Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activity
Abstract Implant-associated osteomyelitis (IAOM) is a severe complication of the usage of orthopaedic implants. IAOM is difficult to treat and infection relapse is often due to insufficient treatment of bacterial persister cells. The anthelmintic drug bithionol is promising in combating persister ce...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-08879-2 |
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| author | Anders Marthinsen Seefeldt Mikkel Illemann Johansen Freja Winther Sillesen Maiken Engelbrecht Petersen Lars Østergaard Rikke Louise Meyer Nis Pedersen Jørgensen |
| author_facet | Anders Marthinsen Seefeldt Mikkel Illemann Johansen Freja Winther Sillesen Maiken Engelbrecht Petersen Lars Østergaard Rikke Louise Meyer Nis Pedersen Jørgensen |
| author_sort | Anders Marthinsen Seefeldt |
| collection | DOAJ |
| description | Abstract Implant-associated osteomyelitis (IAOM) is a severe complication of the usage of orthopaedic implants. IAOM is difficult to treat and infection relapse is often due to insufficient treatment of bacterial persister cells. The anthelmintic drug bithionol is promising in combating persister cells - including Staphylococcus aureus persister cells. We investigated bithionol alone and in combination with antibiotics both in vitro and in vivo, using a murine IAOM model. In vitro experiments confirmed bithionol’s anti-persister activity against S. aureus, demonstrating significant CFU reductions in combination with daptomycin and moxifloxacin. In the murine IAOM model, moxifloxacin led to a small but significant reduction in bacterial load in bone of approx. log 0.5 CFU/ml. However, combining bithionol with antibiotics did not further reduce bacterial load in either bone or on implants. We subsequently demonstrated dramatically reduced activity of bithionol in the presence of albumin, suggesting low bioavailability in vivo. Despite promising in vitro results, bithionol’s efficacy against persister cells did not translate into improving treatment outcome the IAOM model. The study highlights the challenges in translating in vitro findings to in vivo outcomes, and future research into application of bithionol to treat bacterial infections must first address its bioavailability or investigate local delivery options. |
| format | Article |
| id | doaj-art-d52ff2188eab4646a4a72efcc40fdc63 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-d52ff2188eab4646a4a72efcc40fdc632025-08-20T03:45:52ZengNature PortfolioScientific Reports2045-23222025-07-011511810.1038/s41598-025-08879-2Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activityAnders Marthinsen Seefeldt0Mikkel Illemann Johansen1Freja Winther Sillesen2Maiken Engelbrecht Petersen3Lars Østergaard4Rikke Louise Meyer5Nis Pedersen Jørgensen6Department of Infectious Diseases, Aarhus University HospitalDepartment of Infectious Diseases, Aarhus University HospitalInterdisciplinary Nanoscience Center (iNANO), Aarhus UniversityInterdisciplinary Nanoscience Center (iNANO), Aarhus UniversityDepartment of Infectious Diseases, Aarhus University HospitalInterdisciplinary Nanoscience Center (iNANO), Aarhus UniversityDepartment of Infectious Diseases, Aarhus University HospitalAbstract Implant-associated osteomyelitis (IAOM) is a severe complication of the usage of orthopaedic implants. IAOM is difficult to treat and infection relapse is often due to insufficient treatment of bacterial persister cells. The anthelmintic drug bithionol is promising in combating persister cells - including Staphylococcus aureus persister cells. We investigated bithionol alone and in combination with antibiotics both in vitro and in vivo, using a murine IAOM model. In vitro experiments confirmed bithionol’s anti-persister activity against S. aureus, demonstrating significant CFU reductions in combination with daptomycin and moxifloxacin. In the murine IAOM model, moxifloxacin led to a small but significant reduction in bacterial load in bone of approx. log 0.5 CFU/ml. However, combining bithionol with antibiotics did not further reduce bacterial load in either bone or on implants. We subsequently demonstrated dramatically reduced activity of bithionol in the presence of albumin, suggesting low bioavailability in vivo. Despite promising in vitro results, bithionol’s efficacy against persister cells did not translate into improving treatment outcome the IAOM model. The study highlights the challenges in translating in vitro findings to in vivo outcomes, and future research into application of bithionol to treat bacterial infections must first address its bioavailability or investigate local delivery options.https://doi.org/10.1038/s41598-025-08879-2 |
| spellingShingle | Anders Marthinsen Seefeldt Mikkel Illemann Johansen Freja Winther Sillesen Maiken Engelbrecht Petersen Lars Østergaard Rikke Louise Meyer Nis Pedersen Jørgensen Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activity Scientific Reports |
| title | Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activity |
| title_full | Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activity |
| title_fullStr | Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activity |
| title_full_unstemmed | Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activity |
| title_short | Bithionol is ineffective in a mouse model of S. aureus implant-associated osteomyelitis despite potent in vitro activity |
| title_sort | bithionol is ineffective in a mouse model of s aureus implant associated osteomyelitis despite potent in vitro activity |
| url | https://doi.org/10.1038/s41598-025-08879-2 |
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