Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Rochester, Minnesota, USA.
Division of Biomedical Statistics and Informatics.
J Infect Dis. 2020 Oct 1;222(9):1498-1504. doi: 10.1093/infdis/jiaa401.
Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis.
Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively.
Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group.
Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.
由于患者不耐受或药物相互作用,需要替代利福平的药物来治疗葡萄球菌假体周围关节感染。在本研究中,我们评估了利福布汀、利福喷丁和利福平,以及是否联合万古霉素,在大鼠异物性骨髓炎模型中的疗效。
将耐甲氧西林金黄色葡萄球菌(MRSA)接种到胫骨近端,并在每根胫骨中植入一根克氏针。感染 4 周后,单独或联合万古霉素给予利福平、利福布汀或利福喷丁。培养胫骨和克氏针,并报告每克骨或每根克氏针的 log10 菌落形成单位(CFU)的中位数。
与未治疗组(4.36 log10 CFU/g)或万古霉素单药组(4.64 log10 CFU/g)相比,联合万古霉素给予利福平、利福布汀或利福喷丁治疗组从骨中分离出的 MRSA 更少(分别为 0.10、3.02 和 0.10 log10 CFU/g)(均 P ≤ 0.02)。未治疗或万古霉素单药治疗组的克氏针分别回收了中位数为 1.76 和 2.91 log10 CFU/g/根的 MRSA。相比之下,联合万古霉素给予利福平、利福布汀和利福喷丁治疗组,克氏针的 MRSA 中位数分别为 0.1 log10 CFU/g。在利福平单药治疗组中,检测到 1 只动物对利福平耐药。
利福布汀或利福喷丁联合万古霉素与利福平联合万古霉素对大鼠异物性骨髓炎中的 MRSA 同样有效,这表明利福布汀和/或利福喷丁可能是葡萄球菌假体周围关节感染临床治疗中利福平的替代药物。