Predicting Pseudomonas aeruginosa susceptibility phenotypes from whole genome sequence resistome analysis

Autor: Germán Bou, Cristina Seral, Juan Manuel Sánchez, Jennifer Villa, Pedro de la Iglesia, Julia Pita, Jorge Calvo, Jesús Oteo, Ma José Centelles, Ana Isabel López-Calleja, Carmen Gallegos, Noelia Arenal-Andrés, Antonio Oliver, José Carlos González, Fernando Artiles, Silvia Capilla, Teresa Alarcón, Laura Viñuela, Luis Martínez-Martínez, Ana González, Andrés Canut, María Isabel Sánchez, Bárbara Gomila, Emilia Cercenado, Raquel Elisa Rodríguez-Tarazona, Nelly Daniela Zurita, María Isabel Morosini, Susana Ramón, Alba Rivera, Cristina Pitart, Laura Zamorano, Irina Sánchez-Diener, Carla López-Causapé, Fraqncisco Javier Castillo-García, Alejandro Seoane, Desiré Gijón, David Mauricio Guzmán, Irene Merino, Manuel Antonio Rodríguez, Nieves Larrosa, Nuria Tormo, Javier Aznar, José A. Oteo, Ester del Barrio-Tofiño, María Dolores Quesada, Mar Olga Pérez-Moreno, Yolanda Sáenz, José Luis Barrios, María del Pilar Ortega, Francesc Marco, Irene Gracia, Inma López-Hernández, José Manuel Azcona-Gutiérrez, Emma Padilla, Gregoria Megías, Genoveva Yagüe, Inmaculada García, Beatriz Mirelis, Lina Martín, Eugenio Garduño, Rafael Cantón, María Luisa Pérez del Molino, José Andrés Agulla, Fátima Galán, Elena Riera, Yannick Hoyos, Fe Tubau, Salvador Giner, Fernando Chaves, José Antonio Lepe, Gema Barbeito, Laura Moreno, José Leiva, Juan Pablo Horcajada, Sara Cortes-Lara, Cristina Colmenarejo, María Cruz Pérez, Carmen Aspiroz, Marta García, Juan José González, Nora Mariela Martínez, Isabel Paz Vidal, Ma Victoria García
Rok vydání: 2020
Předmět:
Zdroj: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 27(11)
ISSN: 1469-0691
Popis: The aim was to develop and validate a Pseudomonas aeruginosa genotypic resistance score, based on analysis of the whole genome sequence resistome, to predict antimicrobial susceptibility phenotypes.A scoring system based on the analysis of mutation-driven resistance in 40 chromosomal genes and horizontally acquired resistance (Resfinder) was developed for ceftazidime, ceftolozane/tazobactam, meropenem, ciprofloxacin and tobramycin. Resistance genes/mutations were scored from 0 (no effect) to 1 (EUCAST clinical resistance). One hundred wild-type strains obtained from 51 different hospitals during a 2017 multicentre study were fully sequenced and analysed in order to define a catalogue of natural polymorphisms in the 40 chromosomal resistance genes. The capacity of genotypic score to predict the susceptibility phenotype was tested in 204 isolates randomly selected from the 51 hospitals (four from each hospital).The analysis of the 100 wild-type isolates yielded a catalogue of 455 natural polymorphisms in the 40 genes involved in mutational resistance. However, resistance mutations and high-risk clones (such as ST235) were also documented among a few wild-type isolates. Overall, the capacity of the genotypic score (0.5) for predicting phenotypic susceptibility (S + I in the case of meropenem) was very high (95-100%). In contrast, the capacity of the genotypic score to predict resistance (≥1) was far more variable depending on the agent. Prediction of meropenem clinical resistance was particularly low (18/39, 46.1%), whereas it classified clinical ceftolozane/tazobactam resistance in 100% (7/7) of cases.Although a margin for improvement was evidenced in this proof of concept study, an overall good correlation between the genotypic resistance score and the susceptibility profile was documented. Further refining of the scoring system, automatization and testing of large international cohorts should follow.
Databáze: OpenAIRE
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