Goetz Julia, Keyssner Verena, Hanses Frank, Greimel Felix, Leiß Franziska, Schwarz Timo, Springorum Hans-Robert, Grifka Joachim, Schaumburger Jens
Department of Orthopaedic Surgery, University Hospital Regensburg - Asklepios Bad Abbach, Regensburg, Germany.
Department of Infectology, University Hospital Regensburg, Regensburg, Germany.
Bone Joint Res. 2022 Mar;11(3):143-151. doi: 10.1302/2046-3758.113.BJR-2021-0268.R1.
Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant (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.
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.
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.
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: 2022;11(3):143-151.
人工关节周围感染（PJI）较为罕见，但给患者带来了巨大负担。此外，耐甲氧西林金黄色葡萄球菌（MRSA）的发病率正在上升。因此，本大鼠实验的目的是比较治疗由MRSA引起的PJI常用的抗生素。
为此，将灭菌的钢植入物植入77只大鼠的股骨。金属装置接种两种不同MRSA菌株的悬液。将动物分成几组，分别用万古霉素、利奈唑胺、复方新诺明或利福平进行单药治疗，或联合使用抗生素，持续14天。在无抗生素间隔两天后，取出植入物，并对骨、肌肉和关节周围组织进行微生物学分析。
万古霉素和利奈唑胺能够显著（p<0.05）降低植入物上的MRSA细菌数量。在骨组织上未发现显著效果。利福平是唯一能显著降低植入物和骨组织上细菌数量的单药治疗。与万古霉素或利奈唑胺联合使用显示出显著疗效。单独使用复方新诺明治疗未能显著降低细菌数量。在两项试验中，利奈唑胺加 rifampin联合治疗在植入物和骨组织上均比对照组显著更有效。
尽管利福平作为单药治疗有效，但由于耐药性发生率高，不应使用。我们的动物实验表明联合抗生素治疗非常重要。未来，有必要进行更高病例数、不同细菌浓度和个体药物剂量变化的研究，以便能够进行精确比较，可能需要在临床试验中进行。引用本文：2022；11（3）：143-151。
