In vitro activity of calcium sulfate and hydroxyapatite antifungal disks loaded with amphotericin B or voriconazole in consideration for adjunctive osteomyelitis management

J Am Podiatr Med Assoc. 2015 Mar;105(2):104-10. doi: 10.7547/0003-0538-105.2.104.

Abstract

Background: Regarding antibiotic-loaded cements, there is an abundant amount of literature regarding the antibacterial in vitro inhibitory and clinical applications for the treatment of osteomyelitis. The opposite can be said about literature regarding in vitro antifungal-loaded cement drug delivery for the treatment of fungal osteomyelitis.

Methods: Aspergillus fumigatus and Candida (ATCC 1023ATCC, Manassas, Virginia) were plated on antibiotic/antifungal-free plates. Voriconazole- and amphotericin B-impregnated calcium sulfate and hydroxyapatite (HA) disks, calcium sulfate + HA control disks, and control polymethylmethacrylate disks were laid separately onto plates separately inoculated with Aspergillus and Candida spp. The zones of inhibition obtained were measured in millimeters at 24, 36, and 96 hours.

Results: Etest (bioMérieux, Marcy l'Etoile, France) results demonstrated susceptibility of Aspergillus and Candida to amphotericin B and voriconazole. The zone of inhibition data demonstrated that voriconazole and amphotericin B retained their antifungal activity when mixed into the calcium sulfate + HA bone void filler and eluted at biologically effective antifungal concentrations over 96 hours.

Conclusions: The calcium sulfate + HA bone void filler is a biocompatible ceramic carrier vehicle that can successfully deliver the antifungal drugs voriconazole and amphotericin B in the adjunctive treatment of fungal osteomyelitis. It is a reliable strategy in the local delivery of antifungal drugs to an area of osteomyelitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / administration & dosage*
  • Antifungal Agents / administration & dosage
  • Aspergillosis / drug therapy*
  • Aspergillosis / microbiology
  • Aspergillosis / pathology
  • Aspergillus / drug effects
  • Aspergillus / isolation & purification*
  • Calcium Sulfate / pharmacology*
  • Cells, Cultured
  • Delayed-Action Preparations
  • Dental Materials / pharmacology
  • Humans
  • Hydroxyapatites / pharmacology*
  • Microbial Sensitivity Tests
  • Osteoblasts / drug effects
  • Osteoblasts / microbiology
  • Osteoblasts / pathology
  • Osteomyelitis / drug therapy*
  • Osteomyelitis / microbiology
  • Osteomyelitis / pathology
  • Voriconazole / administration & dosage*

Substances

  • Antifungal Agents
  • Delayed-Action Preparations
  • Dental Materials
  • Hydroxyapatites
  • hydroxyapatite cement
  • Amphotericin B
  • Voriconazole
  • Calcium Sulfate