Multidrug-resistant Enterobacterales responsible for septicaemia in a neonatal intensive care unit in Morocco

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 extendedspectrum beta-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 drugresistant carbapenemase- and/or ESBL-producing Enterobacterales.

Automated summary

The molecular mechanisms of multidrug resistance in bacteria responsible for neonatal sepsis were investigated. Whole-genome sequencing and multi-locus sequence typing were used to characterize the resistome and investigate phylogeny. Among the documented bacteraemia cases, 20% were caused by multidrug-resistant Klebsiella pneumoniae and 10% were caused by multidrug-resistant Enterobacter hormaechei.