The recognition of LpxC inhibitors as potential antibiotics could revolutionise the management of sepsis in veterinary patients if their unknown biological properties are widely evaluated in suitable animal models

Current studies continue to show that UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetyl glucosamine deacetylase (LpxC) inhibitors such as pyridone methylsulfone hydroxymate 1 and 2a (LpxC-2) downregulate the lethal effects of sepsis initiated by multi-drug resistant Gram-negative bacteria (MDRGNB) by curtailing lipopolysaccharide (LPS) synthesis in murine models. Sepsis initiated by MDRGNB is a leading cause of shock and systemic inflammatory response syndrome (SIRS) in intensive care unit (ICU) patients. To date however, the biological effects of LpxC-2 and related molecules in companion and production animals remain largely unexplored in vivo and are therefore unknown. Such studies would be greatly informative in the expectation of LpxC-2 progressing to human clinical trials. Mechanistic studies to interrogate this novel antibiotic candidate in realistic and clinically applicable large animal models of veterinary importance are sorely lacking. To be relevant, the physiology of the chosen animal models should closely match that of humans such as ovine or porcine, or even better, non-human primate based studies, as they are more genetically similar to humans than murine models. If discovered to have subtle or negligible side effects, LpxC-2 could have a future role in the treatment and management of MDRGNB-induced infections that lead to sepsis in both animals and humans. More research is indicated on LpxC-2 use in many veterinary species, as data remains scarce.