It has been predicted that AMR could cause as many as 10 million deaths/year by 2050 with a global economic burden of USD 100 trillion 3, 4.Īlthough the need for new antibiotics is urgent, it seems that no single response is sufficient to fight AMR 5, 6. It is estimated that approximately 700,000 deaths/year globally are due to drug-resistant bacteria 1, 2. Rising antimicrobial resistance (AMR) is one of the greatest health challenges the world currently faces. Finally, repeated administration of SET-M33 by short infusion in dogs revealed a no-observed-adverse-effect-level of 0.5 mg/kg/day. Neurological toxicity measurements by the Irwin method and respiratory function evaluation in rats did not reveal any toxic effect even at the highest dose. This was also confirmed by necroscopy studies of animal tissues, where signs of degeneration and regeneration were found in kidney when SET-M33 was administered at the highest doses in the two animal species. Clinical laboratory investigations in dogs and rats showed a dose-related increase in creatinine and urea levels, indicating that the kidneys are the target organ. Dose range finding experiments determined the doses to use in toxicokinetic evaluation, clinical biochemistry analysis, necroscopy and in neurological and respiratory measurements. Here we report the toxicological evaluation of SET-M33 administered intravenously to rats and dogs. The antimicrobial peptide SET-M33 is under study for the development of a new antibiotic against major Gram-negative pathogens.
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