دورية أكاديمية
أعرض في EDS

Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S. aureus infection with osseointegration in murine models of implant-associated osteomyelitis.

التفاصيل البيبلوغرافية
العنوان: Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S. aureus infection with osseointegration in murine models of implant-associated osteomyelitis.
المؤلفون: Ren Y; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., Weeks J; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., Xue T; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., Rainbolt J; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., de Mesy Bentley KL; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Pathology and Center for Advanced Research Technologies, University of Rochester Medical Center, Rochester, NY, 14642, USA., Shu Y; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., Liu Y; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., Masters E; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., Cherian P; BioVinc, LLC, Pasadena, CA, 91107, USA., McKenna CE; Department of Chemistry, University of Southern California, Los Angeles, CA, 90089, USA., Neighbors J; Department of Pharmacology, Pennsylvania State University, Hershey, PA, 17033, USA., Ebetino FH; BioVinc, LLC, Pasadena, CA, 91107, USA.; Department of Chemistry, University of Rochester, Rochester, NY, 14642, USA., Schwarz EM; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA., Sun S; BioVinc, LLC, Pasadena, CA, 91107, USA. shuting.sun@biovinc.com., Xie C; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, 14642, USA. chao_xie@urmc.rochester.edu.; Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY, 14642, USA. chao_xie@urmc.rochester.edu.
المصدر: Bone research [Bone Res] 2023 Oct 18; Vol. 11 (1), pp. 51. Date of Electronic Publication: 2023 Oct 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: West China School of Stomatology, Sichuan University Country of Publication: China NLM ID: 101608652 Publication Model: Electronic Cited Medium: Print ISSN: 2095-4700 (Print) Linking ISSN: 20954700 NLM ISO Abbreviation: Bone Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 2014- : Chengdu, Sichuan, P. R. China : [New York] : West China School of Stomatology, Sichuan University ; co-published by Nature Publishing Group
Original Publication: Chengdu, Sichuan, P. R. China : Sichuan University Press
مواضيع طبية MeSH: Methicillin-Resistant Staphylococcus aureus* , Staphylococcal Infections*/drug therapy , Osteomyelitis*/drug therapy, Mice ; Animals ; Vancomycin/therapeutic use ; Methicillin/therapeutic use ; Anti-Bacterial Agents/pharmacology ; Methicillin Resistance ; Osseointegration ; Disease Models, Animal
مستخلص: Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve "target-and-release" drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.
(© 2023. West China School of Stomatology Sichuan University.)
التعليقات: Update of: Res Sq. 2023 May 11;:. (PMID: 37214929)
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معلومات مُعتمدة: P30 AR069655 United States AR NIAMS NIH HHS; P50 AR072000 United States AR NIAMS NIH HHS; R44 AI125060 United States AI NIAID NIH HHS
المشرفين على المادة: 6Q205EH1VU (Vancomycin)
Q91FH1328A (Methicillin)
0 (Anti-Bacterial Agents)
9TD681796G (sitafloxacin)
تواريخ الأحداث: Date Created: 20231017 Date Completed: 20231023 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10582111
DOI: 10.1038/s41413-023-00287-4
PMID: 37848449
قاعدة البيانات: MEDLINE
الوصف
تدمد:2095-4700
DOI:10.1038/s41413-023-00287-4