Grimsrud Christopher, Raven Raymond, Fothergill A W, Kim Hubert T
Department of Orthopedic Surgery, University of California, San Francisco, California 94143, USA.
Orthopedics. 2011 Aug 8;34(8):e378-81. doi: 10.3928/01477447-20110627-05.
The use of antimicrobial-loaded delivery vehicles, most often as antibiotic beads, is common practice for the treatment of deep musculoskeletal infections. The elution of antibacterial drugs from various bone cements has been extensively studied. However, much less is known about the elution of other antimicrobials from these materials. In particular, the use of this approach for fungal infections has not been well studied despite growing concern about these difficult-to-treat organisms. Voriconazole is a broad-spectrum and highly effective antifungal that has been used in the treatment of resistant fungal pathogens. We examined the in vitro elution characteristics of voriconazole from nonabsorbable polymethylmethacrylate (PMMA) beads and from absorbable calcium sulfate beads. Voricanazole-containing beads were immersed in a 5-mL bath of phosphate-buffered saline at room temperature and placed on an orbital shaker. Eluent samples were collected over the course of 2 weeks. Concentrations of the antifungal drug in solution were measured using high-performance liquid chromatography. To verify biologic activity of the eluted antifungal, collected samples were also tested against control yeasts. We found that samples collected out to 2 weeks contained relatively high voriconazole concentrations and enough active antifungal activity to inhibit growth of the control yeasts. These data demonstrate that voriconazole retains its antifungal activity when mixed into either PMMA or calcium sulfate beads, and elutes out of beads at biologically effective concentrations over a time period of at least 2 weeks. Therefore, incorporation of voriconazole into either absorbable or nonabsorbable beads appears to be a reasonable strategy for the local delivery of a potent, broad-spectrum antifungal agent to an infected wound bed.
使用负载抗菌剂的递送载体，最常见的是作为抗生素珠，是治疗深部肌肉骨骼感染的常用方法。从各种骨水泥中洗脱抗菌药物已得到广泛研究。然而，对于这些材料中其他抗菌剂的洗脱情况知之甚少。特别是，尽管对这些难以治疗的病原体的关注度不断提高，但这种方法用于真菌感染的研究还不够充分。伏立康唑是一种广谱高效的抗真菌药物，已用于治疗耐药真菌病原体。我们研究了伏立康唑从不可吸收的聚甲基丙烯酸甲酯（PMMA）珠和可吸收的硫酸钙珠中的体外洗脱特性。将含伏立康唑的珠子在室温下浸入5毫升磷酸盐缓冲盐水中，并置于轨道振荡器上。在2周内收集洗脱液样本。使用高效液相色谱法测量溶液中抗真菌药物的浓度。为了验证洗脱的抗真菌药物的生物活性，收集的样本也针对对照酵母进行了测试。我们发现，在2周内收集的样本含有相对较高的伏立康唑浓度和足够的活性抗真菌活性以抑制对照酵母的生长。这些数据表明，伏立康唑与PMMA或硫酸钙珠混合时保留其抗真菌活性，并在至少2周的时间段内以生物有效浓度从珠子中洗脱出来。因此，将伏立康唑掺入可吸收或不可吸收的珠子中似乎是将强效广谱抗真菌剂局部递送至感染伤口床的合理策略。
