Tracing Staphylococcus capitis and Staphylococcus epidermidis strains causing septicemia in extremely preterm infants to the skin, mouth, and gut microbiota.

Abstract

Coagulase-negative staphylococci (CoNS) comprise about 50 species, some of which cause septicemia in preterm neonates. CoNS establish early on the skin and in the oral and gut microbiota, from where they may spread to the bloodstream. The colonization pattern preceding septicemia is not well-defined. Forty-two extremely preterm neonates (≤28 + 0 gestational weeks) were followed from birth to 2 months with regular sampling and culturing of the skin and oral and gut microbiota. Blood samples were drawn upon clinical suspicion of septicemia and cultured. CoNS species were identified using matrix-assisted laser-desorption ionization time of flight mass spectrometry (MALDI-TOF). Random amplified polymorphic DNA was used for strain typing, and strains were characterized regarding biofilm production and virulence gene carriage. CoNS blood isolates underwent whole genome sequencing. Staphylococcus epidermidis represented 72% of the CoNS isolates on skin or mucous membranes, followed by Staphylococcus capitis (13%) and Staphylococcus haemolyticus (7%). CoNS septicemia was diagnosed in nine infants, yielding 11 septicemia isolates: seven S. capitis and four S. epidermidis, of which nine were further analyzed. The S. capitis septicemia isolates belonged to the NRCS-A clone. Two-thirds of the septicemia strains were traced back to the commensal microbiota. Colonization of the oral cavity by S. capitis was significantly associated with CoNS septicemia development, although the blood-borne S. capitis strains were more commonly found on the skin than in the mouth prior to invasion. Biofilm production was not associated with septicemia. Our results implicate CoNS colonization as a step that precedes septicemia in preterm neonates. Early colonization of the oral cavity by S. capitis may represent a particular risk.

Importance: Septicemia is a major cause of morbidity in preterm infants. Coagulase-negative staphylococci (CoNS) can colonize skin, oral cavity, and intestines and are a common cause of septicemia in this group. The relation between CoNS colonization pattern at the species and strain level and septicemia has scarcely been studied. We mapped colonization of the skin, oral cavity, and intestines by CoNS species in extremely preterm infants and speciated and strain-typed the skin, mucosal, and blood isolates. Two-thirds of the CoNS septicemia blood strains, including a majority of S. capitis strains belonging to the NRCS-A clone, were tracked to the commensal microbiota. We demonstrated that CoNS species differ in their colonization patterns, whereby S. capitis was primarily a skin colonizer. However, its colonization of the oral cavity was enhanced among infants developing septicemia. Our study provides a starting point for further explorations of the relationship between CoNS colonization and septicemia in preterm infants.