Prudent use of antimicrobial agents: not just for humans.

The use of antimicrobial agents (AA) is required for the treatment of infectious diseases, but, at the same time, is the main cause for the selection of antimicrobial resistant bacteria. The wide use of AA in human medicine is a key cause of this problem, but not the only one, as other ‘‘non-human’’ uses of AA are also contributing to the alarming increase of resistant bacteria. AA are used in animals for therapeutic and prophylactic purposes in order to cure and prevent bacterial diseases. In these cases, AA are administered under veterinary control. Another use of AA in animals, although banned since 2006 in the European Union (EU) but still allowed in other non-European countries (USA, Japan, Australia, among others), is as animal growth promoters (AGP). In this case, AA are added in sub-therapeutic doses and for long periods of time in the feed of healthy animals, conditions that could contribute to the selection of resistant bacteria. The use of AA as AGP has been the object of strong debate in the scientific community for its potential risk to human health. AA use as AGP is associated to the selection of resistant intestinal bacteria in animals (both zoonotics and commensals), that could be transferred to humans through the food chain; these selected bacteria could also transfer resistant genes to other human intestinal bacteria. There are different regulations for AGP use in those countries where they are still allowed. The use of avoparcin as AGP in the EU, a glycopeptide with a similar structure to vancomycin, is a clear example of the contribution of this use in the selection and dissemination of vancomycinresistant enterococci in the animal ecosystem, with its potential risk to human health. After the EU banning of avoparcin as AGP in 1997, the prevalence of these resistant bacteria in intestinal samples of animals and healthy humans and in foods has significantly decreased. The use of AA to treat or to prevent infectious diseases in food producing animals (FPA) also contribute to the selection of resistant bacteria that can be transferred from animals to humans. The food chain is considered as a transmission vehicle of resistant bacteria to humans, although direct animal-human contact can be another transmission route. Some examples will be highlighted. The introduction of fluoroquinolones (FQ) in animal production was associated with an increase of FQ-resistant bacteria isolated from FPA (as Campylobacter or E. coli, among others) and, later, in zoonotic bacteria implicated in human infections. However, in Australia, where FQ are not used in FPA, this association has not been observed. FQ use in poultry was banned in Denmark in 2003, and was followed by a decrease in the percentage of FQ-resistant Campylobacter coli isolates of chicken origin. Similarly, the US Food and Drug Administration (FDA) banned the use of enrofloxacin in poultry in 2005 due to its possible risk to human health. Another major cause of concern is the emergence and dissemination of extended-spectrum beta-lactamases (ESBL) among clinical E. coli isolates, especially those of the CTX-M group. Different studies have shown that the intestinal microbiota of FPA is a reservoir of ESBL-containing E. coli isolates. These resistant bacteria have also been recovered in pets, wild animals and in food samples. Although the factors involved in this phenomenon are complex, the potential animal to human transference through the food chain cannot be ruled out. The low use of cephalosporins in animals (compared to humans) suggests that co-selection with other AA widely used in animals, such as sulphonamides or tetracycline, may be involved. As a matter of fact, most of the strains carrying ESBLs harbour tetracycline resistance genes or integron structures that contain sulphonamide resistance genes. The use of broad-spectrum cephalosporins in animals should continue to be restricted and carefully controlled due to the importance of ESBL-related resistance for human-health. It is also of great interest to mention the dissemination of a specific genetic variant of methicillin-resistant Staphylococcus aureus (MRSA), ST398, associated with the animal environment, particularly pigs, and that can be transferred to humans, mainly where there is close contact with colonized animals. MRSA ST398 strains are often resistant to tetracycline. There is debate on the possible relationship between the high use of tetracycline in animals (especially in pigs) and the emergence of ST398 in animals. The use of AA in companion animals or pets is also contributing to the resistance problem, both in pathogenic and in commensal bacteria, as these animals are considered as a reservoir for resistance bacteria. Curiously, the use of AA in www.elsevier.es/eimc