Emergence of multidrug-resistant <i>Staphylococcus haemolyticus</i> in neonatal intensive care unit in Southern France, a genomic study

Abstract

An emergence of multidrug-resistant (MDR) <i>Staphylococcus haemolyticus</i> has been observed in the neonatal intensive care unit (NICU) of Nîmes University Hospital in southern France. A case-control analysis was conducted on 96 neonates, to identify risk factors associated with <i>S. haemolyticus</i> infection, focusing on clinical outcomes. Forty-eight MDR <i>S. haemolyticus</i> strains, isolated from neonates between October 2019 and July 2022, were investigated using routine <i>in vitro</i> procedures and whole-genome sequencing. Additionally, five <i>S. haemolyticus</i> isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal <i>S. haemolyticus</i> was significantly associated with low birth weight, lower gestational age, and central catheter use (<i>p </i>< 0.001). Sepsis was the most frequent clinical manifestation in this series (20/46, 43.5%) and was associated with five deaths. Based on whole-genome analysis, three <i>S. haemolyticus</i> genotypes were predicted: ST1 (6/53, 11%), ST25 (3/53, 5.7%), and ST29 (44/53, 83%), which included the subcluster II-A, predominantly emerging in the neonatal department. All strains were profiled <i>in silico</i> to be resistant to methicillin, erythromycin, aminoglycosides, and fluoroquinolones, consistent with <i>in vitro</i> antibiotic susceptibility tests. Moreover, <i>in silico</i> prediction of biofilm formation and virulence-encoding genes supported the association of ST29 with severe clinical outcomes, while the persistence in the NICU could be explained by the presence of antiseptic and heavy metal resistance-encoding genes. The clonality of <i>S. haemolyticus</i> ST29 subcluster II-A isolates confirms healthcare transmission causing severe infections. Based on these results, reinforced hygiene measures are necessary to eradicate the nosocomial transmission of MDR strains.