Glycopeptide antibiotic combination therapy

Abstract

Bacterial infections evading the current antibiotic arsenal warrant new treatment options. The mainstay treatment forinfections involves administration of the broad-spectrum antibiotic vancomycin, which also depletes the gut microbiome and its natural defenses. This leads to recurrentinfections in 20-30% of patients. Alternative treatment options are limited, triggering a perpetual cycle of relapse and recovery that may eventually lead to death. Keratinicyclin B represents a glycopeptide antibiotic chemotype with a mechanism of action that is selective for Clostridia. When combined, vancomycin (or other glycopeptide antibiotic) and keratinicyclin B interact synergistically to inhibit the growth ofat concentrations far lower than their respective minimal inhibitory concentrations. Such a combination therapy could allow for targeted colonization clearance at low antibiotic doses, thereby minimizing toxicity and reducing the likelihood of relapse.