Appearance of β-lactam resistance genes in agricultural soils and clinical isolates over the 20th century

Debate exists about whether agricultural versus medical antibiotic use primarily drives increasing antibiotic resistance (AR) across nature. Both sectors have been historically inconsistent at antibiotic stewardship and, as a result, acquired bacterial AR has progressively increased over the 20th century. The question is which sector has most influenced changes in acquired AR. To examine this question, we quantified four broad spectrum β-lactam AR (ARG; blaTEM, blaSHV, blaOXA and blaCTX-M) and class 1 integron genes (int1) in soils archived since 1894 from Askov Experimental Station, Denmark. ARG levels were significantly higher in post-1940 soils that only received manure (M) versus inorganic fertilisers (IF) (paired-t test; p < 0.001). However, first appearance of each ARG varied over historic time; blaTEM and blaSHV between 1963 and 1974, blaOXA slightly later, and blaCTX-M in 1989, dates that parallel appearance of each ARG in hospital isolates, suggesting their parallel occurrence in animal manure and human patients. It is not possible to determine whether farm versus hospital AR appeared first, but archive data imply they are mutually influential. Interestingly, levels of β-lactam ARGs in the M soils, especially blaCTX-M, declined since the mid-1990s, which aligns with reduced non-therapeutic antibiotic use in Danish agriculture. These data suggest improved antibiotic stewardship can reduce soil ARG reservoirs, although it also shows reduced manure applications to agricultural soils should be included in prudent stewardship programmes