Laboratory for Musculoskeletal Research and Innovation, Department of Orthopaedics, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2012;7(12):e52883. doi: 10.1371/journal.pone.0052883. Epub 2012 Dec 20.
Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone). Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.
利福平目前被认为是对抗革兰氏阳性植入物相关感染最有效的药物。利福平的使用受到细菌耐药性的限制,通常通过联合使用第二种抗生素来管理。本研究的目的是确定将可溶性利福平与固定在钛金属上的万古霉素联合使用作为控制体外细菌生长和耐药性的手段的有效性。当万古霉素固定在钛盘上处理金黄色葡萄球菌接种物≤2×10⁶ CFU 时,细菌生长受到抑制,但接种物大于 2×10⁶ CFU/盘会附着并存活。表面固定的万古霉素与可溶性利福平联合使用,增强了利福平对 10⁶ CFU/cm²接种物的抑制作用,使利福平的组合 MIC 值降低了一个稀释度(组合 MIC 值为 0.008 mg/L,而单独使用利福平时为 0.015 mg/L)。此外,表面固定的万古霉素防止了在 2×10⁸ CFU 接种物中出现利福平耐药菌。