Author: Sam Linsen

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Antibiotic of the week: Norfloxacin

Antibiotic Pollution Index: 273 ( 29 September 2017)
What is the Antibiotic Pollution Index?

What it does
Bacterial cell division is an important feature of developing, or maintaining, an (infectious) bacterial population. Norfloxacin binds the bacterial DNA replication machinery and thereby prevents cell division. This leads to cell death in many different types of bacteria, as it is a broad-spectrum antibiotic.

Who gets it
Norfloxacin is used to treat urinary tract, prostate and kidney infections, infections of the gastrointestinal tract, as well as some sexual transmitted diseases. The clinical usage is becoming more restricted because of better alternatives. Namely, norfloxacin has rare but serious side effects such as rupture of the tendons and secondary infections, such as C. difficile, causing a high-risk bowel disease.

Where may it be produced?
India, Italy, Slovenia, Japan, Spain, China, USA.

And, SquaredAnt, does it pollute?
For a not-so-popular drug in the medical domain, norfloxacin pollution is suspiciously widespread. SquaredAnt found reports of norfloxacin pollution in China, UK, Spain, Poland, Japan, Canada, Australia and India. Norfloxacin has also been reported in food. In in Brazil, 15% of milk samples carry residues of this antibiotic (2017). One Nigerian study showed average of 0.173 microgram per gram beef – a nearly therapeutic concentration (2015). In Saudi Arabia, levels 1 microgram per gram in Chicken meat and liver have been reported (2000).

Warning lights
Most reports on norfloxacin date from the beginning of this century, when high resistance rates in Campylobacter and Escherichia coli bacteria became apparent. Merck, the sole producer of medical norfloxacin tablets, seized its production in 2014. In summary, we could conclude that phasing out this drug from the medical domain is already under way.

Any common sense in this antibiotic?
Has the medical field lost interest in this drug, and has this provided veterinarians with a carte blanche for norfloxacin use? The widespread pollution could point into this direction. Furthermore, for the publicly available Maximum Residue Level (MRL) lists that SquaredAnt could locate, none of these includes norfloxacin (an MRL would invoke a systematic monitoring of norfloxacin in food products of animal origin). Separating the medical applications from other usages is wishful thinking. For instance, E. coli that are resistant to norfloxacin often are resistant to related antibiotics as well. In other words, resistance caused by norfloxacin pollution could affect the medical domain indirectly. It would make sense to restrict the pollution of norfloxacin in order to prevent these and other toxicological consequences.

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Antibiotic of the week: Metronidazole

Antibiotics Pollution Index: 400 (11 September 2017)
What is the Antibiotics Pollution Index?

What it does
Metronidazole gets activated in cells that live in oxygen-low environments, known as anaerobic cells. It is effective against many anaerobic organisms, which include bacteria and parasites. It binds DNA, and causes breaks which cells do not survive.
Due to activation in an oxygen-low environment, this drug separates anaerobic cells from the patient’s own aerobic (oxygen-breathing) cells. Metronidazole use, however, increases the risk for cancer, which may be the result of activation in human cells, too. When received in high doses, this drug can also be neurotoxic.

Who gets it
An infamous target for metronidazole is Clostridium difficile, a typical landmark for bad hygiene and incorrect antibiotic use, leading to diarrhea, colon perforation, with a potential fatal outcome. It is also administered to prevent surgery-related infections and sexually transmitted diseases. Not only people are treated. This carcinogenic antibiotic is a frequently used drug in animal husbandry and aquaculture. It has been banned in the USA and Europe for food-producing animals, but big and small pets (such as horses, dogs, ornamental fish and reptiles) still receive it. Outside the EU and USA, you may find your metronidazole in your food, too: it is given to poultry, pigs, and fish. In all animals studied, this antibiotic remains detectable in many organs up to 2-3 weeks after the last dosage. This is 2 weeks short of the complete life of your average meat-chick.

Where may it be produced?
Poland, India, Italy, Portugal, China, Mexico, USA, France.

And, SquaredAnt, does it pollute?
We found evidence for pollution in WWT effluent, hospital effluent and river water. The concentration in WWT effluents is around 0.1 ng/ml. 500 million liters of waste water would give you approximately one dosage of metronidazole, of which you’d probably need 4 in a day. Spectacular enough, this low concentration could trigger resistance against metronidazole. Given the usage in farms, hospitals and pets throughout the world, there are probably quite a few places oxygen-low places -such as sewage systems and lagoons -where metronidazole pollution stimulates resistance on the long term.

Warning lights
The high cost of appropriate tests for infections and the seriousness of anaerobic infections has lead to an overuse of usage and an under-reporting of resistance against metronidazole.  But let’s give patients and doctors the benefit of the doubt. A more worrying signal is our finding that the on-line demand of this drug is very high. For those who ignore resistance, oncogenic and neurotoxic risks, metronidazole may seem like a wonder drug that can compensate bad hygiene and poor maintenance in stables, ponds, terrariums, etc.

Any common sense in this antibiotic?
Since 2 decades, metronidazole has been banned from food producing animals in the USA (1994) and the EU (1998). From 2017, authorities in China have introduced a standard to test for metronidazole in food. This indicates at the very least that metronidazole pollution is on the radar in China.

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Antibiotic of the week: Cefotaxime

Antibiotic pollution index: 236 (11 September 2017)
What is the Antibiotic Pollution Index?

What it does
The cell wall separates the bacterial cell from its surroundings, gives it strength and protection. With cefotaxime, cell walls break and bacteria die.

Who gets it
Cefotaxime is used to treat a wide range of infections, such as pneumonia, meningitis, abdominal infections and joint infections. It is a typical broad spectrum antibiotic: many bacteria dislike it. Veterinarians, however, do like it. Cefotaxime is used to treat pets and small farm animals worldwide, and cattle and pigs in a number of countries.

Where may it be produced?
India, China, Korea, USA, Italy, Germany.

And, SquaredAnt, does it pollute?
It may very well be. We found evidence for pollution in Spain and the United Kingdom, from hospital waste, waste water treatment effluents, and river water. All concentrations lie around 0.1 ng/ml. This means: if a course of cefotaxime would be be 2 gram per day, you would have to drink 20,000,000 liter if you’d like to recycle from river water directly. A daunting task, but hey, what doesn’t kill you makes you stronger!

Warning lights
If antibiotics concentrations are too low to kill bacteria, bacteria may start to allow this antibiotic in their daily lives at higher concentrations. What doesn’t kill them, makes them stronger… we call this “Antibiotic Resistance”, but the term could be “Antibiotic Ignorance” too. Resistance gives the impression of combat, that bacteria struggle to survive, that some day, resistance may be broken. But in many cases, bacteria don’t fight. For resistant bacteria, the antibiotic has become one of the many chemicals they simply deal with. From their perspective, the antibiotic is not even an antibiotic any more. They changed the lock, got a new key, end of story.
Antibiotic resistance (or should I say “ignorance”) against cefotaxime is on the rise everywhere. Portuguese rivers, American fruits an Indian dairy, they all contain bacteria that are perfectly fine to be exposed to cefotaxime.

Any common sense in this antibiotic?
No. Cefotaxime is a very powerful antibiotic to treat serious human diseases. But for now, treating pets, poultry, pigs and other animals with cefotaxime, which leads to a noticeable release into the environment as well as a rise in antibiotic resistance, is incompatible with a common sense strategy that reserves this drug for patients in need.

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