Melicherčík Pavel, Nešuta Ondřej, Čeřovský Václav
Department of Orthopaedics, First Faculty of Medicine, Charles University in Prague and University Hospital in Motol, V Úvalu 84, 150 06 Prague 5, Czech Republic.
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
Pharmaceuticals (Basel). 2018 Feb 16;11(1):20. doi: 10.3390/ph11010020.
We examined the benefits of short linear α-helical antimicrobial peptides (AMPs) invented in our laboratory for treating bone infection and preventing microbial biofilm formation on model implants due to causative microorganisms of osteomyelitis. For this purpose, we introduced a model of induced osteomyelitis that utilizes human femur heads obtained from the hospital after their replacement with artificial prostheses. We found that the focus of the infection set up in the spongy part of this bone treated with AMP-loaded calcium phosphate cement was eradicated much more effectively than was the focus treated with antibiotics such as vancomycin or gentamicin loaded into the same cement. This contradicts the minimum inhibitory concentrations (MIC) values of AMPs and antibiotics against some bacterial strains obtained in standard in vitro assays. The formation of microbial biofilm on implants made from poly(methylmethacrylate)-based bone cement loaded with AMP was evaluated after the implants' removal from the infected bone sample. AMPs loaded in such model implants prevented microbial adhesion and subsequent formation of bacterial biofilm on their surface. Biofilms did form, on the other hand, on control implants made from the plain cement when these were implanted into the same infected bone sample. These results of the experiments performed in human bone tissue highlight the clinical potential of antimicrobial peptides for use in treating and preventing osteomyelitis caused by resistant pathogens.
我们研究了我们实验室发明的短线性α-螺旋抗菌肽（AMPs）在治疗骨感染以及预防因骨髓炎致病微生物导致的模型植入物上微生物生物膜形成方面的益处。为此，我们引入了一种诱导性骨髓炎模型，该模型利用从医院获取的在人工假体置换后取出的人类股骨头。我们发现，用负载AMPs的磷酸钙骨水泥处理的该骨头海绵状部分所建立的感染病灶，比用负载万古霉素或庆大霉素等抗生素的相同骨水泥处理的病灶清除得更有效。这与AMPs和抗生素在标准体外试验中针对某些细菌菌株的最低抑菌浓度（MIC）值相矛盾。在将由负载AMPs的聚甲基丙烯酸甲酯基骨水泥制成的植入物从感染骨样本中取出后，评估了其表面微生物生物膜的形成情况。负载在这种模型植入物中的AMPs可防止微生物粘附并随后在其表面形成细菌生物膜。另一方面，当将由普通骨水泥制成的对照植入物植入相同的感染骨样本中时，生物膜确实会形成。在人类骨组织中进行的这些实验结果突出了抗菌肽在治疗和预防由耐药病原体引起的骨髓炎方面的临床潜力。
