A Novel Porous Antimicrobial Space Maintainer Eluting Econazole Has Activity against Candida and Aspergillus

A. M. Tatara1 , A. J. Salter1 , P. D. Kontoyiannis1 , E. Watson1 , N. D. Albert2 , G. R. Bennett1 , A. G. Mikos1

Author address: 

1 Rice Univ., Houston, TX, 2 The Univ. of Texas MD Anderson Cancer, Houston, TX

Abstract: 

Background: While relatively rare, fungal periprosthetic joint infections (FPJIs), most commonly caused by Candida and Aspergillus species, result in significant patient morbidity and mortality. Current therapy involves replacing the infected prosthesis with a polymethylmethacrylate (PMMA) spacer impregnated with antifungals for local release and infection clearance. However, these solid spacers have limited drug elution concentration and release duration. Therefore, we have designed a new type of porous spacer capable of extending the local release of therapeutics.Methods: Porous spacers made of PMMA and a non-toxic aqueous gel composed of carboxymethylcellulose (CMC) were fabricated as described previously[1]. These porous spacers were loaded with either 2.5% or 5% wt/wt econazole and compared to traditional non-porous econazole-loaded spacers. Cylinders of 6mm in diameter and 12mm in height (n=4 per group) were subject to mechanical analysis per established standards (ISO5833). Spacer discs of 6mm in diameter and 1mm in height were tested in a modified Kirby-Bauer disc diffusion assay (n=3 per group per organism) against clinical isolates of C. albicans and A. fumigatus.Results: Introduction of econazole at either loading dosage did not significantly reduce spacer mechanical properties in either porous or solid spacers. Introducing porosity significantly reduced spacer mechanical properties (offset yield strength and compressive modulus)- however, the properties of the porous spacers still remained sufficient for the demands of space maintenance of the joint[2]. Compared to solid econazole-loaded spacers, porous econazole-loaded spacers in the 5 wt/wt% loading dosage group created a significantly larger zone of inhibition against C. albicans and A. fumigatus. Unloaded spacers of either type produced no zone of inhibition.Conclusions: This new type of spacer can mitigate the growth of the most common fungal pathogens responsible for FPJIs while preserving sufficient mechanical properties for maintaining space in the joint. By incorporating porosity into the design of the spacer, we have demonstrated significantly increased inhibition of fungal species compared to the solid spacers currently used in clinical practice.
2016

abstract No: 

016

Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)