In Vitro Activity of Calcium Sulfate and Hydroxyapatite Antifungal Disks Loaded with Amphotericin B or Voriconazole in Consideration for Adjunctive Osteomyelitis Management

Abstract

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.

Pulsed Laser Deposited Biocompatible Lithium-Doped Hydroxyapatite Coatings with Antimicrobial Activity

“…Last but not least, there are reports in the literature on the antibacterial potential of antibiotics/antibacterial substances-loaded HA, but very few refer to antifungal-loaded cement drug delivery [87]. We stress upon that there are even fewer reports dedicated to the antibacterial activity of lithium [88].…”

Eradication of Lomentospora prolificans Osteomyelitis of the Wrist with Combination Antifungal Therapy, Voriconazole Bone Cement, and Surgical Debridement

“…Osteomyelitis is a complex condition that requires a multidisciplinary approach between orthopaedics, infectious diseases, and plastics, as outlined in this case report [ 10 , 11 , 26 ]. The goal of therapy is to eradicate the infection and avoid soft tissue and functional loss, via a combination of surgical source control, antibiotic delivery, minimising joint and soft tissue dead space, and managing comorbidities [ 9 – 11 , 21 ]. However, in vitro studies on antifungal susceptibility of L. prolificans consistently show high minimum inhibitory concentrations (MIC) across all antifungal agents, including Azoles, Terbinafine, and Amphotericin B [ 1 , 12 , 15 ].…”

“…The technique of incorporating antibiotics into polymethylmethacrylate (PMMA) cement was first developed in 1970 by Buchholz and Engelbrecht [ 27 ] and has since been used in open fractures, osteomyelitis, and index and infected arthroplasty procedures [ 21 , 28 ]. The advantage of this modality is its ability to deliver antibiotics locally, at a concentration greater than the MIC required to treat the infection at its source, which may not be achievable via the parenteral route [ 9 , 29 ]. While there is the risk of local cytotoxicity and other adverse patient effects, the use of drug-eluting cement beads has minimal risk of systemic effects and does not depend on the vascularity of the target tissue [ 28 ].…”

“…Fungal osteomyelitis is an example of such a pernicious manifestation, which is often preceded by trauma that disrupts the anatomic barrier to allow the pathogen to inoculate the region in question [ 1 , 4 , 7 ]. The standard goal of therapy involves meticulous, yet aggressive, surgical source control and antibiotic treatment, utilising the best available guidelines, along with infectious disease specialist support; the minimisation of joint and soft tissue dead space and balanced, multidisciplinary management of often significant medical comorbidities, including diabetes, heart disease, and rheumatological conditions, form an important adjunct to these broad objectives [ 9 – 11 ]. While L. prolificans has intrinsic resistance to all available antifungal agents, including the Azoles, Terbinafine, and Amphotericin B, several case reports and in vitro studies have shown favourable outcomes with combination antifungal therapy, notably voriconazole with Terbinafine [ 1 , 8 , 12 – 20 ].…”

“…While L. prolificans has intrinsic resistance to all available antifungal agents, including the Azoles, Terbinafine, and Amphotericin B, several case reports and in vitro studies have shown favourable outcomes with combination antifungal therapy, notably voriconazole with Terbinafine [ 1 , 8 , 12 – 20 ]. Additionally, in vitro studies have also shown the potential benefits of using antifungal-loaded cement beads, which are made by the surgical team in theatre, as an adjunct to antifungal therapy, with case reports showing variable measures of success [ 9 , 21 – 23 ]. This case report describes L. prolificans osteomyelitis of the wrist and carpus in an immunocompromised adult male host, successfully treated with combination antifungal therapy, staged surgical debridement, and the use of intraoperatively made voriconazole-loaded cement beads.…”