title: Development of a rat central venous catheter model for evaluation of vaccines to prevent Staphylococcus epidermidis and Staphylococcus aureus early biofilms.
abstract: Indwelling central venous catheters are a common and important source of nosocomial Staphylococcus epidermidis and S. aureus infections, causing increased morbidity and mortality during hospitalization. A model was developed to reflect the clinical situation of catheter colonization by transient hematogeneously spread staphylococci, in order to investigate potential vaccine candidates. Rats were cannulated in the right jugular vein, followed by challenge through the tail vein with either S. epidermidis RP62a, or S. aureus Becker. At 24 hr post challenge, colonizing bacteria were found to be present on the catheter in an early biofilm, as evidenced by the presence of polysaccharide intercellular adhesin (PIA). For vaccination studies, rats were first immunized, surgically cannulated, and then challenged via the tail vein. At 24 hr post challenge, the catheters were harvested and cultured on mannitol salt agar plates. The catheters were scored as positive if there was outgrowth of bacterial colonies, and negative if no colonies were observed. A S. epidermidis antigen (SERP0630, MenD), and a S. aureus antigen (SACOL1138, iron regulated surface determinant B, IsdB) were found to have significant protective activity in this model, compared to mock immunized controls. Using SERP0630 as the test immunogen, it was also determined that a single vaccination of rats after cannulation was sufficient for significant catheter protection. This model may be used to evaluate antigens for protective activity against transient hematogenous spread of staphylococci resulting in catheter colonization and early biofilm formation.
authors.affiliation: Merck Research Labs, Merck, Sharp & Dohme, Inc, West Point, PA, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Ebert
authors.forename: Sharon
authors.initials: S
authors.lastname: Smith
authors.forename: Greg
authors.initials: G
authors.lastname: Pancari
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wu
authors.forename: Julie
authors.initials: J
authors.lastname: Zorman
authors.forename: Desmond
authors.initials: D
authors.lastname: Clark
authors.forename: Jim
authors.initials: J
authors.lastname: Cook
authors.forename: Carol
authors.initials: C
authors.lastname: Burns
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Antonello
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.forename: Eszter
authors.initials: E
authors.lastname: Nagy
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinke
authors.forename: Tessie
authors.initials: T
authors.lastname: McNeely
mesh_terms: D000818:Animals; D018441:Biofilms; D055499:Catheter-Related Infections / Q000517:prevention & control*; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D005260:Female; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000276:immunology*
chemical_list: D013209:Staphylococcal Vaccines