Polymethylmethacrylate (PMMA) bone cement mixed with antibiotics is used in orthopedic surgery to cope with implant-related infections which are typically associated with the formation of bacterial biofilms. Taking into account the growing bacterial resistance to current antibiotics, we examined here the efficacy of a selected antimicrobial peptide (AMP) mixed into the bone cement to inhibit bacterial adhesion and the consequent biofilm formation on its surface. In particular, we followed the formation of bacterial biofilms of methicillin-resistant Staphylococcus aureus (MRSA) on implants made from PMMA bone cement loaded with AMP composed of 12 amino acid residues. This was evaluated by CFU counting of bacteria released by sonication from the biofilms formed on their surfaces after these implants were retrieved from the infected murine femoral canals. The AMP loaded in these model implants prevented adhesion of MRSA and the subsequent formation of MRSA biofilm on the surfaces of more than 80% of these implants, whereas biofilms did form on control implants made from the plain cement. The results of our experiments performed in the murine femoral canal indicate the potential for this murine osteomyelitis model to mimic actual operations in orthopedics.

• Klíčová slova
• Antimicrobial peptide, Bacterial biofilm, Implant-related infections, Murine model, PMMA implants, Polymethylmethacrylate bone cement,
• MeSH
• aminokyseliny MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• antimikrobiální peptidy MeSH
• biofilmy MeSH
• kostní cementy MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• ortopedické výkony * MeSH
• polymethylmethakrylát chemie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• antibakteriální látky MeSH
• antimikrobiální peptidy MeSH
• kostní cementy MeSH
• polymethylmethakrylát MeSH

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.

• Klíčová slova
• antimicrobial peptides, bone cement, femur heads, implant-related infections, osteomyelitis,
• Publikační typ
• časopisecké články MeSH

Joint replacement infections and osteomyelitis are among the most serious complications in orthopaedics and traumatology. The risk factors for these infections are often bacterial resistance to antimicrobials. One of the few solutions available to control bacterial resistance involves antimicrobials, which have a different mechanism of action from traditional antibiotics. Antimicrobial peptides (AMP) appear to be highly promising candidates in the treatment of resistant infections. We have identified several AMP in the venom of various wild bees and designed analogues that show potent antimicrobial activity and low toxicity against eukaryotic cells. The aim of the present study was to test the efficacy of one of those synthetic peptide analogues for the treatment of acute osteomyelitis invoked in laboratory rats. Femoral cavities of 20 laboratory Wistar rats were infected with Staphylococcus aureus. After 1 week, eight rats received an injectable calcium phosphate carrier alone, another eight rats were treated with a calcium phosphate mixed with AMP, and four rats were left without any further treatment. After another week, all rats were euthanized and radiographs were made of both the operated and healthy limbs. The animals with the carrier alone exhibited more severe acute osteomyelitis on radiographs in comparison to the recipients of the calcium phosphate carrier loaded AMP and untreated infected individuals. Based on the results of the above mentioned experiment, it was concluded that when injected directly into the site of femoral acute osteomyelitis, the calcium phosphate carrier mixed with AMP reduced osteomyelitis signs visible on radiographs.

• MeSH
• antibakteriální látky aplikace a dávkování   MeSH
• fosforečnany vápenaté farmakologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• osteomyelitida farmakoterapie   mikrobiologie   MeSH
• peptidy aplikace a dávkování   MeSH
• potkani Wistar MeSH
• stafylokokové infekce farmakoterapie   mikrobiologie   MeSH
• Staphylococcus aureus účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• calcium phosphate MeSH Prohlížeč
• fosforečnany vápenaté MeSH
• peptidy MeSH