A MOUSE MODEL OF IMPLANT-ASSOCIATED INFECTION

Infections of implanted devices are of increasing frequency and import ance, representing a significant limitation of many therapeutic modali ties There are puzzling features of implant-associated infection inclu ding the changes in microbial flora, the tendency to chronicity and im paired responses to conservative modes of treatment. The concept of th e bacterial biofilm as a shielding mechanism generated by bacteria adh erent to artificial surfaces has recently been proposed as an explanat ion for these features. The biofilm is a term applied to a complex com prising the implant surface, adherent bacteria and a specialized matri x enclosing the bacteria. The matrix of the biofilm is an electrostati cally charged glue-like extracellular polymer derived by bacterial enz ymes acting on tissue carbohydrates, formed by bacteria when adherent to surfaces. This matrix binds the bacteria to the surface providing a sequestration affording selective protection against harmful elements of the environment, especially mechanisms of host defenses and antimi crobial agents. These biological systems are complex to study because of the dynamic interaction of the microbial variables, host defenses, properties of synthetic materials and the biofilm matrix itself There is a need for a laboratory model in which the variables can be control led permitting the researcher to examine the outcomes of modifying one variable at a time in a planned and orderly manner. The practical way to attain this end is the conduct of studies in a stable reproducible animal model of localized biofilm-implant infection. Staphylococcus e pidermidis is a representative of the Glass of microorganisms predomin ant in implant-associated infection. This paper describes the developm ent of a model utilizing an implant-S. epidermidis-biofilm infection l ocalized to the peritoneal cavity of the mouse. The natural history of the infection has been well documented and is stable in all respects for periods exceeding 3 months. This chronicity is especially advantag eous in analyzing the impact of long-term therapeutic modalities and n ecessary periods of recovery and assessment. A representative example of an experimental use of this model to determine the relative efficac y of antibiotic therapeutic regimes is described, demonstrating ifs sc ope and efficacy.