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Background Carbapenem-resistant Pseudomonas aeruginosa are being increasingly described worldwide. Here, we investigated the molecular mechanisms underlying carbapenem resistance in an extremely drug-resistant P. aeruginosa isolate from a neonatal intensive care unit in Morocco. Materials and methods P. aeruginosa strain O82J1 was identified using MALDI-TOF-MS. Carba NP, immunochromatographic assay NG Carba5 and antimicrobial susceptibility testing using disc diffusion and microbroth were performed. Whole-genome sequencing using the Illumina and MinION technologies and different software packages available at the Center of Genomic Epidemiology were used to predict the resistome, sequence type and plasmid types. Results P. aeruginosa O82J1 co-expressed two metallo-β-lactamases, bla NDM-1 and bla VIM-2, and was susceptible to colistin and apramycin only. It belonged to ST773 that is frequently reported worldwide as a high-risk P. aeruginosa clone. The bla VIM-2 gene was integron-borne on a IncP-2 465-kb plasmid, whereas the bla NDM-1 gene was chromosomally encoded and embedded in an integrative conjugative element, probably at the origin of its acquisition. A total of 23 antimicrobial resistance genes were detected including a bla PER-1 ESBL gene, and an 16S-rRNA methyltransferase gene rmtB. Conclusions The isolation of XDR P. aeruginosa isolates expressing several carbapenemases in a neonatal intensive care unit is of great concern due to the reduced treatment options, relying only on colistin, but not recommended in neonates, and apramycin, not yet approved for human therapy. Concerns were further elevated due to the resistance to cefiderocol and ATM/AVI, two novel and last-resort antibiotics recommended to treat infections caused by Gram-negative bacteria, particularly XDR P. aeruginosa in adults. [ABSTRACT FROM AUTHOR]

Objectives: Neonatal sepsis caused by multidrug-resistant (MDR) bacteria has a high morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of multidrug resistance in bacteria responsible for neonatal sepsis were determined., Methods: From July to December 2019, documented bacteraemia from 524 neonates hospitalised in a neonatal intensive care unit in Morocco were collected. Whole-genome sequencing was used to characterise the resistome; multi-locus sequence typing was used to investigate phylogeny., Results: Among the 199 cases of documented bacteraemia, 40 (20%) and 20 (10%) were caused by MDR Klebsiella pneumoniae and Enterobacter hormaechei, respectively. Of these, 23 (38.5%) were early neonatal infections (≤3 days of life). Twelve different sequence types (STs) were observed among K. pneumoniae isolates, the most prevalent being ST1805 (n = 10) and ST307 (n = 8). Twenty-one K. pneumoniae isolates (53%) possessed the bla CTX-M-15 gene, six of which co-produced OXA-48; two, NDM-7; and two, OXA-48 and NDM-7. The bla OXA-48 gene was present in 11 K. pneumoniae isolates (27.5%); bla NDM-1 , in 13 (32.5%); and bla NDM-7 , in 4 (10.0%). Eighteen E. hormaechei isolates (90.0%) produced an extended-spectrum β-lactamase (ESBL). Three were SHV-12 producers that co-produced CMY-4 and NDM-1, and 15 were CTXM-15 producers, of which 6 co-produced OXA-48. Twelve different STs belonging to three different E. hormaechei subspecies were observed, with one to four isolates. K. pneumoniae and E. hormaechei isolates belonging to the same ST had less than 20 single nucleotide polymorphism differences and were found throughout the study period, highlighting their endemic presence in the neonatal intensive care unit., Conclusion: Thirty percent of neonatal sepsis cases (23 early and 37 late) were caused by highly drug-resistant carbapenemase- and/or ESBL-producing Enterobacterales., Competing Interests: Competing interests None to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)