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

EmmaK. Knapp¹  KarenL. de Mesy Bentley¹  StephenL. Kates¹  MarkJ. Ninomiya¹  HaniA. Awad²  IhabM. El-Atawneh²  RyanP. Trombetta²  EdwardM. Schwarz²  PaulM. Dunman³ 

[1] Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA;Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA;Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA;

关键词: osteomyelitis;    Staphylococcus aureus;    sitafloxacin;    rifampin;    calcium phosphate;    3D printing;    drug delivery;    1-stage revision;    PMMA;   

DOI  :  10.3390/pharmaceutics11020094

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown