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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