Faber Christopher, Hoogendoorn Roel J W, Stallmann Hein P, Lyaruu D M, van Nieuw Amerongen Arie, Wuisman Paul I J M
Department of Orthopaedic Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
J Antimicrob Chemother. 2004 Dec;54(6):1078-84. doi: 10.1093/jac/dkh441. Epub 2004 Nov 10.
The continued rise in drug-resistant pathogens has led to global research efforts into new antimicrobial agents. A promising class of new agents are the antimicrobial peptides. The aim of the study was to investigate the efficacy of the antimicrobial peptide Dhvar-5 in a prophylactic, methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model.
Dhvar-5 (12 mg or 24 mg/rabbit) was incorporated into polymethyl methacrylate (PMMA) beads as a local drug delivery system. For comparison, plain beads (control) and beads containing gentamicin as a sulphate (10 mg or 24 mg per rabbit) were also prepared. The beads were inserted into the inoculated femoral cavity of 36 rabbits, and 1 week later they were killed. The presence and severity of MRSA osteomyelitis was assessed by culture and histology.
Both the 24 mg Dhvar-5 beads and the 24 mg gentamicin sulphate beads significantly reduced the bacterial load of the inoculated femora compared with the control chain. Although a 24 mg Dhvar-5 dose inhibited MRSA growth, it did not completely sterilize the femora. Sterilization occurred only in some of the gentamicin-treated specimens.
We conclude that both the gentamicin beads and the Dhvar-5 beads were only partially effective at preventing MRSA infection in this model.
耐药病原体的持续增加促使全球致力于新型抗菌药物的研究。一类有前景的新型药物是抗菌肽。本研究的目的是在耐甲氧西林金黄色葡萄球菌（MRSA）骨髓炎预防性模型中研究抗菌肽Dhvar-5的疗效。
将Dhvar-5（12毫克或24毫克/只兔子）掺入聚甲基丙烯酸甲酯（PMMA）珠中作为局部给药系统。为作比较，还制备了空白珠（对照）和含硫酸庆大霉素的珠（每只兔子10毫克或24毫克）。将这些珠子植入36只兔子接种后的股骨髓腔，1周后将兔子处死。通过培养和组织学评估MRSA骨髓炎的存在和严重程度。
与对照相比，24毫克Dhvar-5珠和24毫克硫酸庆大霉素珠均显著降低了接种股骨的细菌载量。虽然24毫克Dhvar-5剂量抑制了MRSA生长，但未完全清除股骨中的细菌。仅在一些庆大霉素处理的标本中实现了杀菌。
我们得出结论，在该模型中，庆大霉素珠和Dhvar-5珠在预防MRSA感染方面均仅部分有效。
