Frontiers in Microbiology (Jun 2022)

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

  • Javier E. Cañada-García,
  • Javier E. Cañada-García,
  • Zaira Moure,
  • Pedro J. Sola-Campoy,
  • Mercedes Delgado-Valverde,
  • Mercedes Delgado-Valverde,
  • María E. Cano,
  • Desirèe Gijón,
  • Desirèe Gijón,
  • Mónica González,
  • Mónica González,
  • Irene Gracia-Ahufinger,
  • Irene Gracia-Ahufinger,
  • Nieves Larrosa,
  • Nieves Larrosa,
  • Xavier Mulet,
  • Xavier Mulet,
  • Cristina Pitart,
  • Alba Rivera,
  • Germán Bou,
  • Germán Bou,
  • Jorge Calvo,
  • Jorge Calvo,
  • Rafael Cantón,
  • Rafael Cantón,
  • Juan José González-López,
  • Juan José González-López,
  • Luis Martínez-Martínez,
  • Luis Martínez-Martínez,
  • Luis Martínez-Martínez,
  • Ferran Navarro,
  • Antonio Oliver,
  • Antonio Oliver,
  • Zaira R. Palacios-Baena,
  • Zaira R. Palacios-Baena,
  • Zaira R. Palacios-Baena,
  • Álvaro Pascual,
  • Álvaro Pascual,
  • Álvaro Pascual,
  • Guillermo Ruiz-Carrascoso,
  • Jordi Vila,
  • Jordi Vila,
  • Belén Aracil,
  • Belén Aracil,
  • María Pérez-Vázquez,
  • María Pérez-Vázquez,
  • Jesús Oteo-Iglesias,
  • Jesús Oteo-Iglesias,
  • the GEMARA/GEIRAS-SEIMC/REIPI CARB-ES-19 Study Group,
  • Mariela Martínez Ramírez,
  • Pilar Zamarrón,
  • Miriam Albert Hernández,
  • M. Pilar Ortega Lafont,
  • Emilia Cercenado,
  • Cristobal del Rosario and Jose Luis Perez Arellano,
  • María Lecuona,
  • Luis López-Urrutia Lorente,
  • José Leiva and José Luis del Pozo,
  • Salvador Giner and Juan Frasquet,
  • Lidia Garcia Agudo and Soledad Illescas,
  • Pedro de la Iglesia,
  • Rosario Sánchez Benito,
  • Eugenio Garduño,
  • Ma Isabel Fernández Natal and Marta Arias,
  • Marta Lamata Subero,
  • Mar Olga Pérez Moreno,
  • Ana Isabel López-Calleja,
  • Luis Torres Sopena,
  • José Manuel Azcona,
  • Alba Belles,
  • Mercè García González,
  • Miriam Valverde Troya and Begoña Palop,
  • Fernando García Garrote,
  • Jose Luis Barrios Andrés,
  • Leyre López Soria,
  • Adelina Gimeno,
  • Susana Sabater,
  • Ester Clapés Sanchez,
  • Jennifer Villa,
  • Nuria Iglesias Nuñez,
  • Rafael Sánchez Arroyo,
  • Inmaculada García García,
  • Susana Hernando,
  • Cristina Seral,
  • Javier Castillo,
  • Eva Riquelme Bravo,
  • Caridad Sainz de Baranda,
  • Oscar Esparcia Rodríguez,
  • Jorge Gaitán,
  • María Huertas,
  • M.a José Rodríguez Escudero,
  • Carmen Aldea,
  • Nerea Sanchez,
  • Antonio Casabella Pernas,
  • Ma Dolores Quesada,
  • Maria Pilar Chocarro,
  • Francisco Javier Ramos,
  • Carmina Martí Sala,
  • Laura Mora,
  • Encarnación Clavijo,
  • Natalia Chueca,
  • Federico García,
  • José Gutierrez Fernández,
  • Juan Manuel Sánchez Hospital de Jérez,
  • Fátima Galán Sánchez,
  • Carmen Liébana,
  • Carolina Roldán,
  • Ma Isabel Cabeza,
  • José María Saavedra,
  • Ma Teresa Cabezas Fernández,
  • Lucía Martínez Lamas,
  • Sonia Rey Cao,
  • Ma Isabel Paz Vidal,
  • Raquel Elisa Rodríguez Tarazona,
  • Amparo Coira Nieto,
  • Ma Luisa Pérez del Molino Bernal,
  • María Gomáriz Díaz,
  • Matxalen Vidal-García,
  • Jose Luis Díaz de Tuesta,
  • Moises García Bravo,
  • Almudena Tinajas,
  • Andrés Canut Blasco,
  • Ma Luz Albina Cordón Rodriguez,
  • Nieves Gonzalo Jiménez,
  • Genoveva Yagüe Guirao,
  • Fe Tubau Quintano,
  • Carmen Aspiroz,
  • Nuria Prim,
  • Jesús Rodríguez-Baño

DOI
https://doi.org/10.3389/fmicb.2022.918362
Journal volume & issue
Vol. 13

Abstract

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ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.

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