Search

A major antimicrobial resistance mechanism in Gram-negative bacteria is the production of β-lactamase enzymes. The increasing emergence of β-lactamase-producing multi-drug-resistant "superbugs" has resulted in increases in costly hospital Emergency Department (ED) visits and hospitalizations due to the requirement for parenteral antibiotic therapy for infections caused by these difficult-to-treat bacteria. To address the lack of outpatient treatment, we initiated an iterative program combining medicinal chemistry, biochemical testing, microbiological profiling, and evaluation of oral pharmacokinetics. Lead optimization focusing on multiple smaller, more lipophilic active compounds, followed by an exploration of oral bioavailability of a variety of their respective prodrugs, provided 36 (VNRX-7145/VNRX-5236 etzadroxil), the prodrug of the boronic acid-containing β-lactamase inhibitor 5 (VNRX-5236). In vitro and in vivo studies demonstrated that 5 restored the activity of the oral cephalosporin antibiotic ceftibuten against Enterobacterales expressing Ambler class A extended-spectrum β-lactamases, class A carbapenemases, class C cephalosporinases, and class D oxacillinases.

Here we report a study of artisanal grain, coffee, ice cream, cheese, and chocolate made in the Philadelphia and New York areas, exploring the chemistry responsible for the differences between artisanal and mass-produced food, the rationale that artisans have toward making their products, and consumer attitudes toward purchasing artisanal food. The contrasting techniques used in manufacturing these two classes of food lead to differences in composition, flavor, and texture. Dairy products made from pasture-fed cows, for instance, display more complex flavor profiles owing to the greater variety of plants the animals consume. Consumers are willing to pay more for artisanal food, feeling that it tastes better, is healthier, and helps support family-owned operations. Producers not only want to be able to control their businesses, but also wish to create better and more-authentic food in an environmentally friendly manner. The psychology surrounding artisanal food is partly based on their chemistry., Competing Interests: Competing interestsThe authors declare no competing interests.