Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA

Aims Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment o...

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Main Authors: Julia Goetz, Verena Keyssner, Frank Hanses, Felix Greimel, Franziska Leiß, Timo Schwarz, Hans-Robert Springorum, Joachim Grifka, Jens Schaumburger
Format: Article
Language:English
Published: The British Editorial Society of Bone & Joint Surgery 2022-03-01
Series:Bone & Joint Research
Subjects:
Online Access:https://online.boneandjoint.org.uk/doi/10.1302/2046-3758.113.BJR-2021-0268.R1
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author Julia Goetz
Verena Keyssner
Frank Hanses
Felix Greimel
Franziska Leiß
Timo Schwarz
Hans-Robert Springorum
Joachim Grifka
Jens Schaumburger
author_facet Julia Goetz
Verena Keyssner
Frank Hanses
Felix Greimel
Franziska Leiß
Timo Schwarz
Hans-Robert Springorum
Joachim Grifka
Jens Schaumburger
author_sort Julia Goetz
collection DOAJ
description Aims Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151.
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spelling doaj.art-5d72610a7f3a436ab079958466d2326b2022-12-21T21:11:07ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582022-03-0111314315110.1302/2046-3758.113.BJR-2021-0268.R1Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSAJulia Goetz0Verena Keyssner1Frank Hanses2Felix Greimel3Franziska Leiß4Timo Schwarz5Hans-Robert Springorum6Joachim Grifka7Jens Schaumburger8Department of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyDepartment of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyDepartment of Infectology, University Hospital Regensburg, Regensburg, GermanyDepartment of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyDepartment of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyDepartment of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyDepartment of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyDepartment of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyDepartment of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, GermanyAims Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151.https://online.boneandjoint.org.uk/doi/10.1302/2046-3758.113.BJR-2021-0268.R1MRSAInfection of the artificial jointCombination antibiotics therapiesAntibiotics monotherapyVancomycinRifampin or cotrimoxazole
spellingShingle Julia Goetz
Verena Keyssner
Frank Hanses
Felix Greimel
Franziska Leiß
Timo Schwarz
Hans-Robert Springorum
Joachim Grifka
Jens Schaumburger
Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA
Bone & Joint Research
MRSA
Infection of the artificial joint
Combination antibiotics therapies
Antibiotics monotherapy
Vancomycin
Rifampin or cotrimoxazole
title Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA
title_full Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA
title_fullStr Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA
title_full_unstemmed Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA
title_short Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA
title_sort animal experimental investigation on the efficacy of antibiotic therapy with linezolid vancomycin cotrimoxazole and rifampin in treatment of periprosthetic knee joint infections by mrsa
topic MRSA
Infection of the artificial joint
Combination antibiotics therapies
Antibiotics monotherapy
Vancomycin
Rifampin or cotrimoxazole
url https://online.boneandjoint.org.uk/doi/10.1302/2046-3758.113.BJR-2021-0268.R1
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