When we talk about the emergence of antibiotic resistance, two factors usually get the blame: the overuse of antibiotics in human medicine and in agriculture. In both cases, the drugs’ presence exert selective pressure on bacteria, encouraging them to develop or acquire resistance genes that will protect them.

But there’s another way that bacteria are exposed to antibiotics. It’s through wastewater: residues from antibiotic manufacturing, retail drugs dumped because they are expired or no longer needed, and sewage — because a percentage of the drugs we take (and give to animals) pass through our bodies unused, and also pass intact through municipal wastewater treatment when it exists.

I wrote about this a bit last September, just after this blog launched, in the context of how difficult it can be to get rid of prescription drugs that you no longer need or want. (Plea: Don’t flush them.) But a new paper in PLoS One underlines that this problem is much bigger than the bottles cluttering your medicine cabinet.

For several years, faculty from several universities in Sweden have been tracking the content of wastewater flowing into a river near Hyderabad in India, a city that is a center of generic drug manufacturing. (For a sense of how saturated the local environment is with pharma firms — more than 90 — check the map at right.) Previously, they had found levels of fluoroquinolones  high enough to kill fish and permeating drinking-water wells in villages. (For humans, the most familiar fluoroquinolone is Cipro.) For this paper, researchers looked specifically at bacteria living in parts of the river where that industrial pharma effluent is flowing, to see whether they were developing resistance in response to that exposure.

Answer: Oh, yeah. Using a method called “multiplexed massively parallel pyrosequencing” (which I love just saying out loud), the team analyzed the bacterial DNA and found it loaded with resistance genes that would confer protection to multiple classes of antibiotics: fluoroquinolones, aminoglycosides and sulfonilamides. At three sites downstream of the key wastewater plant that processes the effluent, known resistance genes accounted for 1.7% of all the DNA they analyzed. Along with those genes, they also found two previously unknown plasmids that contained genes conferring resistance to fluoroquinolones (qnrD) and sulfa drugs (sul2).

It’s important to say that the bacteria in the river that were harboring these resistance genes were not disease-causing bacteria. It’s also important to say that is only minimally relevant. Once resistance factors arise, they move with surprising speed between bacteria and also across bacterial species. In the downstream samples, they also found abundant integrons and transposons that would allow the genes to move, reinforcing the case that resistance was evolving at these spots because of the antibiotic-laden effluent.

This Indian river is a hot spot because of the concentration of manufacturing along it — but it’s not the only offender. Last year, Chinese scientists reported on very high levels of oxytetracycline stimulating bacterial resistance in a river in China. In January, British scientists reported similar results for a river in Cuba. And as I said last fall, the US Geological Survey has found pharmaceutical residues in 80% of the 139 US streams they sampled in 2002.

National and international health agencies, and medical societies and NGOs, have programs that seek to reduce the overuse of antibiotics in human medicine. There’s increasing pressure, as we talk about here all the time, to push back against the overuse of antibiotics in farming. But the thought that antibiotics are spreading freely in groundwater, lakes and rivers is truly disturbing. Curbing that will require a whole different level of effort.

Cite: Kristiansson E, Fick J, Janzon A et al. 2011 Pyrosequencing of Antibiotic-Contaminated River Sediments Reveals High Levels of Resistance and Gene Transfer Elements. PLoS ONE 6(2): e17038. doi:10.1371/journal.pone.0017038

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