Inhibition of Staphylococcus aureus biofilms by a novel antibacterial envelope for use with implantable cardiac devices

Abstract

Biofilm formation on representative implantable medical devices using a known human pathogen (Staphylococcus aureus) was significantly reduced (p < 0.01) at all time points measured (24,48, and 72 hours) by employing a novel antibacterial envelope (AIGIS Rx). The result was demonstrated using a standard US Centers for Disease Control (CDC) bioreactor model and the results were confirmed by Scanning Electron Microscopy (SEM). The antibacterial envelope used in the study is coated with a proprietary combination broad spectrum antibiotics (rifampin and minocycline) embedded in a resorbable polymeric coating. The antibiotics are designed to elute out of the coating over a multi-day period for controlled, site-specific drug delivery. The infection rate for patients receiving pacemakers and defibrillators is increasing faster than the rate of new implants and the growing resistance of S. aureus strains suggests that conventional, systemic antibiotic prophylaxis may have limited future utility. Moreover, emerging evidence suggests that bacterial biofilms result in infections of implantable medical devices. These findings demonstrate the in vitro efficacy of a new means to address potential biofilm-derived Hospital Acquired Infections (HAIs) related to implantable medical devices composed of titanium inclusive of pacemakers and defibrillators by means of a locally delivered, low dose, combination antibacterial treatment.

Figure 1

Schematic rendering of the CDC‐BR, model 90.

Figure 2

SEM micrographs at different magnifi cations of S. aureus biofilm formation on an exposed titanium coupon from a control reactor after 72 hours of incubation at room temperature. (A) 500x; (B) 9,000x.

Figure 3

Numbers of bacteria associated with experimental (AIGISRx™) and control envelopes after 72 hours at room temperature. 111 control and experimental envelopes were removed from the reactors after 72 hours of incubation at room temperature and processed as described in the “Methods” section to create bacterial suspensions and determine the number of bacteria associated with each envelope. The numbers of viable bacteria associated with the control and experimental envelopes are expressed as log₁₀ CFU/envelope.

Figure 4

Number of bacteria associated with enclosed and unenclosed titanium coupons from experimental and control reactors. Titanium coupons were removed from the reactors ater 72 hours of incubation at room temperature and processed as described in the “Methods” section to create bacterial suspensions and determine the number of bacteria associated with the titanium coupons. The numbers of viable bacteria associated with the control and experimental coupons are expressed as log₁₀ CFU/cm². CE = control/enveloped coupons; EE = experimental/enveloped coupons; CU = control/unenveloped (exposed) coupons; EU = experimental/unenveloped (exposed) coupons.

Figure 5

Number of bacteria in control and experimental reactor fluids after 24,48, and 72 hours at room temperature. Fluids from the control and experimental reactors were removed after 24, 48, and 72 hours of incubation at room temperature and the number of viable bacteria in the samples was determined. The numbers of viable bacteria found in the control and experimental reactor fluids are expressed as log₁₀ CFU/mL.

Figure 6

Differences in bacterial growth (turbidity) in experimental and control reactors after 72 hours of incubation at room temperature.

Figure 7

S. aureus biofilm formation on control and experimental envelopes at different magnifications after 72 hours of incubation at room temperature. (A) Control, 500x; (B) Control, 1,500x; (C) Experimental, 500x; (D) Experimental, 1,500x.

Figure 8

Representative biofilm formation at 7 days on pacemakers with or without the AIGISRx™ envelope after implantation in a rabbit model of infectivity using Acinetobacter baumanii. Left: with AIGISRx™ envelope; right: without AIGISRx™ envelope (Hansen et al. ³³ by permission).