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Abstract Antimicrobial resistance (AMR) in food animals is a growing threat to animal health and potentially to human health. In resource-limited settings, allocating resources to address AMR can be guided with maps. Here, we mapped AMR prevalence in 7 antimicrobials in Escherichia coli and nontyphoidal Salmonella species across low- and middle-income countries (LIMCs), using 1088 point-prevalence surveys in combination with a geospatial model. Hotspots of AMR were predicted in China, India, Brazil, Chile, and part of central Asia and southeastern Africa. The highest resistance prevalence was for tetracycline (59% for E. coli and 54% for nontyphoidal Salmonella, average across LMICs) and lowest for cefotaxime (33% and 19%). We also identified the antimicrobial with the highest probability of resistance exceeding critical levels (50%) in the future (1.7–12.4 years) for each 10 × 10 km pixel on the map. In Africa and South America, 78% locations were associated with penicillins or tetracyclines crossing 50% resistance in the future. In contrast, in Asia, 77% locations were associated with penicillins or sulphonamides. Our maps highlight diverging geographic trends of AMR prevalence across antimicrobial classes, and can be used to target AMR surveillance in AMR hotspots for priority antimicrobial classes.

Abstract Monoacylglycerol lipase (MAGL) regulates endocannabinoid 2-arachidonoylglycerol (2-AG) and eicosanoid signalling. MAGL inhibition provides therapeutic opportunities but clinical potential is limited by central nervous system (CNS)-mediated side effects. Here, we report the discovery of LEI-515, a peripherally restricted, reversible MAGL inhibitor, using high throughput screening and a medicinal chemistry programme. LEI-515 increased 2-AG levels in peripheral organs, but not mouse brain. LEI-515 attenuated liver necrosis, oxidative stress and inflammation in a CCl4-induced acute liver injury model. LEI-515 suppressed chemotherapy-induced neuropathic nociception in mice without inducing cardinal signs of CB1 activation. Antinociceptive efficacy of LEI-515 was blocked by CB2, but not CB1, antagonists. The CB1 antagonist rimonabant precipitated signs of physical dependence in mice treated chronically with a global MAGL inhibitor (JZL184), and an orthosteric cannabinoid agonist (WIN55,212-2), but not with LEI-515. Our data support targeting peripheral MAGL as a promising therapeutic strategy for developing safe and effective anti-inflammatory and analgesic agents.

Trends in antimicrobial resistance (AMR) in aquatic food animals are seldom documented, particularly in Asia. Here, Schar et al. review 749 point prevalence surveys, describing AMR trends in Asian aquaculture and fisheries over two decades, and identifying resistance hotspots as well as regions that would benefit most from future surveillance efforts.