Producción CyT
KPC-2 allelic variants in Klebsiella pneumoniae isolates resistant to ceftazidime-avibactam from Argentina: bla KPC-80 , bla KPC-81 , bla KPC-96 and bla KPC-97
Articulo
Autoría:
SANZ, MARÍA BELÉN ; Pasteran, Fernando ; de Mendieta, Juan Manuel ; Brunetti, Florencia ; Albornoz, Ezequiel ; Rapoport, Melina ; Lucero, Celeste ; Errecalde, Laura ; Nuñez, Maria Rosa ; Monge, Renata ; Pennini, Magdalena ; Power, Pablo ; Corso, Alejandra ; Gomez, Sonia A.Fecha:
2024Editorial y Lugar de Edición:
American Society for MicrobiologyRevista:
Microbiology Spectrum, vol. 12 American Society for MicrobiologyResumen *
Ceftazidime-avibactam (CZA) therapy has significantly improved survival rates for patients infected by carbapenem-resistant bacteria, including KPC producers. However, resistance to CZA is a growing concern, attributed to multiple mechanisms. In this study, we characterized four clinical CZA-resistant Klebsiella pneumoniae isolates obtained between July 2019 and December 2020. These isolates expressed novel allelic variants of blaKPC-2 resulting from changes in hotspots of the mature protein, particularly in loops surrounding the active site of KPC. Notably, KPC-80 had an K269_D270insPNK mutation near the Lys270-loop, KPC-81 had a del_I173 mutation within the Ω-loop, KPC-96 showed a Y241N substitution within the Val240-loop and KPC-97 had an V277_I278insNSEAV mutation within the Lys270-loop. Three of the four isolates exhibited low-level resistance to imipenem (4 µg/mL), while all remained susceptible to meropenem. Avibactam and relebactam effectively restored carbapenem susceptibility in resistant isolates. Cloning mutant blaKPC genes into pMBLe increased imipenem MICs in recipient Escherichia coli TOP10 for blaKPC-80, blaKPC-96, and blaKPC-97 by two dilutions; again, these MICs were restored by avibactam and relebactam. Frameshift mutations disrupted ompK35 in three isolates. Additional resistance genes, including blaTEM-1, blaOXA-18 and blaOXA-1, were also identified. Interestingly, three isolates belonged to clonal complex 11 (ST258 and ST11) and one to ST629. This study highlights the emergence of CZA resistance including unique allelic variants of blaKPC-2 and impermeability. Comprehensive epidemiological surveillance and in-depth molecular studies are imperative for understanding and monitoring these complex resistance mechanisms, crucial for effective antimicrobial treatment strategies. Información suministrada por el agente en SIGEVAPalabras Clave
KPCceftazidime/avibactamKlebsiella pneumoniaeallelic variant