Antibiotic of the week: Cephalexin

Antibiotic Pollution Index: 230 (19 November 2017)
What is the Antibiotic Pollution Index?

What it does
Cephalexin kills bacteria by disrupting molecules (peptidoglycan) in their outer layer. It is mainly effective against gram-positive bacteria, such as streptococci, staphylococci and bacilli. In these bacteria, this outer layer is unprotected, while in gram-negatives, this layer is thinner and protected by a membrane structure.

Who gets it
Cephalexin is widely used against ear, bone, joint, skin and urinary tract infections. It ranks around the 100th mostly used drug in the USA, with over 7.5 million prescriptions annually. It is also used in companion animals. In the USA, cephalexin is generally prohibited for food-producing animals, while in Europe, it is allowed: Maximum Residue Levels (MRLs) have been established up to between 100 micrograms and 1 mg/kg of cattle-derived meat and milk. This antibiotic is nevertheless not common in the European meat industry. For instance, in 2014, the class to which cephalexin belongs (1st and 2nd generation cephalosporins) made up 7 out of the total 9000 metric tonnes of antibiotics used in the 29 European countries. Globally, there is hardly any evidence for large-scale use of this drug in the food sector.

Where may it be produced?
Japan, USA, India, China, Israel, France, Brazil.

And, SquaredAnt, does it pollute?
Cephalexin has been detected in Australia, Vietnam and Saoudi Arabia, in concentrations between 0.1 – 0.3 ng/ml (rivers, aquaculture, WWT effluent) and 4 ng/ml (Hospital effluent). In large reservoirs such as rivers, those concentrations may be low, but do point towards a substantial spoilage of the drug into the environment and thereby indicate the presence of hotspots where resistance may occur. Indeed, a study from 2006 showed that over 40% of bacterial isolates from aquacultures in Australia carried resistance genes against cephalexin.

Warning lights
Cephalexin as an isolated case is a popular drug that does not ring alarm bells. However, cephalexin resistance is associated to two major forms of multi-resistance: extended spectrum beta-lactamase (ESBL) pathogens and methicillin-resistant Staphylococcus Aureus (MRSA). Companion animals are seen as potential sources for the so-called EBSL bacteria, especially E. coli and Salmonella strains. This may be related to the frequent use of cephalexin in companion animals: an estimated 40 percent of all dogs in the USA (roughly 35 million of them) receive at least one treatment of cephalexin each year. Because of its link to both MRSA and ESBL, cephalexin use and resistance may have to be observed in a broader context, where overuse of one antibiotic may accelerate resistance against the other.

Any common sense in this antibiotic?
Yes and no. The usage in food animals is restricted, but it is a poplar drug for pets, and patients. This may have played a role in some of the problems we face with resistance. For so far, the searchlights have not focused on cephalexin yet. As an example, ESBL is mainly seen as a consequence of more recently developed, broader spectrum family members of cephalexin. This may have lead to an underestimation of the role that cephalexin usage could play in this type of resistance. A more inclusive and systematic approach to antibiotic resistance may be needed.

Sources

  1. production locations
  2. general information
  3. general information
  4. Resistance genes in Australian aquaculture
  5. Maximum residue limits in Europe
  6. sales of antimicrobial drugs in 29 European countries in 2014
  7. cephalexin use in dogs
  8. companion animals as source for ESBL
  9. cross-resistance in MRSA
  10. number of pets in the USA

Antibiotic of the week: Spiramycin

Antibiotic Pollution Index: 37 (12 October 2017)
What is the Antibiotic Pollution Index?

What it does
Spiramycin belongs to a family that inhibits protein synthesis. Protein synthesis is an essential process. Proteins digest, transport, arrange and manipulate all sorts of cell components. In low dosages, spiramycin stops bacterial cell growth; in high dosages, it may kill the bacteria.
In the body, spiramycin is metabolized to neo-spiramycin, which is also an antibiotic agent. Ignoring this metabolic step may lead to an underestimation of antibiotic residue after spiramycin consumption.

Who gets it
Spiramycin is available in the EU and many other regions, but not in the USA. It is effective against a number of bacterial infections (such as Streptococcal, Legionella, Chlamydia, Mycoplasma) and is also used to treat toxoplasmosis, a parasitic infection. Veterinary use often targets respiratory infections. Spiramycin tends to bind to and accumulate in specific tissues, such as tonsils, bronchi, and (after injection) muscle around the injection site. This has advantages to target infections in those tissues, but its mixed accumulation in different organs challenges its use in the veterinary sector. Withdrawal periods -depending on the animal- up to 52 days have been recommended for this drug. Consumers may be exposed to spiramycin if withdrawal periods are not obeyed. For instance, micrograms per chicken egg can still be detected up to 10 days after treatment.

Where may it be produced?
France, China.

And, SquaredAnt, does it pollute?
For now, SquaredAnt only found one report of spiramycin in an environmental sample.

Warning lights
In France, resistance levels to spiramycin are high in some bacteria in pigs: up to 77% of Streptococcus suis is resistant against this drug. This particular pathogen has many resistance phenotypes. In Brazil, for instance, 99.61% of Strep. suis in healthy pigs is multi-drug resistant against at least 3 out of 16 antibiotics (spiramycin was not included in this analysis). This indicates that gradually, options to control Strep. suis infections are getting less. Strep. suis can infect humans, too. Alltogether, advancing resistance in this pathogen potentially has public health consequences.

Any common sense in this antibiotic?
The Antibiotic Pollution Index for this antibiotic is relatively low. This is likely the result of a limited usage of this drug on a global scale and its absence on the US market. The Strep. suis example shows us, however, that one day this drug may replace antibiotics that have been phased out due to antibiotic resistance. It will then be important to strictly control the use, as spiramycin resistance is related to its usage. Avoiding additional resistance phenotypes should be prioritized.

Sources

Antibiotic of the week: Amoxicillin

Antibiotic Pollution Index: 411 (12 October 2017)
What is the Antibiotic Pollution Index?

What it does
Amoxicillin works against gram-positive bacteria (bacteria with only one cell membrane). Few gram-negatives (which have two membranes) are also sensitive to it. This drug blocks the formation of the cell wall and kills the bacterial cell. It is often administered in combination with clavulanic acid, which, in essence, protects amoxicillin to be broken down by the bacteria it targets.

Who gets it
Amoxicillin is prescribed against throat, ear, lung, urinary or skin infections (often in children), and to treat Helicobacter pylori infections of the stomach. It is also used in farm and pet animals. In fact, amoxicillin is a commonly used “top critically important” antibiotic (as described in the UN List of Essential Medicines) in a number of pork farms in Europe. In Spain, one study found that 90 percent of pigs in so-called “finisher farms” was on antibiotics, where amoxicillin (51%) ranked only after colistin (61%) and doxycycline (62%) (please note that these 3 already sum up to more than 100%). Amoxicillin is used in some countries in aquaculture, too.

Where may it be produced?
Spain, Italy, India, China, Korea, Netherlands, Singapore, United Kingdom, Germany, Israel.

And, SquaredAnt, does it pollute?
Amoxicillin has been found in surface waters and waste-water effluents, generally in concentrations below 0.2 ng per ml. Sludge of from waste-water plants, on the contrary, may reach 79 ng/g. Such concentrations lie well above the predicted concentration of selection for resistant bacteria, which is estimated to be 0.25 ng/ml.

Warning lights
Health care systems fear a number of major resistance phenotypes, 3 of which (methicillin-resistant Staphylococcus aureus, vancomycin resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis) include amoxicillin resistance. Amoxicillin resistance in Helicobacter Pylori is also quite common in some regions worldwide, up to 50% in China.

Any common sense in this antibiotic?
Amoxicillin being pumped into pigs in the EU, as part of a cocktail of antibiotics, is indicative for quite a few shortcomings in pig breeding, health management, the meat industry and its underlying business model. Such overuse may be indicative for many regions in the world. In the USA, 19 out of 55 reported outbreaks of resistant food-borne pathogens were amoxicillin-resistant bacteria (mainly Salmonella). And, when a Jordan research group analyzed seafood imported from India, Egypt and Yemen, practically everything carried Salmonella and Shigella species that were antibiotic resistant… the majority of which against amoxicillin. Knowing that amoxicillin accumulates in sludge, it would make sense to approach the resistance in the context of fisheries and farms, and the link to human health via food, with more care.

Sources