Browsing by Author "García, P."
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- ItemAcquisition of resistance to ceftazidime-avibactam during infection treatment in Pseudomonas aeruginosa through D179Y mutation in one of two blaKPC-2 gene copies without losing carbapenem resistance(2022) García, P.; Brito, B.; Alcalde-Rico, M.; Munita, J.M.; Martínez, J.R.W.; Olivares-Pacheco, J.; Quiroz, V.; Wozniak, A.Ceftazidime/Avibactam (CAZ/AVI) is frequently used to treat KPC-producing Pseudomonas aeruginosa (KPC-PA) and Enterobacterales. CAZ/AVI resistance is driven by several mechanisms. In P. aeruginosa this mainly occurs through alteration of AmpC, porins, and/or efflux pump overexpression, whereas in Enterobacterales it frequently occurs through D179Y substitution in the active site of KPC enzyme. This aminoacid change abolishes AVI binding to the KPC active site, hence inhibition is impaired. However, this substitution also decreases KPC-mediated resistance to carbapenems (“see-saw” effect). The goal of this work was to characterize the in vivo acquisition of CAZ/AVI resistance through D179Y substitution in a KPC-PA isolated from a hospitalized patient after CAZ/AVI treatment. Two KPC-PA isolates were obtained. The first isolate, PA-1, was obtained before CAZ/AVI treatment and was susceptible to CAZ/AVI. The second isolate, PA-2, was obtained after CAZ/AVI treatment and exhibited high-level CAZ/AVI resistance. Characterization of isolates PA-1 and PA-2 was performed through short and long-read whole genome sequencing analysis. The hybrid assembly showed that PA-1 and PA-2A had a single plasmid of 54,030 bp, named pPA-1 and pPA-2 respectively. Each plasmid harbored two copies of the blaKPC-containing Tn4401b transposon. However, while pPA-1 carried two copies of blaKPC-2, pPA-2 had one copy of blaKPC-2 and one copy of blaKPC-33, the allele with the D179Y substitution. Interestingly, isolate PA-2 did not exhibit the “see-saw” effect. The blaKPC-33 allele was detected only through hybrid assembly using a long-read-first approach. The present work describes a KPC-PA isolate harboring a plasmid-borne CAZ/AVI resistance mechanism based on two copies of blaKPC-2-Tn4401b and D179Y mutation in one of them, that is not associated with loss of resistance to carbapenems. These findings highlight the usefulness of a fine-tuned combined analysis of short and long-read data to detect similar emerging resistance mechanisms.
- ItemIntegrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate(2020) Pandey, A.; Stawiski, E. W.; Durinck, S.; Gowda, H.; Goldstein, L. D.; Barbhuiya, M. A.; Schroder, M. S.; Sreenivasamurthy, S. K.; Bizama, Carolina; Roa Strauch, Juan Carlos Enrique; Kim, S. W.; Phalke, S.; Suryamohan, K.; Lee, K.; Chakraborty, P.; Kode, V.; Shi, X. S.; Chatterjee, A.; Datta, K.; Khan, A. A.; Subbannayya, T.; Wang, J.; Chaudhuri, S.; Gupta, S.; Shrivastav, B. R.; Jaiswal, B. S.; Poojary, S. S.; Bhunia, S.; García, P.; Rosa, L.; Kwon, W.; Kim, H.; Han, Y.; Yadav, T. D.; Ramprasad, V. L.; Chaudhuri, A.; Modrusan, Z.; Tiwari, P. K.; Jang, J. Y.; Seshagiri, S.
- ItemPharmacokinetics of posaconazol in the prophylaxis and treatment of invasive fungal infection in immunocompromised children in a pediatric hospital,Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico(2018) Valenzuela, R.; García, P.; Barraza, M.; Palma, J.; Catalán, P.; Santolaya, M.E.; Torres, J.P.; Morales Vallespín, J.
- ItemPrimer aislado de Pseudomonas aeruginosa productora de Sao Paulo metalo-β-lactamasa (SPM-1) en un paciente chileno(2021) Wozniak, A.; Rodríguez, N.; Alcalde-Rico, M.; Castillo, C.; García, P.Las enzimas VIM, IMP, y NDM son carbapenemasas de tipo metalo-β-lactamasas (MBLs) que se encuentran ampliamente distribuidas en el mundo. La SPM-1 (Sao Paulo metalo-β-lactamasa) es una MBL que fue descrita en Pseudomonas aeruginosa en Sao Paulo (Brasil) en 2002. Comunicamos por primera vez la presencia de SPM-1 en Chile, en un aislado de P aeruginosa resistente a meropenem e imipenem, detectado en un cultivo rectal de vigilancia de carbapenemasas desde un paciente internado en nuestra institución. La secuencia del producto de la RPC fue 100% idéntica a la secuencia de SPM-1 reportada en Brasil. El paciente tenía antecedentes de una angioplastía realizada en Brasil en 2004-2005. Como consecuencia de este hallazgo, la detección de SPM mediante RPC será incorporada a la búsqueda de rutina de carbapenemasas en P aeruginosa.
- ItemSocioeconomic factors associated with antimicrobial resistance of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in Chilean hospitals (2008-2017)(2020) Allel, K.; García, P.; Labarca L., Jaime; Munita, J. M.; Rendic, M.; Undurraga Fourcade, Eduardo Andrés