Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)

Ceftolozane-tazobactam (C/T) is frequently used for infections caused by multidrug-resistant (MDR)-Enterobacterales isolates. Whole-genome sequencing (WGS, Illumina-Hiseq 4000/NovaSeq 6000, OGC, UK) was to study the population structure, resistome and virulome of C/T-susceptible -resistant MDR Escherichia spp. (n=30) Klebsiella (n=78) isolates, recovered from lower respiratory, intra-abdominal urinary tract ICU patients 11 Portuguese Hospitals (STEP study, 2017-2018). Minimum inhibitory concentrations (MICs) were determined (ISO-broth microdilution, breakpoints EUCAST-2020). In spp., a weak concordance between phenotypic WGS method (P=0.051) observed in carbapenemase detection (3/30) [blaVIM-2 (2/3), blaKPC-3 (1/3)]; VIM-2-Escherichia coli isolates only KPC-3-Escherichia marmotae producer showed C/T-resistance. Overall, CTX-M-15-E. coli-ST131-O25:H4-H30-Rx (11/30) most frequent subclone, followed CTX-M-27-E. coli-ST131-O25:H4-H30 (4/4). Moreover, wide detected all E. Among [K. pneumoniae (67/78), K. aerogenes (7/78), oxytoca (2/78), variicola (2/78)], (P<0.001) genomic (21/78) [blaKPC-3 (14/21), blaOXA-48 (3/21), blaOXA-181 (3/21)]. A high correlation C/T-resistance established (P<0.05). clonal diversity observed, mainly KPC-3-producing An extensive whereas virulence determinants mostly identified producers (P<0.001). powerful tool typing characterization microbiological MDR-Enterobacterales pathogens. Furthermore, genes are associated with but other mechanisms might also be involved.