The in vivo antibacterial effect of ATX-FSL on methicillin-resistant staphylococcus epidermidis infected implants in rats
According to the World Health Organisation (WHO) report on antimicrobial resistance (2014) the antimicrobial resistance is an increasing serious global threat to public health where new resistance mechanisms emerge and spread globally. New antibiotics are therefore in demand.
In vitro experiments show antibacterial effect of APIM-peptides on several Multiple Drug Resistant (MDR) bacterial strains, and thus potential as a new antibiotic drug. In addtion to antibacterial effect, in vitro experiments show that APIM-peptides leads to decrease in mutation frequency in several bacterial strains. Mutagenesis is one of the mechanisms important for the bacterial development of resistance and APIM-peptides could therefore be a potential drug to combine with other antibiotics to avoid mutagenesis and development of resistance. In vitro experiments have also shown that the combination of gentamicin and APIM-peptides inhibits the development of resistance against gentamicin in E. coli.
Infection is a devestating event for a patient in prostethic surgery. This is further complicated by the emergence of new MDR bacteria and less effective antibiotics. In this experiment the antibacterial effect of an APIM-peptide, ATX-FSL, will be measured in a rat model that mimics a chronic orthopaedic implant infection of methicillin-resistant staphylococcus epidermidis (MRSE). The implant, a bone graft, will be infected with the bacterial strain and treated with ATX-FSL alone and in combination with gentamicin.
To furthr test the potential of APIM-peptides as an antibotic drug an in vivo experiment is neccessary since the event of an infection is an in vivo event difficult to mimic in vitro. This experiment will be a pilot inculding 20 albino outbred Wistar rats. To limit the number of animals used in this experiment there will be included two bone grafts in each animal giving more technical paralells. To refine the experiment it will be performed in three different stages to allow for adjustments of the duration of the experiment and the doses of APIM-peptides and gentamicin. the expected distress of the animals is moderate pain after surgery and anesthesia.
In vitro experiments show antibacterial effect of APIM-peptides on several Multiple Drug Resistant (MDR) bacterial strains, and thus potential as a new antibiotic drug. In addtion to antibacterial effect, in vitro experiments show that APIM-peptides leads to decrease in mutation frequency in several bacterial strains. Mutagenesis is one of the mechanisms important for the bacterial development of resistance and APIM-peptides could therefore be a potential drug to combine with other antibiotics to avoid mutagenesis and development of resistance. In vitro experiments have also shown that the combination of gentamicin and APIM-peptides inhibits the development of resistance against gentamicin in E. coli.
Infection is a devestating event for a patient in prostethic surgery. This is further complicated by the emergence of new MDR bacteria and less effective antibiotics. In this experiment the antibacterial effect of an APIM-peptide, ATX-FSL, will be measured in a rat model that mimics a chronic orthopaedic implant infection of methicillin-resistant staphylococcus epidermidis (MRSE). The implant, a bone graft, will be infected with the bacterial strain and treated with ATX-FSL alone and in combination with gentamicin.
To furthr test the potential of APIM-peptides as an antibotic drug an in vivo experiment is neccessary since the event of an infection is an in vivo event difficult to mimic in vitro. This experiment will be a pilot inculding 20 albino outbred Wistar rats. To limit the number of animals used in this experiment there will be included two bone grafts in each animal giving more technical paralells. To refine the experiment it will be performed in three different stages to allow for adjustments of the duration of the experiment and the doses of APIM-peptides and gentamicin. the expected distress of the animals is moderate pain after surgery and anesthesia.