In the long back and forth between science and agriculture over the source of antibiotic resistance in humans — Due to antibiotic overuse on farms, or in human medicine? — one question has been stubbornly hard to answer. If antibiotic-resistant bacteria do arise on farms, do they leave the farm and circulate in the wider world? And if they do, how much damage do they do?
A multi-national team of researchers recently published their answers to both questions. Their answer: In Europe, 1,518 deaths and 67,236 days in the hospital, every year, which would not otherwise have occurred.
Their argument (in the open-access journal Emerging Infectious Diseases, published by the US Centers for Disease Control and Prevention), builds on two earlier papers, both published in 2011. One estimated the additional deaths and hospital days incurred in Europe because of infections with drug-resistant staph and E. coli, without exploring the source of the resistance in those bacteria. The second analyzed the resistance genes in human E. coli infections, and compared them with resistance genes found in E. coli recovered from chicken meat being sold in stores (and found them similar to identical).
This new paper uses those pieces of research to create a formula. The terms in the formula are:
- How many illnesses and deaths occurred in the year 2007 as a result of E. coli carrying a specific resistance signature — to third-generation cephalosporins, which include the veterinary drug ceftiofur and the human-use compounds cefixime (for ear infections) and ceftriaxone (for gonorrhea);
- To what degree is there an overlap between third-generation cephalosporin resistance in E. coli (shortened to the acronym G3CREC) in humans and in chickens;
- What proportion of those G3CREC deaths and illnesses can therefore be linked to resistance carried by chickens and chicken meat, and arising from veterinary antibiotic use.
Their answers: In the Netherlands, where some of the earlier work was based and the data on farm antibiotic use is very good, 21 deaths and 908 extra hospital days. In England, 282 deaths and 12,500 extra hospital days. In Germany, 192 deaths and 8,500 extra hospital days; in Turkey, 444 deaths and 19,700 hospital days; and so on. (Their Technical Appendix giving their results in more detail is here.)
The authors say:
We already know that G3CREC is rapidly rising in many countries, and in Europe, the infection rate is likely to have tripled from 2007 to 2012. Globally, billions of chickens receive third-generation cephalosporins in ovo or as day-old chicks to treat E. coli infection, a practice that has resulted in large reservoirs of resistant bacteria. In Canada, this practice has been associated with substantial increases in resistance to third-generation cephalosporins in Salmonella enterica serovar Heidelberg isolates detected in humans. …
The number of avoidable deaths and the costs of health care potentially caused by third-generation cephalosporin use in food animals is staggering. Considering those factors, the ongoing use of these antimicrobial drugs in mass therapy and prophylaxis should be urgently examined and stopped, particularly in poultry, not only in Europe, but worldwide.
It’s important to note that the kind of cephalosporin use in eggs that’s described above was recently banned in the United States by the Food and Drug Administration. What’s not known at this point is whether the resistance that has already been created by long-term cephalosporin use will wither away because the antibiotics are no longer putting evolutionary pressure on bacteria — or whether it will persist, and continue to circulate, because that particular resistance DNA doesn’t cost bacteria anything to hold on to. In England, poultry producers recently agreed to a voluntary ban — but the British nonprofit the Soil Association has research which suggests other farm antibiotics may exert pressure to keep that resistance DNA In circulation.
The authors end their paper with a plea for better data on farm antibiotic use, so that the possible threat to people can be anticipated and predicted. It’s a common plea, and commonly frustrated; in both Europe and the US, agriculture has resisted calls for additional data (most recently in the refusal to mandate additional data-gathering during the reauthorization of the FDA project that gathers it).
Nevertheless, in a counter to this paper, the European ag-industry nonprofit the Responsible Use of Medicines in Agriculture Alliance maintains that the data used by the researchers is incorrect and doesn’t accord with how antibiotics are actually used in poultry production. Their statement, via the journal World Poultry, is here.
Cite: Collignon P, Aarestrup FM, Irwin R, McEwen S. Human deaths and third-generation cephalosporin use in poultry, Europe [letter]. Emerg Infect Dis. 2013 Aug. http://dx.doi.org/10.3201/eid1908.120681