Category: Antibiotic of the week

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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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Antibiotic of the week: Nalidixic acid

Antibiotic Pollution Index: 129 (19 November 2017)
What is the Antibiotic Pollution Index?

What it does
Nalidixic acid was discovered in 1962 and became the first antibiotic of the quinolone family. This family targets DNA synthesis in bacteria that leads to their death. Nalidixic acid mainly affects gram negative bacteria. Its successors, quinolones and fluoroquinolones drugs (such as norfloxacin), are less toxic and more effective against a broader spectrum of bacteria.

Who gets it
Nalidixic acid was commonly used to treat urinary tract infections, as it is rapidly secreted via the kidney and therefore reaches the urinary tract in a straightforward manner, both in humans as animals. These and other infections may be caused by food-borne pathogens such as Shigella, Salmonella and E. coli. Otherwise healthy individuals would be able to restore their own health, but dehydrated and/or undernourished children, elderly, and patients with a weak immune system, need medical treatment. In advanced healthcare systems, better alternatives are now available and this drug may be over its peak.

Where may it be produced?
Italy, India.

And, SquaredAnt, does it pollute?
We find minimal evidence for pollution of surface waters and waste effluents in Spain and in Australia. Concentrations tend to be low: the highest concentration is 0.06 ng/ml from a waste water treatment effluent in Spain. Or,  from 17 billion liters of water you can harvest one dosage of 1 gram. The environmental concerns related to this drug, so far, seem to be limited.

Warning lights
Many -but not all- types of resistance in the quinolone family include nalidixic acid resistance. As such, resistance against nalidixic acid may not be caused by nalidixic acid per se, and vice versa, resistance to other quinolone drugs may be caused by inadequate use of nalidixic acid. This is of importance when looking at resistance against this drug, which rose quickly after the turn of this century. In those years, in Germany, France, Spain, UK and Taiwan, an increase in the incidence of Salmonella strains that are resistant to nalidixic acid rose from ~5% to ~50% in humans and pigs. This occurred after the licensing of veterinary use of enrofloxacin and danloxacin, which belong to the same family as nalidixic acid. In 2004, resistance of Campylobacter bacteria against nalidixic acid in chicken and/or cattle throughout Europe reached 100%. An Australian study traced the origin of resistance against nalidixic acid in bacteria that cause enteric fever (Salmonella Typhi and Paratyphi). There, the share of resistant strains rose 70% in from 2009 to 2010. Most of these isolates came from India. Studies in the Shigella pathogens showed similar trends for Asian and African isolates. Summarized: nalidixic acid resistance itself is a warning light, very much a global phenomenon, and related to food production and food safety.

Any common sense in this antibiotic?
Nalidixic acid resistance is likely a result of the overuse of its family members. The sudden global rise in resistance has had a great impact on the interest from the academic community. Since 2000, resistance started to dominate the publications on nalidixic acid. In essence, nalidixic acid is a poster case for antibiotic resistance. In the past it was a popular drug, but now it mainly returns on resistance charts. Intriguing for scientists and a challenge for public health. If we learn from this pitfall, we may avoid others.

 

Academic publications on nalidixic acid. Blue: articles that mention resistance. Red: all others. Resistance becomes dominant after 2000. Source: https://www.ncbi.nlm.nih.gov/pubmed

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