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Article

Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis

1
Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA
2
Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA
3
Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA
4
Department of Pathology & Laboratory Medicine, University of Rochester, Rochester, NY 14642, USA
5
Department of Orthopedics, University of Rochester Medical Center, Rochester, NY 14642, USA
6
Department of Orthopaedic Surgery, Virginia Commonwealth University School of Medicine, Richmond, VA 0153, USA
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(2), 94; https://doi.org/10.3390/pharmaceutics11020094
Received: 16 January 2019 / Revised: 12 February 2019 / Accepted: 17 February 2019 / Published: 22 February 2019
(This article belongs to the Special Issue Bone Targeted Drug Delivery)
Osteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the PMMA cement as a drug release device. Hence, the objective of this study was to design and evaluate a bioresorbable calcium phosphate scaffold (CaPS) for sustained antimicrobial drug release and investigate its efficacy in a murine model of femoral implant-associated osteomyelitis. Incorporating rifampin and sitafloxacin, which are effective against bacterial phenotypes responsible for bacterial persistence, into 3D-printed CaPS coated with poly(lactic co-glycolic) acid, achieved controlled release for up to two weeks. Implantation into the murine infection model resulted in decreased bacterial colonization rates at 3- and 10-weeks post-revision for the 3D printed CaPS in comparison to gentamicin-laden PMMA. Furthermore, a significant increase in bone formation was observed for 3D printed CaPS incorporated with rifampin at 3 and 10 weeks. The results of this study demonstrate that osteoconductive 3D printed CaPS incorporated with antimicrobials demonstrate more efficacious bacterial colonization outcomes and bone growth in a single-stage revision in comparison to gentamicin-laden PMMA requiring a two-stage revision. View Full-Text
Keywords: osteomyelitis; Staphylococcus aureus; sitafloxacin; rifampin; calcium phosphate; 3D printing; drug delivery; 1-stage revision; PMMA osteomyelitis; Staphylococcus aureus; sitafloxacin; rifampin; calcium phosphate; 3D printing; drug delivery; 1-stage revision; PMMA
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MDPI and ACS Style

Trombetta, R.P.; Ninomiya, M.J.; El-Atawneh, I.M.; Knapp, E.K.; de Mesy Bentley, K.L.; Dunman, P.M.; Schwarz, E.M.; Kates, S.L.; Awad, H.A. Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis. Pharmaceutics 2019, 11, 94. https://doi.org/10.3390/pharmaceutics11020094

AMA Style

Trombetta RP, Ninomiya MJ, El-Atawneh IM, Knapp EK, de Mesy Bentley KL, Dunman PM, Schwarz EM, Kates SL, Awad HA. Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis. Pharmaceutics. 2019; 11(2):94. https://doi.org/10.3390/pharmaceutics11020094

Chicago/Turabian Style

Trombetta, Ryan P., Mark J. Ninomiya, Ihab M. El-Atawneh, Emma K. Knapp, Karen L. de Mesy Bentley, Paul M. Dunman, Edward M. Schwarz, Stephen L. Kates, and Hani A. Awad. 2019. "Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis" Pharmaceutics 11, no. 2: 94. https://doi.org/10.3390/pharmaceutics11020094

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