Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Abstract

Background Local delivery of antifungals is an important modality in managing orthopaedic fungal infection. Voriconazole is a powder antifungal suitable for addition to bone cement that is released from bone cement but the mechanical properties of antimicrobial-loaded bone cement (ALBC) made with voriconazole are unknown. Questions/Purposes (1) Is voriconazole release dosedependent? (2) Is released voriconazole active? (3) Is the loss of ALBC's compressive strength caused by voriconazole dose-and elution-dependent? Methods Sixty standard test cylinders were fabricated with ALBC: 300 or 600 mg voriconazole per batch eluted for 30 days in deionized water. Voriconizole concentration in the eluate was measured using high-performance liquid chromatography. Cumulative-released voriconizole was calculated. Biologic activity was tested. Compressive strength was measured before and after elution. The effect of dose and time on release and compressive strength were analyzed using repeated-measure analysis of variance. Results Fifty-seven percent and 63% of the loaded voriconazole were released by Day 30 for the 300-mg and 600-mg formulations, respectively. The released voriconazole was active on bioassay. Compressive strength was reduced from 79 MPa to 53 MPa and 69 MPa to 31 MPa by 30 days for the 300-mg and 600-mg formulations, respectively. Conclusions Voriconazole release from ALBC increases with dose and is bioactive. Loss in compressive strength is greater after elution and with higher dose. Clinical Relevance Three hundred milligrams of voriconazole in ALBC would be expected to deliver meaningful amounts of active drug in vivo. The compressive strength of ALBC with 600 mg voriconazole is less than expected compared to commonly used antibacterials.

Trowels and Tribulations: Review of Antimicrobial‐Impregnated Bone Cements in Prosthetic Joint Surgery

“…It is also available in a lyophilized powder formulation. A modest and dose‐dependent voriconazole elution was observed over a period of 30 days at doses of 300 mg and 600 mg per 40 g PMMA cement . Notably, a 55% reduction in compressive strength was observed at the higher dose.…”

“…Voriconazole, a small (349 Da) but less hydrophilic azole antifungal, is also bioactive following polymerization . It is also available in a lyophilized powder formulation.…”

Liposomal Formulation Decreases Toxicity of Amphotericin B In Vitro and In Vivo

“…We have previously studied ALBC with amphotericin B deoxycholate [8], finding limited release and significant toxicity to fibroblasts and osteoblasts at relatively low concentrations [6]. We subsequently showed that both liposomal amphotericin B [4] and voriconazole [12] are delivered from ALBC in much greater amounts than amphotericin B deoxycholate. Liposomal amphotericin B is known to be less toxic than amphotericin B deoxycholate when delivered intravenously [2]; however, there are no reported data on the local toxicity from locally delivered liposomal amphotericin B.…”

Single-stage revision for fungal peri-prosthetic joint infection

“…There remains controversy regarding the elution properties of antifungal agents in bone cement, and the dose required in the treatment of deep fungal infections. [1][2][3] A major complication of the systemic use of antifungal agents is the risk of side effects. 4,5 Most authors recommend a two-stage procedure for the management of fungal PJI, with or without the use of a cement spacer.…”