Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model
Abstract Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-04752-y |
| _version_ | 1797840854147137536 |
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| author | Neil Zhao Dylan Curry Rachel E. Evans Selin Isguven Theresa Freeman John R. Eisenbrey Flemming Forsberg Jessica M. Gilbertie Sophie Boorman Rachel Hilliard Sana S. Dastgheyb Priscilla Machado Maria Stanczak Marc Harwood Antonia F. Chen Javad Parvizi Irving M. Shapiro Noreen J. Hickok Thomas P. Schaer |
| author_facet | Neil Zhao Dylan Curry Rachel E. Evans Selin Isguven Theresa Freeman John R. Eisenbrey Flemming Forsberg Jessica M. Gilbertie Sophie Boorman Rachel Hilliard Sana S. Dastgheyb Priscilla Machado Maria Stanczak Marc Harwood Antonia F. Chen Javad Parvizi Irving M. Shapiro Noreen J. Hickok Thomas P. Schaer |
| author_sort | Neil Zhao |
| collection | DOAJ |
| description | Abstract Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does not increase antibiotic activity. Importantly, in the porcine model of septic arthritis, no bacteria are recovered from the SynF after treatment with amikacin and UTMD—ultrasound without UTMD is insufficient. Our data suggest that UTMD + antibiotics may serve as an important adjunct for the treatment of septic arthritis. |
| first_indexed | 2024-04-09T16:21:31Z |
| format | Article |
| id | doaj.art-627472f195d14f95b1ffedf742626fba |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-09T16:21:31Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-627472f195d14f95b1ffedf742626fba2023-04-23T11:25:34ZengNature PortfolioCommunications Biology2399-36422023-04-016111110.1038/s42003-023-04752-yMicrobubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis modelNeil Zhao0Dylan Curry1Rachel E. Evans2Selin Isguven3Theresa Freeman4John R. Eisenbrey5Flemming Forsberg6Jessica M. Gilbertie7Sophie Boorman8Rachel Hilliard9Sana S. Dastgheyb10Priscilla Machado11Maria Stanczak12Marc Harwood13Antonia F. Chen14Javad Parvizi15Irving M. Shapiro16Noreen J. Hickok17Thomas P. Schaer18Department of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Radiology, Thomas Jefferson UniversityDepartment of Radiology, Thomas Jefferson UniversityDepartment of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of PennsylvaniaDepartment of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of PennsylvaniaDepartment of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of PennsylvaniaDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Radiology, Thomas Jefferson UniversityDepartment of Radiology, Thomas Jefferson UniversityRothman Orthopaedic InstituteDepartment of Orthopaedic Surgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Orthopaedic Surgery, Sidney Kimmel College, Thomas Jefferson UniversityDepartment of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of PennsylvaniaAbstract Treatment failure in joint infections is associated with fibrinous, antibiotic-resistant, floating and tissue-associated Staphylococcus aureus aggregates formed in synovial fluid (SynF). We explore whether antibiotic activity could be increased against Staphylococcus aureus aggregates using ultrasound-triggered microbubble destruction (UTMD), in vitro and in a porcine model of septic arthritis. In vitro, when bacterially laden SynF is diluted, akin to the dilution achieved clinically with lavage and local injection of antibiotics, amikacin and ultrasound application result in increased bacterial metabolism, aggregate permeabilization, and a 4-5 log decrease in colony forming units, independent of microbubble destruction. Without SynF dilution, amikacin + UTMD does not increase antibiotic activity. Importantly, in the porcine model of septic arthritis, no bacteria are recovered from the SynF after treatment with amikacin and UTMD—ultrasound without UTMD is insufficient. Our data suggest that UTMD + antibiotics may serve as an important adjunct for the treatment of septic arthritis.https://doi.org/10.1038/s42003-023-04752-y |
| spellingShingle | Neil Zhao Dylan Curry Rachel E. Evans Selin Isguven Theresa Freeman John R. Eisenbrey Flemming Forsberg Jessica M. Gilbertie Sophie Boorman Rachel Hilliard Sana S. Dastgheyb Priscilla Machado Maria Stanczak Marc Harwood Antonia F. Chen Javad Parvizi Irving M. Shapiro Noreen J. Hickok Thomas P. Schaer Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model Communications Biology |
| title | Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model |
| title_full | Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model |
| title_fullStr | Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model |
| title_full_unstemmed | Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model |
| title_short | Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model |
| title_sort | microbubble cavitation restores staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model |
| url | https://doi.org/10.1038/s42003-023-04752-y |
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