Category: Antibiotic of the week

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Antibiotic of the week: Trimethoprim

Antibiotic Pollution Index: 471 (12 October 2017)
What is the Antibiotic Pollution Index?

What it does
This drug blocks the propagation of bacteria, by interfering with folic acid synthesis. Folic acid is important for a number of processes, one of which is building up DNA. With trimethoprim, the bacterial cell number cannot increase, because DNA cannot be synthesized. It is often given in combination with a sulfonamide drug, acting jointly on the same pathway and leading to death of the bacteria.

Who gets it
Trimethoprim is used clinically to treat many infections in the urinary tract, skin, gastrointestinal tract, ear and respiratory tract. It is also used in the meat and fish industries: in 2008, more than 10 metric tons per year in the UK alone, accounting for over 80% of the total trimethoprim usage there. In Europe, it is used to treat and prevent respiratory infections after a disease has been diagnosed in a herd (pigs) or flock (poultry). It is used to treat big and small pets as well. Treated chickens accumulate high amounts in eggs (up to thousands of ng/g), which only diminshes after 10-20 days. It seems unlikely that such a long withdrawal time is respected in the present-day bio-industry, where, if a disease occurs, whole flocks are treated via drinking water. If this is indeed the case, poultry treatment could lead to residue in eggs, each egg containing ~1/1000 of a typical patient dosage. And cooking won’t help: trimethoprim is stable up to 200 degrees Celsius.

Where may it be produced?
Cyprus, Republic of Korea, Italy, Brazil, China, India, Spain, USA, Israel, Germany.

And, SquaredAnt, does it pollute?
We found evidence for pollution on 25 places around the world, including Europe, the USA, Asia, and Australia, in different types of waste and surface water. Concentrations are generally less then 0.1 ng/ml, with few exceptions. Even in possibly the global antibiotic pollution hotspot -Hyderabad, India-, the pollution does not exceed 4.4 ng/ml – quite a difference from the 14000 ng/ml that was reported there for ciprofloxacin. But don’t get your vision blurred by rankings: polluting less doesn’t mean that you don’t pollute. The predicted concentration for selecting resistant bacteria is 0.5 ng/ml. A wide-spread pollution in water may indicate that there are many sources, with potentially higher concentrations.

Warning lights
Overuse quickly leads to antibiotic resistance against trimethoprim, and this resistance is there to stay. For instance, already in the 1970s, up to 40% of inpatients carried resistance against trimethoprim in Turku, Finland. Elsewhere, resistance levels up to 65% are reported. And there is no quick fix. When Kronoberg County, Sweden, intervened to drastically reduce the local clinical trimethoprim usage for 2 years, resistance levels reduced only marginally, and returned to baseline level shortly after the intervention.

Any common sense in this antibiotic?
At least, in Europe and the USA, the veterinary use of trimethoprim has been restricted to animals in a herd or flock where a disease has occurred. Furthermore, health systems sometimes interfere to reduce trimethoprim usage. However, most measures to reduce trimethoprim usage are local, theoretical, or lead to compensation (=overuse) of another antibiotic. If no-one is connecting the dots, the world may lose this essential drug.

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Antibiotic of the week: Sulfadimidine or Sulfamethazine

Antibiotic Pollution Index: 296 (12 October 2017)
What is the Antibiotic Pollution Index?

What it does
This drug blocks the propagation of bacteria, by interfering with folic acid synthesis. Folic acid is important for a number of processes, one of which is building up DNA. It is a broad spectrum, synthetic antibacterial drug.

Who gets it
Sulfadimidine or Sulfamethazine (both refer to the same antibiotic) is often fed to or mixed in drinking water of pigs, cattle, poultry and fish, to prevent disease in crowded farms and fisheries. This drug is also used as a growth promotor in the meat production. However, for sulfadimidine, no lab-based evidence for growth promotion has been found, with the exception of one organ: the thyroid gland. This gland produces a hormone that regulates growth. But a bigger gland does not necessarily lead to a hormone boost. In fact, pigs and rats that get high sulfadimidine dosages are more lean. Even worse, enlargement of the thyroid gland has been described as an oncogenic effect of the drug. In earlier days, sulfadimidine was also approved for medical use, but this has been discontinued in most countries.

Where may it be produced?
US, China, Czech Republic, the Netherlands, Poland.

And, SquaredAnt, does it pollute?
Sulfadimidine or Sulfamethazine is produced in enormous amounts: in China, one factory alone claims a production capacity of 1000 metric tons a month. This would yearly amount to ~12% of the lower estimate of the annual worldwide use of all antibiotics combined (100.000-200.000 metric tons). Pollution has been observed in China, Thailand, Canada and the US, with highest concentrations in agriculture soil and agriculture waste water.

Warning lights
Sulfadimidine pollution has not only sparked antibiotic resistance, but even more so, some bacteria have adopted this antibiotic as a nutrient source. In soy crop fields in Canada, where high dosages of sulfadimidine were put into the soil to study the effect of antibiotic residue in fertilizer, a microbacterium bacteria species started to use sulfadimidine as a carbon source. Translated to humans: they got shot at, warded off the bullets, and built a steel mill with it. We created a monster…. today in your fields, tomorrow in your guts.

Any common sense in this antibiotic?
Concerns related to sulfadimidine use in agriculture have already been raised many years ago. Reasons were potential health risks and the high number of non-compliant farms. In 1989, sulfadimidine was almost withdrawn from the US industry. The New York Times News Service reported that “The long regulatory history of sulfamethazine is the latest illustration of the difficulty federal agencies are having in untangling the web of scientific, political and economic issues before toxic substances can be eliminated from the food supply.” The withdrawal never took place. Non-compliance and conflicts of interests continue until today, throughout the world. Common sense is hard to find.

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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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