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Voriconazole Admixed with PMMA—Impact on Mechanical Properties and Efficacy

Background: There are currently no recommendations to direct the optimal diagnosis and treatment of fungal osteoarticular infections, including prosthetic joint infections and osteomyelitis. Active agents (fluconazole; amphotericin B) are regularly applied per os or intravenously. Other drugs such as voriconazole are used less frequently, especially locally. Voriconazole is less toxic and has promising results. Local antifungal medication during primary surgical treatment has been investigated by implanting an impregnated PMMA cement spacer using intra-articular powder or by daily intra-articular lavage. The admixed dosages are rarely based on characteristic values and microbiological and mechanical data. The purpose of this in vitro study is to investigate the mechanical stability and efficacy of antifungal-admixed PMMA with admixed voriconazole at low and high concentrations. Methods: Mechanical properties (ISO 5833 and DIN 53435) as well as efficacy with inhibition zone tests with two Candida spp. were investigated. We tested three separate cement bodies at each measuring time (n = 3) Results: Mixing high dosages of voriconazole causes white specks on inhomogeneous cement surfaces. ISO compression, ISO bending, and DIN impact were significantly reduced, and ISO bending modulus increased. There was a high efficacy against C. albicans with low and high voriconazole concentrations. Against C. glabrata, a high concentration of voriconazole was significantly more efficient than a dose at a low concentration. Conclusions: Mixing voriconazole powder with PMMA (Polymethylmethacrylate) powder homogeneously is not easy because of the high amount of dry voriconazole in the powder formulation. Adding voriconazole (a powder for infusion solutions) has a high impact on its mechanical properties. Efficacy is already good at low concentrations.


The study explores the impact of mixing the antifungal agent voriconazole with polymethylmethacrylate (PMMA) bone cement, which is commonly used in joint surgeries. Fungal periprosthetic joint infections (FPJIs) are infrequent but challenging complications, often affecting patients with weakened immunity. The study aims to determine the mechanical stability of bone cement when combined with voriconazole and assess the inhibitory effect of voriconazole on Candida albicans and Candida glabrata.

The results indicate that the addition of voriconazole, especially in high dosages, affects the mechanical properties of PMMA. While the compressive strength meets industry standards, the bending strength is significantly reduced, falling below the recommended limit. The bending modulus increases with higher voriconazole concentrations. Impact strength is notably diminished with both low and high voriconazole doses.

In inhibition zone tests, voriconazole shows effectiveness against Candida albicans over a six-week period, with higher concentrations exhibiting better efficacy up to day 15. However, its efficacy against Candida glabrata is weaker, especially with low voriconazole concentrations.

The study concludes that the mechanical stability of PMMA is compromised when voriconazole is added, with variations in different mechanical properties.

Level of Evidence: As in in vitro study, level of evidence is low

Krampitz B, Steiner J, Trampuz A, Kühn KD. Voriconazole Admixed with PMMA—Impact on Mechanical Properties and Efficacy. Antibiotics. 2023;12(5):848.