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

Julia Goetz; Verena Keyssner; Frank Hanses; Felix Greimel; Franziska Leiß; Timo Schwarz; Hans-Robert Springorum; Joachim Grifka; Jens Schaumburger

doi:10.1302/2046-3758.113.BJR-2021-0268.R1

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 Res. 2022 Mar;11(3):143-151. doi: 10.1302/2046-3758.113.BJR-2021-0268.R1.

Authors

Julia Goetz¹, Verena Keyssner¹, Frank Hanses², Felix Greimel¹, Franziska Leiß¹, Timo Schwarz¹, Hans-Robert Springorum¹, Joachim Grifka¹, Jens Schaumburger¹

Affiliations

¹ Department of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, Germany.
² Department of Infectology, University Hospital Regensburg, Regensburg, Germany.

PMID: 35227086
PMCID: PMC8962855
DOI: 10.1302/2046-3758.113.BJR-2021-0268.R1

Abstract

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.

Keywords: Antibiotics monotherapy; Combination antibiotics therapies; Infection of the artificial joint; Linezolid and rifampin; MRSA; Rifampin or cotrimoxazole; Vancomycin; antibiotic therapies; antibiotics; clinical studies; femur; joint infections; methicillin-resistant Staphylococcus aureus (MRSA); rat model; rifampicin; strains; vancomycin.