Orgies and antibiotic resistance

When a small body of water, say a slow flowing creek or water in a drainage ditch, "goes septic" it starts to stink, often giving off a rotten egg odor (hydrogen sulfide, H2S). This isn't a sign that the water is polluted in the chemical sense of toxic materials. It means that so much organic matter has entered the water that the bacteria there have gone on a food orgy. The initial gluttons are aerobic bugs that need oxygen as a final electron acceptor to generate energy for their needs. When the feasting aerobes use up all the oxygen they die and are replaced by a new set of diners, the anaerobes. These guys can keep eating even without oxygen because they know how to use another common electron acceptor, sulfates, turning them into H2S. Hence the stink. The reason stagnant pools or slow running streams are most at risk when we discharge a lot of "edible" organic matter (like sewage) into them is because they don't get re-aerated faster than the oxygen is being used up. Fast moving streams or artificial aeration is one way to solve that problem and also break down all the organic junk we dump into them.

That's exactly how a conventional sewage treatment plant works. It's loaded with bugs that eat organic material and also supplied with plenty of oxygen. In fact it's set-up to make these beneficial bugs as happy as possible so they can keep eating and eating and eating. Now a new study from the University of Michigan suggests that it isn't only the good bugs that are happy in a conventional treatment plant but the bad ones, too (hat tip reader rustyjewell). They not only eat well but they have sex (of a sort), exchanging genetic material. The result is a gradual enrichment in certain kinds of antibiotic resistant bacteria as they move through the treatment plant:

“Wastewater treatment plants are most effective at treating sewage when they have conditions that allow beneficial bacteria to thrive and improve the quality of the water,” said Karen Kidd, a University of New Brunswick ecotoxicologist familiar with the study.

“However, this study indicates that these conditions can also favor the mutation of some and act as a source of antibiotic resistant bacteria to the environment.” (Andrew McGlashen, Environmental Health News)

The work was done in the lab of University of Michigan microbiologist Chuanwu Xi. Chuanwu and her team collected 366 species of the bacterial species, Acinetobacter, from a treatment plant in Ann Arbor, MI. Antibiotic resistant Acinetobacter isn't as notorious as methicillin resistant Staph aureus ("MRSA") but the species A. baumannii is a really bad actor in hospitals, especially (but not only) among wounded Iraq and Afghanistan veterans (see earlier posts here, here). They followed the Acinetobacter through three stages in the treatment plant (raw influent, second effluent, final effluent) and two in the receiving water, Huron River (upstream and downstream of the plant discharge). Along the way they tested the Acinetobacter for resistance to 8 different antibiotics: amoxicillin/clavulanic acid (AMC), chloramphenicol (CHL), ciprofloxacin (CIP), colistin (CL), gentamicin (GM), rifampin (RA), sulfisoxazole (SU), and trimethoprim (TMP). If you've taken antibiotics recently, chances are you'll see its name on this list. Results?

The prevalence of antibiotic resistance in Acinetobacter isolates to AMC, CHL, RA, and multi-drug (three antibiotics or more) significantly increased (p < 0.01) from the raw influent samples (AMC, 8.7%; CHL, 25.2%; RA, 63.1%; multi-drug, 33.0%) to the final effluent samples (AMC, 37.9%; CHL, 69.0%; RA, 84.5%; multi-drug, 72.4%), and was significantly higher (p < 0.05) in the downstream samples (AMC, 25.8%; CHL, 48.4%; RA, 85.5%; multi-drug, 56.5%) than in the upstream samples (AMC, 9.5%; CHL, 27.0%; RA, 65.1%; multi-drug, 28.6%). (Yongli Zhanga et al., "Wastewater treatment contributes to selective increase of antibiotic resistance among Acinetobacter spp.," Sci. Tot. Env. [abstr.])

What this shows is that resistance to some commonly used antibiotics ramped up fast as the bugs traversed the plant, and while the disinfection of effluent as it was discharged killed most of them, the ones that got through were significantly enriched in antibiotic resistance.

While disquieting, a little reflection suggests this isn't so surprising after all. The antibiotics you take for medical reasons are often not much changed by the time you eliminate them from your body through the sewer system. Add to that the antibiotics from farm run-off in operations that use antibiotics for poultry or cattle and you have a recipe for promoting resistance. The optimal conditions in the treatment plant may also encourage selection. Moreover even without mutation, there are always resistant bacteria around and in the happy confines of the specially engineered microbiological orgy that is a treatment plant there is plenty of opportunity of bacteria to share genes.

One obvious thing to do is decrease antibiotic use, especially for non medical reasons like agriculture. But another would be alter treatment plants so that their effluent is less likely to have live bacteria of any kind. That's a fairly expensive proposition, but maybe somebody will come up with a cheap way to sterilize effluent sufficiently for environmental purposes.

Antibiotic resistance is a major public health problem. Time to find out more how much conventional sewage treatment plants are contributing.

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So would this system be considered "conventional"? The water is well oxygenated. If I'm understanding this correctly (and I'm not at all sure I do), everything, from going out behind a bush to the slickest, high-tech sewage treatment plant, can be a breeding ground for the bacteria.

CC: Yes, this would be considered a conventional secondary treatment plant. Primary treatment is physical: screening out the big stuff (guns, baseball bats, etc.); secondary is biological, like this one; tertiary are a heterogeneous assortment of more expensive, advanced or specialized treatment processes like reverse osmosis or activated carbon. It doesn't matter if the bacteria grow in the treatment plant (they have to grow for the process to work). What matters is what is in the effluent. This is usually disinfected to some degree, but that process isn't 100%. Once resistant bugs are out there, they can grow and find a niche.

I can not see a solution to this one without a revolution in sewage treatment systems.
If you are going to contain human effluent and try and break it down using bacteria I see no way to prevent an increase in anti-biotic resistance. By definition it is human effluent so is going to include a higher level of antibiotics used in humans than the water course more generally. Given that then you have a high density of various bacteria reproducing rapidly in a relatively concentrated, but not lethal, antibiotic cocktail. Any pre-existing resistance is going to be selected for as will novel emergences or resistance via gene swaps. Given the inevitability of emergence the only remaining option is complete sterilisation of the effluent, which must be nigh on impossible given the volumes, even if small amounts remain they will be introducing more, and novel, anti-biotic mutations into the gene pool. The remaining options are to reduce the concentration of antibiotics by further dilution, reduced usage or reformulation to increase metabolic breakdown.
Did I forget anything obvious?

JJ: Depends on the place, I suppose. Use of composting toilets is one possibility, esp. or the developing world and water poor areas of the country. And it is possible that some kind of catalytic flow through or flow over surface might be an approach. The question is, how much does this contribute to antibiotic resistance in the environment?

Just a thought.

If you turn city sewage systems into hydro generators using methane...then the bacteria should be killed...as well as denaturation of hormones etc.

Notice that this wasn't a problem 50 years ago, when the human population was about half the present level.

Overpopulation leads to dependence on factory-farming, which in turn leads to dependence on antibiotics in food production.

Overpopulation leads to greater volumes of sewage, obviously, and therefore greater quantities of bacteria swapping genes in the sewage treatment plants and making their way into the environment.

And the root cause of overpopulation is the promulgation of religious dogmas against contraception.

See also your entry about the Catholic Church.

Minus the Pope, many of the world's problems would be that much easier to solve.

Unfortunatelly, it's true, that we overdose antibiotics. One of my friends, who is a student of medcine, once told me what they are taught: 'If you don't know what to prescribe - just prescribe an antibiotic'. That's terrible but we take multicoloured pills like candies. And when we really need them - they simply don't work.

By wybory sondaze… (not verified) on 20 Apr 2009 #permalink

"And it is possible that some kind of catalytic flow through or flow over surface might be an approach"

How does that work? Can it treat the kind of volumes we are dealing with and what % of the live might it reasonably be expected to eliminate?

In my other comment I said the sewage was human and so the higher concentrations would be in human antibiotics selecting for resistance to these. How about antibiotics used in animal husbandry? Would they be higher and if so why? Do they survive into our food chain and then into our sewage? If not I do not see why they should be concentrated in a sewage treatment plant. Would a similar problem be occurring in silage clamps or run off tanks on dairy or pig farms? How is farm effluent managed?

I am sorry about the number of questions but if anyone knows so of the answers and has time to post ...

"And the root cause of overpopulation is the promulgation of religious dogmas against contraception.

"See also your entry about the Catholic Church.

"Minus the Pope, many of the world's problems would be that much easier to solve."

A cursory look the relationship between national population growth rates and percent of population classified as Roman Catholic shows no correlation between the two. Are you suggesting that the Pope successfully discourages non-Catholics from using birth control? He sure doesn't have that effect on Catholics in Italy, Spain, France, the U.S. A., Canada, Lithuania, Croatia, Germany, etc.

(Also, I think it can be argued that there were reasons other than population size that antibiotic overuse was less of a problem in 1959 than now.)

There are good papers going back into the late 1960s that discuss the relationship between resistance development and sewage plants. But the story actually goes back to 1928 and the work of Fred Griffith. Griffith heat killed pathogens, mixed them with non-pathogens and saw lethality transferred to the non-pathogens. Thus, none of this is new. What is wrong here is that the regulatory community, especially EPA, has been and continues to be asleep at the switch. EPA will not discuss antibiotic resistance and sewage because if it did in a serious way that would adversely impact its fictional story of the benign impact of sewage sludge applied to America's farmland. The other impending issue is the use of reclaimed (recycled) water, again full of bacteria, some of which are resistant and some of which are potential pathogens. Again there are good papers discussing the failing of sewer plant manufactured reclaimed water to be protective of public health.

Then, as noted in the article there is the issue of oxygenation. High-pressure air is injected through numerous micro jets into the sewage to supply oxygen. But this creates a fog of aerosolized droplets that can drift long distances into the surrounding community. The same aerosol issue and pathogen drift problem arises from sprinkler applied reclaimed water, again there are good papers on this. None of this, however, is being studied in a comprehensive way by the regulatory community.

My group has been looking at these issues and we have run some preliminary lab tests on this reclaimed water (six California sewer plants producing certified recycled water thus far tested). All are passing through their systems chlorine resistant bacteria. That in and of itself is interesting because the human immune system depends on a chlorine-like material to kill pathogens when engulfed within phagocytes. What happens if these are chlorine resistant? But, it becomes more complicated because antimicrobials are becoming exhausted and the pharmaceutical industry is spending far less of new antibiotics. As the bugs become more resistant, at the same time our tools are diminished. There are bacteriostatic antibiotics, but these common drugs rely on a competent immune system---again, what if chlorine resistant? Then we have enhanced virulence by exposure to chlorine in water treatment, see for example the work of Matt Wook Chang on enhanced virulence from chlorine and MRSA to get some feel of this.

We ran reclaimed water produced by sewer plants under strict controls outlined by the State of California producing water that met state standards. As released at the plant and using PR lactose broth in Durham tubes, the results were 0/0/0. But that same water taken down the pipe at point of use showed 3/3/3---or numbers of bacteria technically off the chart. Thus we suspect a combination of viable but non-culturable and development of biofilms. Again, this is not being studied. It is not that this is some fluke or an unknown result, but the standards allow for it. This raises serious questions about how protective of public health these standards actually are. Again, there are numerous papers showing that water that met standards did not protect public health and that knowledge has also been around for decades----but why? The political lobby of sewer producers dose not want to deal with these issues, so the issues are buried.

By Dr Edo McGowan (not verified) on 23 Apr 2009 #permalink