A potent antibiotic-loaded bone-cement implant against staphylococcal bone infections.

Autor: Ghosh S; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Sinha M; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Samanta R; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Sadhasivam S; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Bhattacharyya A; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Nandy A; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Saini S; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Tandon N; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Singh H; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Gupta S; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Chauhan A; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Aavula KK; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Varghese SS; Department of Biotechnology, Indian Institute of Technology, Kharagpur, India., Shi P; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Ghosh S; Department of Biotechnology, Indian Institute of Technology, Kharagpur, India., Garg MK; Vyome Therapeutics Inc., Princeton, NJ, USA.; Vyome Therapeutics Limited, New Delhi, India., Saha T; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA., Padhye A; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Ghosh S; Vyome Therapeutics Inc., Princeton, NJ, USA. shamik.ghosh@vyometx.com.; Vyome Therapeutics Limited, New Delhi, India. shamik.ghosh@vyometx.com., Jang HL; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. hjang@bwh.harvard.edu.; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. hjang@bwh.harvard.edu.; Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. hjang@bwh.harvard.edu., Sengupta S; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ssengupta2@bwh.harvard.edu.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. ssengupta2@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2022 Oct; Vol. 6 (10), pp. 1180-1195. Date of Electronic Publication: 2022 Oct 13.
DOI: 10.1038/s41551-022-00950-x
Abstrakt: New antibiotics should ideally exhibit activity against drug-resistant bacteria, delay the development of bacterial resistance to them and be suitable for local delivery at desired sites of infection. Here, we report the rational design, via molecular-docking simulations, of a library of 17 candidate antibiotics against bone infection by wild-type and mutated bacterial targets. We screened this library for activity against multidrug-resistant clinical isolates and identified an antibiotic that exhibits potent activity against resistant strains and the formation of biofilms, decreases the chances of bacterial resistance and is compatible with local delivery via a bone-cement matrix. The antibiotic-loaded bone cement exhibited greater efficacy than currently used antibiotic-loaded bone cements against staphylococcal bone infections in rats. Potent and locally delivered antibiotic-eluting polymers may help address antimicrobial resistance.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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