Antimicrobials use and antimicrobial resistance in humans and food-producing animals

EFSA, EMA and ECDC have published a joint report on the correlation of the consumption of antimicrobials by food-producing animals and humans and the occurrence of antimicrobial resistance. Not surprisingly, they found positive associations between antimicrobial consumption and antimicrobial resistance in humans and food-producing animals but also, in some cases, positive associations between antimicrobial consumption by food-producing animals and resistance to antimicrobial agents exhibited by bacteria in humans.

'Mycobacterium tuberculosis bacteria'
by NIAID under a CC license

Antimicrobial resistance is a topic that I re-visit from time-to-time. In brief, antimicrobial resistance is the phenomenon where a bacterium acquires resistance towards an antimicrobial agent. This may happen via a spontaneous mutation or via gene transfer. The emergence of antimicrobial resistance is a very important issue, regardless of whether the micro-organisms where resistance is developed are, themselves, pathogens or not. Bacteria have the ability for horizontal gene transfer. Thus, once the genes responsible for a specific antimicrobial resistance appear in a microbial population, the propagation of the genes to other microbial populations, including different bacteria, will take place at some point. Obviously, this becomes critical when pathogens acquire such genes, especially when taking into consideration that the antimicrobial agents (antibiotics) we have at hand to fight them are finite (and rather few).

The report of the three agencies highlights a problem that has been known for a while but sometimes still tends to be overlooked. There are vastly different practices across countries with regards to the way that antimicrobial agents are used by doctors and veterinarians to tread human and animal diseases, respectively. To make things worse, residues of veterinary medicines in food-producing animals may also remain in the meat at the time of consumption. As you may suspect, bad practices in either of those fields can give further rise to antimicrobial resistance and, in the longer run, can both accelerate the emergence of antimicrobial resistance of human pathogens.

Given the increasing globalisation of livestock production, as well as the increased mobility of people around the globe, it is necessary to boost efforts for better management of the use of antimicrobial agents, both against human and animal diseases.

This is no simple task, though.

Optimum management requires resources and infrastructure that differ a lot from place to place. Think, for instance, that keeping food-producing animals healthy without resorting to the use of antimicrobial agents needs hygiene, animal-housing and health monitoring practices that come at a cost. On top of that, such animals may be less productive in terms of meat. Such effects discourage the adoption of practices featuring responsible use of antimicrobial agents. There, education, as well as legal measures, have a strong role.

In any case, however, the fact that the task in question is difficult that doesn't mean that the effort should halt. At least not until we find other, reasonably effective ways to deal with pathogens.

Antibiotic resistance and food (again)

'Mission San Juan Capistrano bells'
by Ballookey Klugeypop under a
CC license

Antibiotic resistance is the case where microorganisms become able to survive after exposure to antibiotics. Antibiotic resistance is not a new phenomenon. When resistance to multiple antibiotics is observed in pathogens then things become particularly alarming. Infections by multidrug resistant pathogens (superbugs) are very difficult - and sometimes impossible - to treat, especially when the patient's organism is weak.

I've written on superbugs before but recently antibiotic resistance re-surfaced in the news in a different way. As described by Maryn McKenna, seafood imported from South Korea to Canada was found with Pseudomonas bacteria, which turned out to carry a gene that enables the synthesis of a carbapenemase enzyme.  This is alarmingly important for a number of reasons:

• Carbapenamase enzymes can inactivate carbapenem, an antibiotic of last resort.
• Seafood is sometimes mildly processed, in some cases deliberately to retain flavour and texture, while in others it may simply be undercooked. In such cases, the bacterium found would be likely to survive.
• Non-resistant bacteria can acquire antibiotic resistance from resistant ones via horizontal gene transfer involving plasmids

If consumed, the bacteria in question could possibly make it to the gut. As they are not pathogens they would not pose a direct problem themselves but they would be likely to transfer antibiotic resistance to the gut flora bacteria. I am not aware of the probability of such chain of events but should it happen in individual consumers, it would create inside them a population of bacteria resistant to a class of last resort antibiotics. That's not a good thing to happen!

Carbapenem resistance in the food production system has been a concern previously. Unfortunately, this needs to be considered in tandem with the occurrence of carbapenem resistant infections that seems to be on the rise in Europe (but still under control).

The Canada seafood case highlights a different route of concern, where the consumers may be exposed to resistant non-pathogens (with the potential to be found on a variety of foodstuffs) rather than resistant pathogens, directly, or antibiotic residues in food, which could - in turn - potentially invoke antibiotic resistance.

There is a need for better monitoring of the various routes that can lead to antibiotic resistance. This is no small challenge, though (and it comes with a certain price tag)! However, without any need to panic, it is essential we understand what the risk is and adapt our food processing (and healthcare) practices accordingly. Such approaches work on the prevention front. Hopefully, we'll also make some more breakthroughs on the antimicrobial front, as well!

Superbugs

A few days ago, just before the entry of 2010, I came across an article on the BBC News website on the undesirable effect that disinfectants may have on bacteria. The article was supporting the the incorrect use of disinfectants (e.g., incorrect dilution) could allow bacteria to develop resistance to antibiotics.

I am by no means an expert in microbiology, or even plain-vanilla biology, however, I was aware that overuse or misuse of antibiotics could lead to increased resistance to those antibiotics; a trait which, once acquired by a group of bacteria, can be passed onto others, under certain conditions. In the hospital world, where people (patients) often have a weakened immune system, MRSA is a considerable threat, while an increasing number of other pathogens (or potential pathogens) begin to exhibit threatening tolerance to the available antibiotics, turning from simple "bugs" to "superbugs".

To my understanding, the antibiotics-induced antibiotic resistance can be mitigated by a tight antibiotic-use regime. Sweden has had considerable success in tackling the MRSA problem by forcing the health care system to resort to antibiotics only when absolutely necessary. The transition period might have taken considerable time but the gain sounds considerable: they can still make good use of antibiotics that on many place of this world are now considered to be ineffective.

The article of the BBC I spoke of earlier, however, is alarming in the sense that not only antibiotics but also disinfectants (and possibly other bacteria control means???) can somehow lead to antibiotic resistance. Clearly, improper use of disinfectants, which allows for a select portion of the microbial population to survive, favours that surviving population in the sense that it eliminates the competition. I would assume that this process effectively ensures that the descending bacteria will have those gene combinations that allowed their ancestors to survive the disinfectant. It seems, if my understanding of the article is correct, that those "disinfectant-survival" gene combinations can also be effective against antibiotics.

The alarming bit is that the use of disinfectants is much, much wider than the use of antibiotics. There not only used by hospitals but by a very high number of businesses, including the food industry, and they are also at hand in the typical household. I admit it would be inconsiderate to extrapolate that all disinfectants, if misused, could lead to superbugs. The fact that the number of known supebugs is still rather a small one, while the use of disinfectants has been more-or-less systematic over the last decades would rather support that the risk is minor.

I mentioned the food industry before. Interestingly, the agro-food industry was alarmed, in the past, by the antibiotic resistance problem but managed to sort it out by adopting good livestock practices and by considerably limiting the use of antibiotics. In Europe, there is legislation in place to ensure that things stay this way. But what about the use of disinfectants? The manufacturers of such products do include instructions for use, which normally are followed. I wonder though, with the modern foodstuffs enjoying increasingly longer shelf-lives, are there any significant chances that microorganisms which find their way into foods can turn into threatening superbugs?

In "live" foodstuffs (i.e., foods that contain a flora consisting of living microorganisms, such as yogurt, fermented sausages, various cheeses, tea, etc.), which contain a small eco-system, it is likely to be much easier to keep things under control. An undesirable contamination would be worse in the case of previously sterilised (or poorly sterilised) products under packaging conditions that lack bacteria growth barriers.

In any case, and for any of the existing reasons (ranging from health and safety concerns to competitiveness and sustainability issues), it may be worth revisiting some of the practices in our every day "war" with bacteria.

The use of good practices when it comes to cleaning surfaces or when actually using antibiotics has been proven to be an effective one. The use of phages to fight off antibiotic resistant bacteria has also been tested - successfully I believe; although, I'm not sure if it can find wide scale application beyond the health sector. The manipulation of the microbial ecology could be another promising sector, which has recently re-attracted research interest; after all, it may be time to remember that microorganisms are our valuable friends far more often than otherwise (not only when it comes to the function of the human body).

(Photo "big bug", CC by G J Hutton)