Out of Africa, out of this world: the miraculous story of E.bugandensis

What does a Space-X or Soyuz capsule carry as cargo to and from the International Space Station (ISS)? In 2015 and 2016, among the freeze-dried apple slices, it included kits to collect bacteria and send them back to Earth. The goal was to study which bacteria inhabit ISS, on the dining table, hygiene compartment, the permanent multipurpose module, and other places. And to uncover their antibiotic resistance patterns. Nearly 60 strains of microbes where identified. Antibiotic resistance was found against penicillin (92 %), oxacillin (68%), rifampin (66 %), erythromycin (64%), cefoxitin (49%), cefazolin (29%), tobramycin (19% ), and gentamicin and ciprofloxacin (14%) (these were all the drugs tested). The most resistant species was the bacterium E. bugandensis: with the exception of 2 strains sensitive to tobramycin, all six isolates from ISS were resistant to all 9 antibiotics.

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Antibiotic of the week: Chloramphenicol

Antibiotic Pollution Index: 731 (19 November 2017)
What is the Antibiotic Pollution Index?

What it does
Chloramphenicol blocks the production of proteins in bacteria. When protein production is delayed, the bacterial cell stops to grow.

Who gets it
Chloramphenicol is a broad-spectrum antibiotic that is used to treat a large number of infectious diseases. Given a number of serious side effects, most physicians look for alternatives first before prescribing this drug, and in some countries it has been banned from the clinic. For instance, this drug has been linked to bone marrow damage, leading to anemia and potentially childhood leukemia. When risk groups are avoided or when the disease is life threatening, chloramphenicol is, however, an important drug: in regions with less sophisticated healthcare systems, it is used to treat meningitis, typhoid fever, plague and cholera.

The drug, although practically banned from medical use and meat production in many countries, is not reserved for people in need alone. It is still used for non-food producing animals around the world, and seafood production in Asia has become notorious for chloramphenicol pollution. Recently, this drug was seen in pharmacies that sell to fish and shrimp farms in Vietnam; and  Chinese authorities found chemical traces in 9% of seafood found in restaurants in some major cities, including chloramphenicol.

Production and trade
It may be produced in India, Hungary, China, Japan, USA, Spain, Italy.
In 2016, Top-3 importers were Venezuela, Chile and the Netherlands; exporters were China, the Netherlands and India.

And, SquaredAnt, does it pollute?
18 Sites with environmental chloramphenicol residue in our database reside in Nigeria (waste water, river water and sludge) and Tianjin, China (agriculture soil). Especially in Nigeria, the concentrations are fairly high, up to ~100 ng/ml in sludge. Probably, this is due to a combination of medical and veterinary use, too: for instance, observations in 2012 showed that chloramphenicol has been routinely used in poultry farming in Nigeria.
The bacterium that produces chloramphenicol can be present in soil. Therefore it may be not as straightforward as it seems to distinguish polluting from naturally occurring trace amounts. A broad evaluation of historical land usage, irrigation sources and agricultural practices is crucial to rule out chemical pollution or its consequences (e.g. soil enrichment for chloramphenicol-producing bacteria).

Warning lights
Chloramphenicol was no popular drug, given a number of potentially serious toxic side effects. Whenever alternatives have become available, this drug has been phased out. In the recent years, it may have become more poplar, as a replacement for other antibiotics against which resistance has been developed. This is a warning light – not so much for chloramphenicol, but for the gravity of the overall AMR challenge. Increased usage of this antibiotic is probably an unsustainable solution in the longer term: chloramphenicol resistance genes have been detected on farms, and historical data shows that chloramphenicol resistance is common in places where it is used – and can extend to resistance against other antibiotics, too.

Any common sense in this antibiotic?
Chloramphenicol remains essential for treatment of life-threatening meningitis, typhoid fever, and other infections in developing countries. Chloramphenicol is slowly becoming a last resort drug, as a replacement for other, originally safer, and more effective antibiotics that are now phased out due to antibiotic resistance. The importance of this drug will therefore grow, therefore tighter restrictions on its usage in food production are needed.

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Antibiotic of the week: Clarithromycin

Antibiotic Pollution Index: 203 (19 November 2017)
What is the Antibiotic Pollution Index?

What it does
Clarithromycin inhibits the synthesis of proteins in many different types of bacterial pathogens. It does so in some parasites as well, such the one responsible for toxoplasmosis.

Who gets it
Clarithromycin is used to treat lung, stomach and throat infections, and other infections of the gastrointestinal tract, respiratory tract, or skin. In case of pregnancy, this drug should be taken only when absolutely necessary, as it slightly increases the risk for a miscarriage. When it entered the market, its efficacy against Mycobacterium Avium Complex (MAC), a lethal lung infection in patients with a defect immune system, had a great impact among carriers of HIV – not the least because the industry delayed market entrance in the US for economic reasons. It is a popular drug: it is highly consumed, for instance, in Canada it ranked second after amoxicillin in 2014. Resistance level are, however, fairly high as well. In Asia, resistance levels in S.pneumonia   reached 80% in the beginning of this century. In Canada, 22% was resistant in 2014, the highest rate of all antibiotics in this pathogen. Worldwide, it may be used in food animals, but clarithromycin’s ancestor, tetracycline, is more abundantly used. There seems nevertheless a noticeable interest of pet-owners to purchase this drug on-line.

Where may it be produced?
India, Japan, USA, Saudi Arabia, Spain, Mexico, China, Germany, Malaysia, Israel.

And, SquaredAnt, does it pollute?
There is evidence for trace amounts in the environment in Germany, the UK, and Canada; in Spain, the concentration tends to be substantial, up to 1 ng/ml in hospital waste water and o.5 ng/ml in Waste Water Treatment effluents. Such values are well above  the predicted concentration that leads to resistance, which is 0.25 ng/ml.

Warning lights
Anno 2017, a clear warning light comes from the Helicobacter pylori community, that has to deal with a bacterium that infects half of the worlds population, causes ulcers in 10% of these carriers and is strongly linked to cancer in the stomach (1-3% of people infected develop stomach cancer, a disease that causes 700.000 deaths per year worldwide). Whereas billions of people are only carriers, the infection can become symptomatic with grave consequences when left untreated. H.pylori infections are often treated with a cocktail of drugs, and clarithromycin is usually among these. Despite a sharp increase in resistance rates in H.pylori (from 5% to 50% from 1993 to 2013), there is no alternative for clarithromycin in the drug cocktail. This leads to desperation, as reflected by the following quote: “The problem with this critical role [of Clarithromycin] is that antimicrobial resistance to this drug is sharply increasing and our hopes to have successful eradication regimens (i.e., consistent treatment success > 90%) including the clarithromycin is unfortunately falling.”

Any common sense in this antibiotic?
Clarithromycin is an essential drug according to the WHO and indispensable for H.pylori treatment. Furthermore, this drug is popular and used for many other infections too, for human disease and in animals as well. Resistance against this drug is increasing. Once resistance occurs to clarithromycin, resistance to other important antibiotics such as erythromycin occurs as well, and vice versa. More restricted use of clarithromycin and its related drugs, especially in the veterinarian domain, could safeguard its efficacy in human disease.

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