Implantable Device-Related Infection

Abstract

Over half of the nearly two million healthcare-associated infections can be attributed to indwelling medical devices. In this review, we highlight the difficulty in diagnosing implantable device-related infection and how this leads to a likely underestimate of the prevalence. We then provide a length-scale conceptualization of device-related infection pathogenesis. Within this conceptualization we focus specifically on biofilm formation and the role of host immune and coagulation systems. Using this framework, we describe how current and developing preventative strategies target specific processes along the entire length-scale. In light of the significant time horizon for the development and translation of new preventative technologies, we also emphasize the need for parallel development of in situ treatment strategies. Specific examples of both preventative and treatment strategies and how they align with the length-scale conceptualization are described.

Figure 1

Illustration of the length-scale conceptualization of the pathogenesis of implantable device related infection. (A) Surgical incision and wound creation leads to continuity between sterile and non-sterile compartments of the body as well as inflammatory reaction. (B) Extracellular fluids and blood cells in the wound come into contact with the abiotic implanted material initiating both inflammatory and coagulation cascades. (C) Host proteins (e.g., fibrin, thrombin, albumin) also interact with the surface as well as bacteria leading to the development of a biofilm. (D) At the nano and sub-nanometer scale the interaction of a cell or molecule with a surface is governed by basic physiochemical properties. A particle approaching the surface by bulk transport may have an opposite or similar charge as the surface leading to electrostatic attraction or repulsion. In an aqueous environment a double layer of water molecules will develop on the charge surface, further contributing to the energy of interaction. Van der Waals forces will provide additional attractive forces. Finally, biological particles will have receptor-ligand interactions which provide strong and sometimes irreversible attractive interaction.

Figure 2

Computational simulation of quorum sensing (QS). Bacteria were modeled as point sources of QS molecules. Those molecules were free to diffuse by simple Brownian motion. In the top we demonstrate the concentration of QS molecules surround two bacteria approaching each other. The plot shows the concentration of the QS molecules on the bacterial surface as a function of the separation distance. Note, that this is a computation simulation using dimensionless parameters, therefore there are no units. This demonstrates how a bacterium can sense the presence of a neighboring bacterium in close proximity. In the bottom a similar simulation demonstrates the concentration and distribution QS molecules as a bacterium approaches a wall. Again the QS concentration rapidly increases providing a signal to the bacterium.

Figure 3

Scanning electron micrographs of staphylococcal biofilms (A) grown in vitro on polystyrene culture pegs and (B) harvested from an infected ventriculoperitoneal shunt. Note the scant ECM on the in vitro biofilm in (A) and the bacteria adhered to dense fibrin clot matrix in (B).

Figure 4

Demonstration of specific preventative anti-infective strategies mapped onto the length-scale conceptualization of implantable device related infection. (A) Chlorhexidine sponge at the insertion site of a triple lumen central venous catheter to reduce transport of skin bacteria along the catheter to the bloodstream. (B) Dialysis catheters with different geometries can altered blood flow patterns which results in altered transport of cells or other materials to the catheter surface. (C) Polymer coatings with specific chemical end groups that prevent adhesion or have antibacterial properties upon contact. (D) Devices can be impregnated with antimicrobial substances that are eluted to kill bacteria in proximity to the device surface. (E) Nano-scale patterning of a surface can alter bacterial adhesion and proliferation.

Figure 5

Scanning electron micrograph of Staphylococcus aureus interacting with a nano-textured polyurethane surface.