Publications

Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms

Mariël Miller, Jeffery C. Rogers, Marissa A. Badham, Lousili Cadenas, Eian Brightwell, Jacob Adams, Cole Tyler, Paul R. Sebahar, Travis J. Haussener, Hariprassada K. Reddy, Ryan E. Looper, Dustin L. Williams
bioRxiv 2020.06.04.133934; doi: https://doi.org/10.1101/2020.06.04.133934

Abstract
Biofilm-impaired tissue is a significant factor in chronic wounds such as diabetic foot ulcers. Most, if not all, anti-biotics in clinical use have been optimized against planktonic phenotypes. In this study, an in vitro assessment was performed to determine the potential efficacy of a unique first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. In the first method, biofilms were grown on cellulose discs on an agar surface. Topical agents were spread on gauze and placed over the biofilms for 24 h. Biofilms were quantified and imaged with confocal and scanning electron microscopy. In the second method, biofilms were grown on bioabsorbable collagen coupons in a modified CDC biofilm reactor. Coupons were immersed in treatment for 24 h. The first method was limited in its ability to assess efficacy. Efficacy profiles against biofilms grown on collagen were more definitive, with CZ-01179 gel eradicating well-established biofilms to a greater degree compared to clinical standards. In conclusion, CZ-01179 may be a promising topical agent that targets the biofilm phenotype. Pre-clinical work is currently being performed to determine the translatable potential of CZ-01179 gel.

Histological Analysis of a Retrieved Porous Tantalum Total Ankle Replacement: A Case Report

Epperson RT, Barg A, Williams DL, Saltzman CL.
JBJS Case Connect. 2020 Jan-Mar;10(1):e0379. doi: 10.2106/JBJS.CC.19.00379.
PMID: 32224645

Abstract
Case: We present a case report documenting the retrieval and histological analysis of a porous tantalum (P-Ta) total ankle replacement (TAR) from a 50-year-old woman after a below-knee transtibial amputation. This rare opportunity to examine an intact TAR may help to better understand the implant-bone relationship because it would be in situ.

Conclusion: In this case study, we demonstrate bone ingrowth to the first layer of the P-Ta and organized trabecular orientation, suggesting that equal bone load was achieved on the base and the rails in both components using a transfibular surgical approach.

(Preprint) Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilm.

bioRxiv 2020.06.04.133934; doi: https://doi.org/10.1101/2020.06.04.133934

Histological Analysis of a Retrieved Porous Tantalum Total Ankle Replacement: A Case Report.

Epperson RT, Barg A, Williams DL, Saltzman CL.

JBJS Case Connect. 2020 Jan-Mar;10(1):e0379. doi: 10.2106/JBJS.CC.19.00379.PMID: 32224645

Assessing the effect of physeal biopsy on angular deformity in a rabbit model.

Stevens P, Epperson RT, Taylor NB, Dickerson M, Williams DL.

J Pediatr Orthop B. 2019 Oct 22. doi: 10.1097/BPB.0000000000000687. PMID: 31651751

Plume height and surface coverage analysis of methicillin-resistant Staphylococcus aureus isolates grown in a CDC biofilm reactor.

Rasmussen RM, Epperson RT, Taylor NB, Williams DL.

Biofouling. 2019 Apr;35(4):463-471. doi: 10.1080/08927014.2019.1612381. Epub 2019 May 30.PMID: 31144524

Growth substrate may influence biofilm susceptibility to antibiotics.

Williams DL, Smith SR, Peterson BR, Allyn G, Cadenas L, Epperson RT, Looper RE.

PLoS One. 2019 Mar 14;14(3):e0206774. doi: 10.1371/journal.pone.0206774. eCollection 2019.PMID: 30870411

System Setup to Deliver Air Impact Forces to a Sheep Limb: Preparation for Model Development of Blast-Related Heterotopic Ossification.

Williams DL, Epperson RT, Taylor NB, Nielsen MB, Kawaguchi BS, Rothberg DL, Pasquina PF, Isaacson BM.

JMIR Res Protoc. 2019 Feb 22;8(2):e12107. doi: 10.2196/12107.PMID: 30794203

In vitro testing of a first-in-class tri-alkylnorspermidine-biaryl antibiotic in an anti-biofilm silicone coating.

Ashton NN, Allyn G, Porter ST, Haussener TJ, Sebahar PR, Looper RE, Williams DL.

Acta Biomater. 2019 Jul 15;93:25-35. doi: 10.1016/j.actbio.2019.02.010. Epub 2019 Feb 12.PMID: 30769135

In vivo analysis of a first-in-class tri-alkyl norspermidine-biaryl antibiotic in an active release coating to reduce the risk of implant-related infection.

Williams DL, Epperson RT, Ashton NN, Taylor NB, Kawaguchi B, Olsen RE, Haussener TJ, Sebahar PR, Allyn G, Looper RE.

Acta Biomater. 2019 Jul 15;93:36-49. doi: 10.1016/j.actbio.2019.01.055. Epub 2019 Jan 31.PMID: 30710710

Ability of a wash regimen to remove biofilm from the exposed surface of materials used in osseointegrated implants.

Allyn G, Bloebaum RD, Epperson RT, Nielsen MB, Dodd KA, Williams DL.

J Orthop Res. 2019 Jan;37(1):248-257. doi: 10.1002/jor.24161. Epub 2018 Nov 19.PMID: 30341934

Revisiting the Anterior Glenoid: An Analysis of the Calcified Cartilage Layer, Capsulolabral Complex, and Glenoid Bone Density.

Karns MR, Epperson RT, Baran S, Nielsen MB, Taylor NB, Burks RT.

Arthroscopy. 2018 Aug;34(8):2309-2318. doi: 10.1016/j.arthro.2018.03.017. Epub 2018 Jul 7.PMID: 30078426

Flash autoclave settings may influence eradication but not presence of well-established biofilms on orthopaedic implant material.

Williams DL, Taylor NB, Epperson RT, Rothberg DL.

J Orthop Res. 2018 May;36(5):1543-1550. doi: 10.1002/jor.23764. Epub 2017 Nov 22.PMID: 28976597

Effect of silver-loaded PMMA on Streptococcus mutans in a drip flow reactor.

Williams DL, Epperson RT, DeGrauw JP, Nielsen MB, Taylor NB, Jolley RD.

J Biomed Mater Res A. 2017 Sep;105(9):2632-2639. doi: 10.1002/jbm.a.36112. Epub 2017 Jun 27.PMID: 28512783

Sustained tobramycin release from polyphosphate double network hydrogels.

Lane DD, Fessler AK, Goo S, Williams DL, Stewart RJ.

Acta Biomater. 2017 Mar 1;50:484-492. doi: 10.1016/j.actbio.2016.12.030. Epub 2016 Dec 18.PMID: 27993638

Transcortical or intracondylar? Which model is accurate for predicting biomaterial attachment in total joint replacement?

Bloebaum RD, Abdo NT, Hofmann AA, Epperson RT, Olsen RE, Chalayon O.

J Biomed Mater Res B Appl Biomater. 2018 Feb;106(2):578-588. doi: 10.1002/jbm.b.33873. Epub 2017 Feb 28.PMID: 28244245

Link Between Clinical Predictors of Heterotopic Ossification and Histological Analysis in Combat-Injured Service Members.

Isaacson BM, Potter BK, Bloebaum RD, Epperson RT, Kawaguchi BS, Swanson TM, Pasquina PF.

J Bone Joint Surg Am. 2016 Apr 20;98(8):647-57. doi: 10.2106/JBJS.15.00895.PMID: 27098323

Determining the Mineral Apposition Rate of Heterotopic Ossification in Military Healthcare System Patients after Total Joint Replacement: A Case Series.

Isaacson, B.M., B.K. Potter, R.D. Bloebaum, R.T. Epperson, B. Kawaguchi, T.M. Swanson, and P.F. Pasquina.

Bone and Tissue Regeneration Insights, (January 2016). doi:10.4137/BTRI.S38041.

Does vitamin E-blended UHMWPE prevent biofilm formation?

Williams DL, Vinciguerra J, Lerdahl JM, Bloebaum RD.

Clin Orthop Relat Res. 2015 Mar;473(3):928-35. doi: 10.1007/s11999-014-3673-z.PMID: 24832828

In vitro efficacy of a novel active-release antimicrobial coating to eradicate biofilms of Pseudomonas aeruginosa.

Williams DL, Lerdahl JM, Haymond BS, Bloebaum RD.

Antimicrob Agents Chemother. 2014;58(4):2400-4. doi: 10.1128/AAC.01798-13. Epub 2014 Jan 6.PMID: 24395238

Model development for determining the efficacy of a combination coating for the prevention of perioperative device related infections: a pilot study.

Sinclair KD, Pham TX, Williams DL, Farnsworth RW, Loc-Carrillo CM, Bloebaum RD.

J Biomed Mater Res B Appl Biomater. 2013 Oct;101(7):1143-53. doi: 10.1002/jbm.b.32924. Epub 2013 Apr 6.PMID: 23564717

The significance of calcified fibrocartilage on the cortical endplate of the translational sheep spine model.

Sinclair SK, Bell S, Epperson RT, Bloebaum RD.

Anat Rec (Hoboken). 2013 May;296(5):736-44. doi: 10.1002/ar.22683. Epub 2013 Mar 12.PMID: 23494918

Characterization of a novel active release coating to prevent biofilm implant-related infections.

Williams DL, Sinclair KD, Jeyapalina S, Bloebaum RD.

J Biomed Mater Res B Appl Biomater. 2013 Aug;101(6):1078-89. doi: 10.1002/jbm.b.32918. Epub 2013 Apr 4.PMID: 23559470

In vivo efficacy of a silicone‒cationic steroid antimicrobial coating to prevent implant-related infection.

Williams DL, Haymond BS, Beck JP, Savage PB, Chaudhary V, Epperson RT, Kawaguchi B, Bloebaum RD.

Biomaterials. 2012 Nov;33(33):8641-56. doi: 10.1016/j.biomaterials.2012.08.003. Epub 2012 Aug 30.PMID: 22940221

Development of a broad spectrum polymer-released antimicrobial coating for the prevention of resistant strain bacterial infections.

Sinclair KD, Pham TX, Farnsworth RW, Williams DL, Loc-Carrillo C, Horne LA, Ingebretsen SH, Bloebaum RD.

J Biomed Mater Res A. 2012 Oct;100(10):2732-8. doi: 10.1002/jbm.a.34209. Epub 2012 May 24.PMID: 22623404

Experimental model of biofilm implant-related osteomyelitis to test combination biomaterials using biofilms as initial inocula.

Williams DL, Haymond BS, Woodbury KL, Beck JP, Moore DE, Epperson RT, Bloebaum RD.

J Biomed Mater Res A. 2012 Jul;100(7):1888-900. doi: 10.1002/jbm.a.34123. Epub 2012 Apr 10.PMID: 22492534

Host bone response to polyetheretherketone versus porous tantalum implants for cervical spinal fusion in a goat model.

Sinclair SK, Konz GJ, Dawson JM, Epperson RT, Bloebaum RD.

Spine (Phila Pa 1976). 2012 May 1;37(10):E571-80. doi: 10.1097/BRS.0b013e318240f981.PMID: 22146277

Efficacy of a porous-structured titanium subdermal barrier for preventing infection in percutaneous osseointegrated prostheses.

Jeyapalina S, Beck JP, Bachus KN, Williams DL, Bloebaum RD.

J Orthop Res. 2012 Aug;30(8):1304-11. doi: 10.1002/jor.22081. Epub 2012 Jan 31.PMID: 22294380

Using biofilms as initial inocula in animal models of biofilm-related infections.

Williams DL, Costerton JW.

J Biomed Mater Res B Appl Biomater. 2012 May;100(4):1163-9. doi: 10.1002/jbm.b.31979. Epub 2011 Nov 28.PMID: 22120924

A modified CDC biofilm reactor to produce mature biofilms on the surface of peek membranes for an in vivo animal model application.

Williams DL, Woodbury KL, Haymond BS, Parker AE, Bloebaum RD.

Curr Microbiol. 2011 Jun;62(6):1657-63. doi: 10.1007/s00284-011-9908-2. Epub 2011 Mar 25.PMID: 21437591

Characterization of bacterial isolates collected from a sheep model of osseointegration.

Williams DL, Bloebaum RD, Beck JP, Petti CA.

Curr Microbiol. 2010 Dec;61(6):574-83. doi: 10.1007/s00284-010-9655-9. Epub 2010 May 11.PMID: 20458482

Observing the biofilm matrix of Staphylococcus epidermidis ATCC 35984 grown using the CDC biofilm reactor.

Williams DL, Bloebaum RD.

Microsc Microanal. 2010 Apr;16(2):143-52. doi: 10.1017/S143192760999136X. Epub 2010 Mar 8.PMID: 20205969

Assessing peri-implant tissue infection prevention in a percutaneous model.

Perry EL, Beck JP, Williams DL, Bloebaum RD.

J Biomed Mater Res B Appl Biomater. 2010 Feb;92(2):397-408. doi: 10.1002/jbm.b.31528.PMID: 19927331

Protein phosphorylation in irradiated human melanoma cells.

Warters RL, Williams DL, Zhuplatov SB, Pond CD, Leachman SA.

Radiat Res. 2007 Nov;168(5):535-44. doi: 10.1667/RR0404.1.PMID: 17973544

Deparaffinizing Soft–Tissue Sections for Elemental Analysis of Wear Particulate

Koller, K.E., Epperson, R.T., & Bloebaum, R.D.

Journal of Histotechnology (2006). 29, 233 - 235.

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