en infecciones asociadas a la atención en salud en enterobacterias y Gram negativos no fermentadores, Colombia 2012-2014 , 2016 .

[27]  Khalil Abudahab,et al.  Microreact: visualizing and sharing data for genomic epidemiology and phylogeography , 2016, Microbial genomics.

[28]  K. Holt,et al.  Identification of Klebsiella capsule synthesis loci from whole genome data , 2016, bioRxiv.

[29]  M. Adams,et al.  Initial Assessment of the Molecular Epidemiology of blaNDM-1 in Colombia , 2016, Antimicrobial Agents and Chemotherapy.

[30]  B. Kreiswirth,et al.  A Two-Year Surveillance in Five Colombian Tertiary Care Hospitals Reveals High Frequency of Non-CG258 Clones of Carbapenem-Resistant Klebsiella pneumoniae with Distinct Clinical Characteristics , 2015, Antimicrobial Agents and Chemotherapy.

[31]  P. Nordmann,et al.  Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance , 2015, Antimicrobial Agents and Chemotherapy.

[32]  C. Arias,et al.  Dissemination of High-Risk Clones of Extensively Drug-Resistant Pseudomonas aeruginosa in Colombia , 2015, Antimicrobial Agents and Chemotherapy.

[33]  A. von Haeseler,et al.  IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies , 2014, Molecular biology and evolution.

[34]  R. Bonomo,et al.  Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. , 2014, Trends in microbiology.

[35]  Sharon J. Peacock,et al.  Whole-genome sequencing to control antimicrobial resistance , 2014, Trends in genetics : TIG.

[36]  R. Evans European Centre for Disease Prevention and Control. , 2014, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[37]  Hui Wang,et al.  Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. , 2013, The Lancet. Infectious diseases.

[38]  V. Zahner,et al.  Update of the molecular epidemiology of KPC-2-producing Klebsiella pneumoniae in Brazil: spread of clonal complex 11 (ST11, ST437 and ST340). , 2013, The Journal of antimicrobial chemotherapy.

[39]  Javier Antonio Escobar Pérez,et al.  Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Neonatal Unit in Colombia , 2013, Antimicrobial Agents and Chemotherapy.

[40]  Y. Carmeli,et al.  Containment of a country-wide outbreak of carbapenem-resistant Klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[41]  Y. Qi,et al.  ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China. , 2011, The Journal of antimicrobial chemotherapy.

[42]  Natalia C Rosas,et al.  Novel VIM Metallo-β-Lactamase Variant, VIM-24, from a Klebsiella pneumoniae Isolate from Colombia , 2011, Antimicrobial Agents and Chemotherapy.

[43]  J. Quinn,et al.  Intercontinental spread from Israel to Colombia of a KPC-3-producing Klebsiella pneumoniae strain. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[44]  Y. Carmeli,et al.  Molecular Epidemiology of KPC-Producing Klebsiella pneumoniae Isolates in the United States: Clonal Expansion of Multilocus Sequence Type 258 , 2009, Antimicrobial Agents and Chemotherapy.

[45]  J. Quinn,et al.  First Detection of the Plasmid-Mediated Class A Carbapenemase KPC-2 in Clinical Isolates of Klebsiella pneumoniae from South America , 2006, Antimicrobial Agents and Chemotherapy.