AUTHOR=Cañada-García Javier E. , Moure Zaira , Sola-Campoy Pedro J. , Delgado-Valverde Mercedes , Cano María E. , Gijón Desirèe , González Mónica , Gracia-Ahufinger Irene , Larrosa Nieves , Mulet Xavier , Pitart Cristina , Rivera Alba , Bou Germán , Calvo Jorge , Cantón Rafael , González-López Juan José , Martínez-Martínez Luis , Navarro Ferran , Oliver Antonio , Palacios-Baena Zaira R. , Pascual Álvaro , Ruiz-Carrascoso Guillermo , Vila Jordi , Aracil Belén , Pérez-Vázquez María , Oteo-Iglesias Jesús , the GEMARA/GEIRAS-SEIMC/REIPI CARB-ES-19 Study Group , Martínez Ramírez Mariela , Zamarrón Pilar , Albert Hernández Miriam , Pilar Ortega Lafont M. , Cercenado Emilia , del Rosario and Jose Luis Perez Arellano Cristobal , Lecuona María , López-Urrutia Lorente Luis , Leiva and José Luis del Pozo José , Giner and Juan Frasquet Salvador , Garcia Agudo and Soledad Illescas Lidia , de la Iglesia Pedro , Sánchez Benito Rosario , Garduño Eugenio , Isabel Fernández Natal and Marta Arias Ma , Lamata Subero Marta , Olga Pérez Moreno Mar , Isabel López-Calleja Ana , Torres Sopena Luis , Manuel Azcona José , Belles Alba , García González Mercè , Valverde Troya and Begoña Palop Miriam , García Garrote Fernando , Luis Barrios Andrés Jose , López Soria Leyre , Gimeno Adelina , Sabater Susana , Clapés Sanchez Ester , Villa Jennifer , Iglesias Nuñez Nuria , Sánchez Arroyo Rafael , García García Inmaculada , Hernando Susana , Seral Cristina , Castillo Javier , Riquelme Bravo Eva , Sainz de Baranda Caridad , Esparcia Rodríguez Oscar , Gaitán Jorge , Huertas María , José Rodríguez Escudero M.a , Aldea Carmen , Sanchez Nerea , Casabella Pernas Antonio , Dolores Quesada Ma , Pilar Chocarro Maria , Javier Ramos Francisco , Martí Sala Carmina , Mora Laura , Clavijo Encarnación , Chueca Natalia , García Federico , Gutierrez Fernández José , Manuel Sánchez Hospital de Jérez Juan , Galán Sánchez Fátima , Liébana Carmen , Roldán Carolina , Isabel Cabeza Ma , María Saavedra José , Teresa Cabezas Fernández Ma , Martínez Lamas Lucía , Rey Cao Sonia , Isabel Paz Vidal Ma , Elisa Rodríguez Tarazona Raquel , Coira Nieto Amparo , Luisa Pérez del Molino Bernal Ma , Gomáriz Díaz María , Vidal-García Matxalen , Luis Díaz de Tuesta Jose , García Bravo Moises , Tinajas Almudena , Canut Blasco Andrés , Luz Albina Cordón Rodriguez Ma , Gonzalo Jiménez Nieves , Yagüe Guirao Genoveva , Tubau Quintano Fe , Aspiroz Carmen , Prim Nuria , Rodríguez-Baño Jesús TITLE=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 JOURNAL=Frontiers in Microbiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.918362 DOI=10.3389/fmicb.2022.918362 ISSN=1664-302X ABSTRACT=Objectives

CARB-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.

Methods

In 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.

Results

In 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).

Conclusion

This 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.