Testing the efficacy of antimicrobial peptides in the topical treatment of induced osteomyelitis in rats

Abstract

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.

Antimicrobial Peptides for Topical Treatment of Osteomyelitis and Implant-Related Infections: Study in the Spongy Bone

“…Another issue might be the toxicity of these peptides when applied locally to the bone tissue of laboratory animals or humans. As we have already published [ 35 ], we did not notice any signs of local or systemic toxicity in laboratory rats when their infected femurs were treated with peptide I. These animals did not have higher degree of swollen limbs or tissue necrosis in comparison to the untreated groups of animals.…”

Therapeutics and delivery vehicles for local treatment of osteomyelitis

“…Antimicrobial peptides (AMPs), found naturally within human neutrophils and in epithelial secretions, have gained popularity in recent years as therapeutics for osteomyelitis. 53 The list of AMPs is extensive, 54 but some investigated for S. aureus clearance include: β-defensins, 55,56 Magainin 2 (also known by its analog, pexiganan acetate), 57,58 human lactoferrin 1-11 (hLF1-11), 59,60 isolates of bee venom, [61][62][63][64] snake venom, 65 and L-homocarnosine. 66 In one interesting study, a murine model for the study of human levels.…”

Local Antibiotic Delivery Ceramic Bone Substitutes for the Treatment of Infected Bone Cavities and Bone Regeneration: A Systematic Review on What We Have Learned from Animal Models

“…Five hundred sixteen references were retrieved after a PubMed literature search. After applying the exclusion criteria, a total of 32 articles were included in this review [ 19 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. Two additional papers [ 58 , 59 ] were added to the final literature review after backward citation tracking, making a total of 34 papers.…”