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Abstract：
An emergence of multidrug-resistant (MDR) Staphylococcus haemolyticus 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 S. haemolyticus infection, focusing on clinical outcomes. Forty-eight MDR S. haemolyticus strains, isolated from neonates between October 2019 and July 2022, were investigated using routine in vitro procedures and whole-genome sequencing. Additionally, five S. haemolyticus isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal S. haemolyticus was significantly associated with low birth weight, lower gestational age, and central catheter use (p < 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 S. haemolyticus 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 in silico to be resistant to methicillin, erythromycin, aminoglycosides, and fluoroquinolones, consistent with in vitro antibiotic susceptibility tests. Moreover, in silico 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 S. haemolyticus 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.
摘要：
在法国南部尼姆斯大学医院的新生儿重症监护病房（NICU）中观察到了多药耐药（MDR）溶血葡萄球菌的出现。对96例新生儿进行了病例对照分析，为了确定与溶血链球菌感染相关的危险因素，关注临床结果。48株MDR溶血链球菌，从2019年10月至2022年7月之间的新生儿中分离，我们使用常规体外程序和全基因组测序进行了研究。此外,对来自成年患者的5个溶血链球菌分离株进行了测序,以确定在医院环境中循环的菌群.新生儿溶血链球菌的发病率与低出生体重显著相关,较低的胎龄，和使用中央导管（p<0.001）。脓毒症是该系列中最常见的临床表现（20/46，43.5％），并与5例死亡有关。基于全基因组分析,预测了三种溶血链球菌基因型：ST1（6/53，11%），ST25（3/53，5.7%），和ST29（44/53，83%），其中包括II-A子集群，主要出现在新生儿科。所有菌株均经过硅分析，对甲氧西林具有抗性，红霉素,氨基糖苷类,和氟喹诺酮类药物,与体外抗生素药敏试验一致。此外，生物膜形成和毒力编码基因的计算机预测支持ST29与严重临床结局的关联,而NICU中的持久性可以通过防腐剂和重金属抗性编码基因的存在来解释。溶血链球菌ST29亚簇II-A分离株的克隆性证实了引起严重感染的医疗保健传播。基于这些结果,加强卫生措施对于根除MDR菌株的医院传播是必要的。
