Antibiotic growth promoters (AGP) for animal production are being increasingly restricted by the demands of regulatory agencies due to the growing bacterial resistance reported in different parts of the world, this also represents a loss of efficacy in their use as enhancers of animal performance.

Veterinarians committed to the intersectoral strategy “One Health” must assume our responsibility by ensuring the proper use of drugs, as this has consequences on human health.

In this sense, the prohibition or restricted use of colistin as a growth promoter and prophylactic is expanding throughout Latin America.

What is Colistin?

Colistin is an antibiotic that belongs to the polymyxin family, also known as polymyxin E. It is produced by the bacterium Paenibacillus polymyxa colistinus. Thanks to its surfactant properties, it can alter the permeability of the wall of sensitive gram-negative bacteria, which have an outer layer composed of lipopolysaccharides, and cause the death of these microorganisms.

Colistin is an antibiotic has existed for more than 50 years and was used in human and veterinary medicine. Its use in human medicine was discontinued due to its potential nephrotoxic and hepatotoxic effects, which is why it is currently used as a reserve antibiotic to treat conditions caused by multi-resistant bacteria.

Uses in veterinary and resistance development  

In veterinary practice, and, specifically, in poultry and pig production, the use of colistin has spread both for therapeutic purposes and to promote growth. As a therapeutic, it is an antibiotic of choice for the control of aerobic gram-negative bacteria, such as Enterobacteriaceae.

The use of colistin as a preventive or growth promoter, that is, in subtherapeutic doses, is the one that constitutes the greatest risk for the generation of resistance. The latest studies indicate that the generation of resistance is linked to the presence of transferable plasmids between species that contain genes that confer resistance to colistin (MCR-1 gene). This resistance generated by bacteria is also indicative of the loss of efficacy of the antibiotic to control enterobacteria and promote growth.

Current situation of colistin: limitations

The growing prohibition of this growth-promoting antibiotic and its salts in animals is due to its classification by the World Health Organization (WHO) as a “reserve” drug, due to its importance in public health as a tool that is effective in the treatment of infections caused by multidrug-resistant bacteria in humans.

In addition, as different surveillance studies reported cases of microorganisms that are resistant to colistin, it was decided to preserve its use for people.

Currently, the use of colistin as a growth promoter is already prohibited in several Latin American countries such as Argentina, Brazil, Peru, Bolivia, Paraguay, and Mexico; and it should not take long to reach the rest of the countries. In Central America, there are still no limitations.

Strategies to replacec colistin without losing efficiency

One of the keys to achieving good production rates in industrial animal production is the use of different tools to control the excessive growth of pathogenic bacteria in the digestive tract.

Today, there are different antibiotic growth promoters without limitations that could replace colistin; however, considering the global trend, they will probably be limited shortly. Bacterial resistance is not the only problem, but the residues that these drugs leave in meat, milk, eggs, and other animal products for human consumption. In this sense, consumers increasingly demand food that comes from animals that have not received antibiotics.

Nowadays, intestinal conditioner pronutrients and cimenol ring are the strategy that is more promising in countries that already apply these novel technologies in animal production.

Natural additives to replace colistin 

Research on additives based on plant extracts to replace AGPs is extensive; among which, due to their unique technology, the intestinal conditioner pronutrients and the cimenol ring stand out. These two compounds have advantages over the vast majority: they have a proven efficacy, are chemically defined, and are composed of active molecules with fully described molecular mechanisms of action.

Intestinal conditioner pronutrients

They are complex molecules of plant origin that improve intestinal physiology. Its mechanism of action, described by Biovet S.A, is based on the metagenetic stimulation of DNA genes with specific functions in enterocytes. They act as an external stimulus, increasing the synthesis of functional proteins by the enterocytes, which is reflected in a greater regeneration of the cells of the intestinal mucosa and an increase in nutrient absorption.

Intestinal conditioner pronutrients also improve the tight junctions between enterocytes, key to good intestinal integrity. These unions are composed of proteins (occludins, claudins), which are responsible for preventing pathogens from entering the body through the paracellular space and causing infections. An improvement in the anatomy of the villi and an increase in beneficial acidophilic flora has also been observed.

The use of pronutrients reduces disorders that affect the digestive tract and improves production rates: conversion rate, weight, mortality, meat quality, egg quality; additionally, they do not generate bacterial resistance, do not leave residues, and lack a withdrawal period.

Cimenol ring: natural antimicrobial

The cimenol ring is a substance of natural origin with antimicrobial capacity. It is present in different aromatic plants and acts as an intestinal biocide, controlling pathogenic bacteria (Clostridium, Salmonella and E. coli, among others) and, thus, favoring the development of beneficial bacteria. Its spectrum of action includes both gram-positive and gram-negative bacteria.

The effect of the cimenol ring can be enhanced by combining it with citric acid, since they act synergistically: citric acid generates pores in the bacterial membrane, facilitating the entry of the cimenol ring into the bacteria and causing destabilization of the plasma membrane and death by osmotic shock. The combined action of these two active compounds has been patented by Biovet S.A, which has studied this mechanism of action through its R&D department.

In addition, the cimenol ring also inhibits the synthesis of ergosterol, an important steroid in the membranes of fungi, enhancing its effectiveness against molds.

The cimenol ring can be combined with the intestinal conditioner pronutrients, since the first acts directly to control the microorganisms and the pronutrients prevent intestinal challenges by improving the integrity of the epithelium, thus, achieving a synergism between both natural solutions.

Conclusion

The increasing development of bacterial resistance is concerning, and alerts keeps the international organizations that monitor this extremely serious public health issue.

At the same time, the demand for safe, chemical-free food is growing. That is why the limitation of the use of colistin should reach all Latin American countries in the short term.

Having available natural technological additives that allow us to maintain or improve the production rates obtained with chemical additives, the smartest thing to do would be to expand the list of reserve antibiotics for human health by limiting more severely the use of growth-promoting antibiotics in animals.

The intestinal conditioner pronutrients and the cimenol ring have advantages over other additives since they have a proven efficacy and their composition is chemically defined, that is, they contain a specific number of active molecules with fully described mechanisms of action. Either in combined strategies or separately, they are effective in controlling Enterobacteriaceae and improving production parameters. Additionally, they do not generate bacterial resistance, lack of a withdrawal period, and do not leave residues in meat, milk, and eggs.

Intestinal conditioner pronutrients are marketed by BIOVET S.A. under the trade name Alquernat® Nebsui. They are available in premix and liquid and suitable for poultry and pigs.

The combination of cimenol ring with citric acid is marketed by BIOVET S.A. under the trade name Alquermold® Natural. It is available in premix and liquid and suitable for poultry and pigs.