title: Dynamical system analysis of Staphylococcus epidermidis bloodstream infection.
abstract: Unlike many localized infections, the development and resolution of bacteremia involves physical and immunological interactions between many anatomic sites. In an effort to better understand these interactions, we developed a computational model of bacteremia as a dynamical system fashioned after multicompartmental pharmacodynamic models, incorporating bacterial proliferation and clearance in the blood, liver, spleen, and lungs, and the transport of pathogens between these sites. A system of four first-order homogeneous ODEs was developed. Blood and organ bacterial burdens were measured at various time points from 3 to 48 h postinoculation using an LD25 murine model of Staphylococcus epidermidis bacteremia. Using these empiric data, solutions to the mathematical model were recovered. A bootstrap resampling method was used to generate 95% confidence intervals around the solved parameters. The validity of the model was examined in parallel experiments using animals acutely immunocompromised with cyclophosphamide; the model captured abnormalities in bacterial partitioning previously described with this antineoplastic agent. Lastly, the approach was used to explore possible benefits to clinically observed hyperdynamic blood flow during sepsis: in simulation, normal mice, but not those treated with cyclophosphamide, enjoyed significantly more rapid bacterial clearance from the bloodstream under hyperdynamic conditions.
authors.affiliation: Department of Emergency Medicine and Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Hangyul M
authors.initials: HM
authors.lastname: Chung
authors.forename: Megan M
authors.initials: MM
authors.lastname: Cartwright
authors.forename: David M
authors.initials: DM
authors.lastname: Bortz
authors.forename: Trachette L
authors.initials: TL
authors.lastname: Jackson
authors.forename: John G
authors.initials: JG
authors.lastname: Younger
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology* / Q000503:physiopathology; D003520:Cyclophosphamide / Q000494:pharmacology; D051379:Mice; D008962:Models, Theoretical; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D003520:Cyclophosphamide