An animal farm called extended-spectrum beta-lactamase: antimicrobial resistance as a zoonosis

Authors


‘Show us the science that use of antibiotics in animal production is causing this antibiotic resistance,’ Dave Warner of the National Pork Council told the Washington Post back in June 2010 [1], responding to a Food and Drug Administration (FDA) guidance document advising against the sub-therapeutic use of antibiotics in livestock.

Well, here’s some.

The FDA guidance document rapidly became a subject of political debate, criticized not only by the meat industry, as cited above, but also by worried scientists for being a hesitant belated step in an important subject that the European Union has dealt with since 2006. The political nature of the issue extended to PAMTA, (Preservation of Antibiotics for Medical Treatment Act), a legislation attempt that has been at present unfortunate.

Antibiotics have been used in the animal-raising industry for decades, for three reasons: (i) therapeutically, (ii) preventively (when symptoms of disease emerge in a minority of animals raised crowded in thousands in a secluded environment, all animals are treated) and, most controversially, (iii) as growth promoters: added to the food or water of these animals, at low, but protractedly administered, doses to enhance feed efficiency and produce larger animals faster and with less food. It has been estimated that at least 30% of the total annual antibiotic use (although others raise this percentage to > 70%) is for sub-therapeutic purposes [2]. The ensuing selective pressure leads to the development of antibiotic-resistance genes, for example extended-spectrum beta-lactamase (ESBL), which can then be shed in the environment, directly through the food chain, by direct contact, or through contamination of the water horizon and fields from animal waste. A pioneering study by Levy et al. in 1976 [3] demonstrated that tetracycline resistance, and subsequently multiple-drug resistance, developed in poultry farms where tetracycline was used as a growth promoter (but not, or at least to a lesser extent and belatedly, in farms where antibiotic additives were not used) and spread to the workers of these farms and their families (but not to unrelated households of the same area). Since then, the recognition of the presence of ESBL in poultry and pig farms and in retail meat has been increasingly recognized in diverse world regions, including Asia, the USA and Europe [4–6]. Furthermore, it has been demonstrated that ESBLs of zoonotic origin are similar to those causing clinically significant community-acquired antibiotic-resistant infections. There has also been increasing concern about the importation of antibiotic resistance through retail meat products, as for example in the UK, where imported retail chicken harbours the CTX-M-2 gene, which is not indigenous in clinical terms [7], or in Denmark (a country that was one of the first, along with Sweden, to abolish the sub-therapeutic use of antibiotics in such settings), where meat imported from Germany was incriminated [8].

This situation goes beyond Escherichia coli. It has been increasingly recognized in Salmonella spp. [9], Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus [10], and typically for Enterococcus faecium: the use of the glycopeptide avoparcin as an additive in the past was directly correlated to the emergence of glycopeptide-resistant Enterococcus faecium in the community, a situation that reversed upon the institution of regulations against avoparcin use [11].

However, is there direct evidence of the, at least partial, zoonotic nature of ESBL and of antibiotic resistance in general? Taking into account the substantial financial burden that antibiotic abolition would bring to the industry (ranging down to individual farms), evidence should spread beyond epidemiological observations. Enterococcus faecium resistance patterns offer some evidence, with the emergence of streptogramin resistance, which cannot be attributed to extensive antibiotic use in humans but can be attributed to the use of virginiamycin as a growth promoter. The study by Leverstein-van Hall and colleagues in the present issue of Clinical Microbiology and Infection offers further evidence. The authors not only successfully identified ‘fingerprints’ of animal origin ESBL in human disease E. coli isolates, but further quantified the burden of disease induced by zoonotic resistant species: which was 2–16 patients in the Netherlands in a period of 3 months. Extrapolating these results to annual cases in a wider geographic region underlines the magnitude of the problem and renders any financially related debate useless, as the Danish experience has already shown: subsequent to prohibition of the sub-therapeutic use of antibiotics, the Danish meat industry flourished, instead of exhibiting losses [2]. Back to politics then, and in need of stern, brave decisions.

Transparency Declaration

Conflicts of interest: nothing to declare.

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