Elution and Mechanical Properties of Antifungal Bone Cement

Goss, Ben; Lutton, Cameron; Weinrauch, Patrick C.; Jabur, Majid; Gillett, Greg; Crawford, Ross

doi:10.1016/j.arth.2006.09.013

Cited by 84 publications

(76 citation statements)

References 14 publications

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“…Various studies describe surgeon-directed antifungal formulations of antimicrobial-loaded bone cement (ALBC) [2,6,9,10,15,16]. Published data from amphotericin B studies establish limited release occurs, increased release using the liposome formulation, higher than expected compressive strength, possibly related to crosslinking with PMMA, and cytotoxicity at low concentrations [2,5,8,9]. However, clinical experience in a case report by Marra et al [10] suggests that sufficient amphotericin B is released in vivo to be measurable and clinically efficacious.…”

Section: Introductionmentioning

confidence: 99%

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Miller

McLaren

Pauken

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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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.

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Section: Introductionmentioning

confidence: 99%

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Miller

McLaren

Pauken

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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“…In accordance with this finding, Bruce et al reported two cases of fungal infection of prosthetic joints which were treated successfully with fluconazole-impregnated PMMA beads, surgical debridement, and oral fluconazole [2]. However, Goss et al measured the elution of amphotericin B from PMMA using ultraviolet-visible spectroscopy, and determined that less than 0.03% of the amphotericin B was released [3]. Sealy et al showed that anidulafungin levels in fetal calf serum surrounding PMMA spheres rapidly became undetectable, suggesting that anidulafungin may not be appropriate for incorporation in PMMA [7].…”

Section: Introductionmentioning

confidence: 79%

Are Anidulafungin or Voriconazole Released from Polymethylmethacrylate In Vitro?

Rouse

Heijink

Steckelberg

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Depot delivery of antimicrobial agents is used for treatment and prevention of bacterial orthopaedic infections; there is little information regarding newer antifungal agents and their potential use in polymethylmethacrylate (PMMA) depot delivery. Questions/purposes We determined the percent of anidulafungin or voriconazole present after polymerization in PMMA beads loaded with anidulafungin or voriconazole, and we assessed elution of anidulafungin or voriconazole from beads loaded with anidulafungin or voriconazole. Materials and Methods Beads containing 7.5% anidulafungin or voriconazole were pulverized and incubated in Kreb's ringer buffer for 48 hours; the buffer was assayed for anidulafungin or voriconazole concentration. The in vitro release of anidulafungin and voriconazole from PMMA beads loaded with 7.5% anidulafungin or voriconazole was determined in triplicate in a continuous flow chamber.Results 0.7% of anidulafungin and 5.6% of voriconazole loaded in the beads were detected after polymerization. No anidulafungin was detected in the elution studies. The mean peak voriconazole concentration in the elution studies was 0.9 lg/mL. Conclusions Anidulafungin may not be suitable for depot delivery in PMMA.

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“…3,5 Candida albicans is the most common organism. 6 Fungal infections are prone to biofilm formation which makes treatment difficult as the drugs available do not all have good biofilm penetration. Candida albicans especially produces a more complex biofilm which increases the antifungal resistance.…”

Section: Discussionmentioning

confidence: 99%

“…31,44,45 Studies differ with regards to amphotericin B release from cement. 6,31 Goss et al 6 found that adding more than 100 mg increases in the compressive strength by about 20%. They did not find any amphotericin B being released from the PMMA due to the chemical binding, thus increasing the strength.…”

Section: Cement Spacer With or Without Antifungals?mentioning

confidence: 99%

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Periprosthetic fungal infections: Be alert ( Clinical cases and review of the literature)

Botha¹,

Roux²,

McLoughlin³

2016

SA orthop. j.

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The increasing rate of arthroplasty, revisions and resistance to antibiotics has increased the risk for fungal infections. Fungal infections after joint replacements are rare but devastating. Different treatment modalities exist: suppressive therapy, debridement with retained prosthesis, Girdlestone procedures and 2-or even 3-stage revision arthroplasty. The aim of the review is to guide the surgeon with regard to a protocol to address fungal infections. AbstractThe increasing rate of arthroplasty, revisions and resistance to antibiotics has increased the risk for fungal infections. Different treatment modalities exist: suppressive therapy, debridement with retained prosthesis, Girdlestone procedures and 2-or even 3-stage revision arthroplasty. Fungal infections after joint replacements are rare but devastating. Purpose of the study:The aim was to see if there was any trend that could help with the diagnosis and management of patients with fungal infections. The literature was reviewed in order to assist with diagnosis and treatment. Materials and methods:A retrospective study was performed and all the cases seen and treated by a tumour and sepsis orthopaedic specialist from 1999 to 2015 were evaluated. Inclusion criteria: Patients had to be diagnosed with a fungal infection in any specimen which was sent for histology or culture. Exclusions: none.Results: Four patients were identified. All of them were males. Mean age 58 (35-71) years. The primary surgical indications were: vertebral osteomyelitis; post primary knee replacement; pig bite with lower limb sepsis and osteoarthritis knee, and a septic total hip replacement. Three cases cultured Candida parapsilosis and one Candida albicans of which three were tissue cultures and one a blood culture.Currently 75% have failed treatment -one passed away, one developed systemic sepsis, and one had an above-knee amputation and is still struggling with subsequent bacterial infections in the amputation stump. Conclusion:As long as there are higher incidences of fungal infections with devastating complications more evidence is needed. Numerous small case studies have been published, with the purpose of looking for the correct treatment: monotherapy, combination therapy, newer antifungals, higher dosages, implant retention or removal. It appears that the correct answer is unclear as yet.It is important to always have a high index of suspicion and good pre-operative planning together with a team approach: infectious diseases specialist, microbiologist and histologist. This approach will optimise the probability of making a diagnosis and to appropriately manage the fungus cultured.

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Elution and Mechanical Properties of Antifungal Bone Cement

Cited by 84 publications

References 14 publications

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Are Anidulafungin or Voriconazole Released from Polymethylmethacrylate In Vitro?

Periprosthetic fungal infections: Be alert ( Clinical cases and review of the literature)

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