Amphotericin B Delivery From Bone Cement Increases With Porosity but Strength Decreases

Kweon, Chris; McLaren, A. C.; Leon, Christine; McLemore, Ryan

doi:10.1007/s11999-011-1928-5

Cited by 54 publications

(45 citation statements)

References 19 publications

(42 reference statements)

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“…Of the published studies that report release data on antifungals [6,9,[14][15][16], two report voriconazole release data [6,14] ( Table 1). Both studies report release of voriconazole but had important methodological and formulation differences from our study.…”

Section: Discussionmentioning

confidence: 99%

“…Sealy et al [15] report elution data on ALBC made with five antifungals; however, technical details in their methods prevent comparison with our data. Amphotericin B deoxycholate with the addition of 10 g poragen [9] elutes less than 1% of the antifungal dose. In recent data reported by our laboratory, 800 mg amphotericin B deoxycholate also had low release but liposomal amphotericin B had higher release (11% of dose at 200 mg, 18% of dose at 800 mg).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Miller

McLaren

Pauken

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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“…Kweon et al 43 did a study to compare adding 200 mg amphotericin B to cement (Simplex P) versus adding a high dose poragen (10 g cefazolin) to increase release. They found that the release was increased in the batch with poragen, but it decreased compressive strength significantly.…”

Section: Cement Spacer With or Without Antifungals?mentioning

confidence: 99%

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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“…In an effort to determine the important parameters for effective local delivery, many authors have studied antimicrobial elution in vitro [8,18,19]. Elution studies evaluate the delivery vehicle's maximum capability to release antimicrobial, often inappropriately comparing eluant concentrations to the minimum inhibitory concentration (MIC) of target organisms.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Distribution From Local Delivery Depends on Dose

McLaren

Giers

Fraser

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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Background Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement. Questions/purposes We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery.

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Amphotericin B Delivery From Bone Cement Increases With Porosity but Strength Decreases

Abstract: Amphotericin B is released in very small amounts from antifungal-loaded bone cement. Release can be increased by adding high-dose poragen, but compressive strength decreases sufficiently to limit its use for implant fixation.

Cited by 54 publications

References 19 publications

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

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

Antimicrobial Distribution From Local Delivery Depends on Dose

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