Drug-Resistant Bacteria: To Humans From Farms via Food

You have to love a scientific commentary that starts this in-your-face:

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, responding to a Food and Drug Administration (FDA) guidance document advising against the sub-therapeutic use of antibiotics in livestock.

Well, here’s some.

To be clear: That’s the paper’s language, not mine. The gut-punch challenge comes from an editorial that is only on the web so far but is scheduled for publication in the journal Clinical Microbiology and Infection. It accompanies a research article that makes an important claim:

Chickens, chicken meat and humans in the Netherlands are carrying identical, highly drug-resistant E. coli — resistance that is apparently moving from poultry raised with antibiotics, to humans, via food.

For anyone who thinks about these issues — anyone interested in sustainability, organics or small-scale farming, anyone working to combat foodborne disease — this may seem like a foregone conclusion. And it should. The first observation that giving antibiotics to animals spreads antibiotic-resistant bacteria to humans was made in 1976, and there has been a steady accumulation of evidence since. Nevertheless, the argument keeps being made that the connection is not water-tight , and that antibiotic use outside agriculture — in human medicine, perhaps — can be blamed for the vast rise in antibiotic resistance.

For those who don’t want to believe in this connection — and it is, at this point, a matter of belief much more than it is of evidence — this new paper too may not convince them. To me, though, it’s more good evidence that overuse of antibiotics in farming is a human-health threat.

The details:

A public-private team from the Netherlands (several universities and the National Institute for Public Health and the Environment) gathered samples of E. coli, the ubiquitous gut bug, from live poultry and from retail chicken meat. They looked for a particular resistance pattern: extended-spectrum beta-lactamase resistance, or ESBL.

ESBL is an emerging problem in human medicine. It tends to appear in Gram-negative bacteria such as E. coli and also Klebsiella, species that cause hospital-acquired infections in vulnerable people such as ICU and burn patients. ESBL confers protection against whole families of drugs, starting with penicillin and extending to the later generations of cephalosporins, and leaves bacteria treatable by only one remaining small family of drugs, the carbapenems.

ESBL incidence has been rising steadily for the past two decades, even in countries in the European Union where human antibiotic use is strictly controlled by government policy — meaning there are not a lot of antibiotics washing around, exerting the selective pressure that drives the emergence of resistance.

Microbiologists have been curious how that might be. They have started to look closely at whether antibiotic use in livestock is stimulating ESBL resistance instead, and they have made provocative findings. In the Netherlands, for instance — which has conservative human antibiotic use, but the most liberal agricultural antibiotic use of any EU member — the percentage of E. coli that was found in the guts of chickens and was carrying ESBL went up five times over between 2003 and 2008.

So, in this new study, researchers looked for ESBL-containing E. coli in bacterial samples taken from chickens and stored in a vast national database, and also from 98 chicken breasts that they purchased from 9 stores and 3 independent butchers. They analyzed the E. coli for the presence of ESBL genes, and plasmids — mobile loops of DNA that move between bacteria — containing those genes. They weren’t difficult to find, either: Of the 98 chicken-meat samples, 92 contained at least one ESBL.

Then, in a second step, the researchers plumbed a different national database, of resistant bacteria found in humans. They looked for ESBL-containing E. coli, analyzed the genes and plasmids, and then looked for matches between the human genes, plasmids and bacterial strains and the ones they had already  found in poultry. Did they find them? Why, yes, they did.

In a representative sample of human ESBL-positive E. coli isolates in the Netherlands, 35% contained ESBL genes and 19% contained ESBL-genes located on plasmids that were genetically indistinguishable from those obtained in poultry isolates … Furthermore, 94% of a representative sample of chicken meat was contaminated with ESBL-producing E. coli of which 39% belonged to genotypes also found in human samples.

Note: The human isolates were in that national database because the humans from whom they came were sick, hospitalized with drug-resistant urinary tract infections and bloodstream infections. The ESBL-containing E. coli hadn’t caused visible illness in the chickens, but it had affected the humans it spread to.

The criticism of this paper is likely to be the same as always: that the case has not been proven on an individual level. That is, no one has given antibiotics to a single chicken, identified the development of resistance in that chicken, traced the spread of resistant organisms from the chicken (into its manure and thus into the environment, and into its flesh at slaughter and thus into the retail chain), prospectively identified a single free-living human whom that now resistant organism is going to affect, and monitored the development of illness in that human.

No one would do that experiment: It’s impossible to construct experimentally and wouldn’t be ethical if you tried. But no one needs to. The case has been proven on the population level: populations of chickens, collections of chicken meat, populations of humans. If you look at the 30 years of research on this question, it’s been proven time and time again.

Cites: Leverstein-van Hall, MA et al. Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains. Clinical Microbiology and Infection. Accepted article, http://dx.doi.org/10.1111/j.1469-0691.2011.03497.x; Pappas, G. An Animal Farm Called ESBL: Antimicrobial resistance as a zoonosis. Clinical Microbiology and Infection. Accepted article, http://dx.doi.org/10.1111/j.1469-0691.2011.03498.x.



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