Local Antibiotic Therapy in the Treatment of Bone and Soft Tissue Infections

Tsourvakas, Stefanos

doi:10.5772/28833

Cited by 22 publications

(22 citation statements)

References 111 publications

(98 reference statements)

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“…This can lead to unwanted side effects and systemic toxicity as well as further pathogenic resistance. 6 An alternative modality is local delivery of antibiotics through controlled release from beads implanted to fill dead space. 3 This enables levels of local concentration that can be many times the minimum bactericidal concentration (MBC) for the infecting pathogens, while at the same time the risk of high systemic levels and associated toxicity remain low.…”

Section: Introductionmentioning

confidence: 99%

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

McConoughey

Howlin

Wiseman

et al. 2014

J. Biomed. Mater. Res.

102

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Antibiotic-loaded bone cement is a primary option for treatment of orthopedic infections. Poly(methyl methacrylate) (PMMA) is a widely used cement that, when loaded with antibiotics in spacer or bead form, has been shown to reduce infection rates. However, PMMA is not resorbable and requires a second surgery for removal, while also acting as a potential foreign body for bacterial colonization. Alternatively, resorbable bone cements, such as calcium sulfate, have been proposed and present the advantage of being completely reabsorbed. It is unknown whether the antibiotic elution characteristics of absorbable bone cements are similar to PMMA. This study (1) characterized antibiotic elution from synthetic, highly purified calcium sulfate cement beads of varying sizes against pathogenic bacteria both in liquid culture and seeded on agar plates, (2) tested calcium sulfate beads against PMMA beads loaded with the same antibiotics, and (3) analyzed the structural differences between how PMMA and calcium sulfate bind to antibiotics. In every assay, the calcium sulfate beads performed as well as, or better than, the PMMA beads in inhibition of bacterial growth and elution of vancomycin in vitro with complete elution observed from calcium sulfate within three days. These data suggest that calcium sulfate, functions, as well as PMMA in the patient setting for infection control.

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Section: Introductionmentioning

confidence: 99%

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

McConoughey

Howlin

Wiseman

et al. 2014

J. Biomed. Mater. Res.

102

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“…On top of limiting the efficacy of the treatment, this can increase the risk of generating antibioticresistance [9]. Different methods can be used to overcome these limitations.…”

Section: Introductionmentioning

confidence: 99%

Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity–drug interaction

2015

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Please cite this article as: Pastorino, D., Canal, C., Ginebra, M-P., Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity-drug interaction, Acta Biomaterialia (2014), doi: http://dx.doi.org/10. 1016/ j.actbio.2014.10.031 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractIn this work novel injectable Calcium Phosphate Foams (CPFs) were combined with an antibiotic (Doxycycline) to design an innovative dosage form for bone regeneration.The material structure, its drug release profile and antibiotic activity were investigated, while its clinical applicability was assessed through cohesion and injectability tests.Doxycycline had a clear effect on both the micro-and macro-structure of the CPFs due to its role as nucleating agent of hydroxyapatite and a drying effect on the paste. Doxycycline-loaded CPFs presented interconnected macroporosity, which increased drug availability as compared to Calcium Phosphate Cements, and was a critical parameter controlling the release kinetics, which followed a non-Fickian diffusion model. Up to 55% (1 mg) of the drug was released progressively in 5 days, the percentage released being proportional to the macroporosity of the CPFs. All Doxycycline-containing foams had immediate cohesion and were injectable. Moreover, antibacterial activity was observed against Staphylococcus Aureus and Escherichia Coli. Thus, in addition to enhancing osteoconduction and material resorption, macroporosity allows tuning the local delivery of drugs from injectable calcium phosphates.

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“…[16][17][18] While effective, the disadvantages of currently used non-biodegradable polymethyl-methacrylate beads include low biocompatibility, poor antibiotic release, need for surgical removal, and cytotoxic effects due to thermal damage during polymethyl-methacrylate polymerization. [17][18][19][20] A biodegradable antibiotic carrier would offer many advantages. There is no need for secondary surgery, and biodegradable carriers are gradually replaced by ingrowing tissue and may even support new bone growth.…”

Section: Introductionmentioning

confidence: 99%

Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications

Weisman¹,

Nicholson²,

Tappa³

et al. 2015

IJN

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Three-dimensional (3D) printing and additive manufacturing holds potential for highly personalized medicine, and its introduction into clinical medicine will have many implications for patient care. This paper demonstrates the first application of 3D printing as a method for the potential sustained delivery of antibiotic and chemotherapeutic drugs from constructs for patient treatment. Our design is focused on the on-demand production of anti-infective and chemotherapeutic filaments that can be used to create discs, beads, catheters, or any medical construct using a 3D printing system. The design parameters for this project were to create a system that could be modularly loaded with bioactive agents. All 3D-printed constructs were loaded with either gentamicin or methotrexate and were optimized for efficient and extended antibacterial and cancer growth-inhibiting cytostatic activity. Preliminary results demonstrate that combining gentamicin and methotrexate with polylactic acid forms a composite possessing a superior combination of strength, versatility, and enhanced drug delivery. Antibacterial effects and a reduction in proliferation of osteosarcoma cells were observed with all constructs, attesting to the technical and clinical viability of our composites. In this study, 3D constructs were loaded with gentamicin and methotrexate, but the method can be extended to many other drugs. This method could permit clinicians to provide customized and tailored treatment that allows patient-specific treatment of disease and has significant potential for use as a tunable drug delivery system with sustained-release capacity for an array of biomedical applications.

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Local Antibiotic Therapy in the Treatment of Bone and Soft Tissue Infections

Cited by 22 publications

References 111 publications

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity–drug interaction

Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications

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