The in vivo antibacterial effect of ATX-FSL on methicillin-resistant staphylococcus epidermidis infected implants in rats
According to the World Health Organization (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 addition to antibacterial effect, in vitro experiments show that APIM-peptides lead 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 and Staphylococcus Epidermidis.
Infection is a devastating event for a patient in prosthetic 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 orthopedic 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 further test the potential of APIM-peptides as an antibiotic drug an in vivo experiment is necessary since the event of an infection is an in vivo event difficult to mimic in vitro. This experiment will be a continuation of a pilot experiment including 28 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 parallels. To refine the experiment it will be performed in three different stages to optimize the time frame of the experiment and method of inserting inoculum of bacterial suspension into the bone grafts. This is important as we observed differences in bacterial growth (also within the control group) in the pilot experiment. 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 addition to antibacterial effect, in vitro experiments show that APIM-peptides lead 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 and Staphylococcus Epidermidis.
Infection is a devastating event for a patient in prosthetic 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 orthopedic 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 further test the potential of APIM-peptides as an antibiotic drug an in vivo experiment is necessary since the event of an infection is an in vivo event difficult to mimic in vitro. This experiment will be a continuation of a pilot experiment including 28 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 parallels. To refine the experiment it will be performed in three different stages to optimize the time frame of the experiment and method of inserting inoculum of bacterial suspension into the bone grafts. This is important as we observed differences in bacterial growth (also within the control group) in the pilot experiment. The expected distress of the animals is moderate pain after surgery and anesthesia.