Skip to 0 minutes and 7 secondsLet's talk about just another issue that is relevant to this issue of antimicrobial stewardship, and that's when we ask ourselves, are antibiotics a force for good or evil, we know that probably, the answer to that is both. They're essential, but they also can cause some issues. What's the goal when we're using antibacterial therapy? Well, we know that bacteria can cause illness ranging from minor to life-changing or life-threatening disease. We know that antibiotics can be absolutely lifesaving. But of course, not every bacterial infection needs antibiotic therapy. And what is important to recognise is that the goal of antibacterial therapy is to help the body eliminate infectious organisms without toxicity to the host.
Skip to 0 minutes and 53 secondsAnd this is, of course, much easier when we talk about antibiotics than when we talk about cancer drugs, which are actually targeting cancer cells but are very similar to the animal cells, whereas bacteria have a different structure, and therefore we can develop-- and have developed-- antibiotics that target bacteria but not the mammalian cell. So help is absolutely the key word, and we know that antibiotic therapy is most effective when it assists the natural defence mechanisms rather than acting as a sole means of infection control. What are these natural defence mechanisms? They're very important in preventing or controlling infection. Things like the mucociliary escalator in the respiratory tract, the flushing effect of urination, and gut normal flora.
Skip to 1 minute and 42 secondsAnd it's the gut normal flora and skin normal flora that we're going to be looking at at the moment. So bacterial resistance- we know that antibacterial agents do not actually cause bacteria to become resistant. Bacterial resistance didn't start with the discovery of penicillin. And when did that resistance start? Well, genetic analysis has shown that bacteria themselves invented antibiotics and antibiotic-resistant mechanisms developed quite some time ago-- i.e. like about 2 to 2.5 billion years. And basically, bacteria are in a sort of war with antibiotics and are constantly evolving ways of eluding their effects. So bacteria have been killing each other and using resistance mechanisms to protect themselves ever since.
Skip to 2 minutes and 29 secondsWhat we do know, however, is although antibiotic use doesn't actually create the resistance in the bacteria, it preferentially selects resistant populations of bacteria. The resistance will often emerge, not necessarily at the site of infection-- although that can occasionally occur-- but in the patient's normal flora, what we call the microbiome. And that is, essentially, the gut and the skin. This can result in acquisition of resistant infections or resistant bacteria, and that may be within the animal or be spread within the community. So the gut microbiome what does it do, and the skin microbiome? Well, we know that the microbiome has a really important role in physiological functions.
Skip to 3 minutes and 12 secondsIt plays a very important role in maturation of the immune system, and we know that the mammalian immune system development depends on instruction from resident commensal microorganisms. So it's very important, that interplay between the bacteria that are normally resident in the skin in the gut with the development of the immune system. And it's so important-- this sort of microbiome is-- that it's called the second brain because it has such an influence on so many things. The immune system has, of course, developed tools to cohabit with the microbiota, but also to keep it under control. And when there's a loss of control, this is called dysbiosis. Now, dysbiosis can occur in a number of ways.
Skip to 3 minutes and 56 secondsIf we look at these flora in the gut, so the normal would be homeostasis, and we have a nice range of different types of bacteria. The ones in red might be, potentially, pathogens, but they're being nicely controlled by the other population around them. And then, when we have dysbiosis, which is in the lower part of the diagram, we can have various ways this occurs-- either by expansion of pathogens-- so more red bacteria-- by reduced diversity-- which also results in expansion-- or by loss of beneficial microbes. Now, you might say, well, is this really relevant to me? You know, have I seen bacterial resistance in my practise? I might have seen it in some ears.
Skip to 4 minutes and 38 secondsHave I seen a urinary tract infection? Many vets will tell me that they really haven't seen resistant infections, so this issue about how I use antibiotics really isn't relevant to them. But actually, it is very relevant to them and relevant to all of us So let's just have a look at the bigger picture in relation to the microbiome. What we know-- and it's been very well established in people, and then a question mark in animals, but certainly a suggestion-- that disease is associated with abnormal immune responses towards environmental and self-antigens appear to have an increased prevalence-- diseases such as inflammatory bowel disease, multiple sclerosis, type I diabetes, allergies, and asthma.
Skip to 5 minutes and 23 secondsWe know that people with immune mediated diseases have a different microbial community compared with healthy individuals, and there's a lot of work that's been done that suggests that the pathogenesis, at least partly, of these immune-related diseases arises from improper training of the immune system by the microbiota. Antibiotics, we know, can have a significant impact on the microbiome, and we also know that many antibiotics can have long-lasting effects leading to permanent loss of some organisms. Other bacteria will outgrow and persist. And in general, we know that the structure of the microbial community can be influenced by many things-- genetics of the host, of course, diet, infection, but the one that's relevant to what we're discussing in this course is antibiotics.
Skip to 6 minutes and 13 secondsSo when we use antibiotics, we have to think about if we're using it appropriately or inappropriately. Actually, resistance is still going to emerge-- possibly at the site of infection if the treatment is inadequate or inappropriate, but always to some degree in the normal flora. There's a sort of perception that if I'm using an antibiotic for an appropriate reason, for an appropriate course, at an appropriate dose, then I'm not going to be contributing to drug resistance. And that may be true at the site of infection, but not in the normal flora. We know that the gut and the skin microbiome will be affected. What we do know, however, is that appropriate use has a benefit; inappropriate use does not.
Skip to 6 minutes and 59 secondsAnd this is why we always need to apply a cost-benefit analysis to when we use antibiotics. Do we really need to use them? Is this a disease that needs antibacterial treatment? Just because it's a bacterial disease doesn't necessarily mean it will need antibiotic treatment. Other times, of course, we know that it does.
Antibiotic use and the microbiome
In the video above, Jill Maddison, Professor of general practice at the Royal Veterinary College, discusses the importance of antimicrobial stewardship.
In step 1.3, the importance of AMS was discussed on an individual level, and in step 1.4 it was discussed on a more global level. This step looks at AMS on a microscopic level, within the context of the microbiome.
The goal of antibacterial therapy is to help the body eliminate infectious organisms without toxicity to the host. This is most effective when it assists the natural defence mechanisms rather than acting as the sole mechanism of defence.
The natural defence mechanisms in the body include the gut normal flora and the skin normal flora. This is the combination of resident bacteria that are always present, and it is called the microbiome.
The microbiome plays a huge role in development and maturation of the immune system. The body creates tools so that the immune system and the microbiome can co-habit, and the microbiome can be kept under control. If there is a loss of control of the microbiome due to reduced diversity, loss of beneficial microbes or an increased number of pathogenic bacteria, dysbiosis occurs.
Antibiotics can have a significant or long-lasting effect on the microbiome.
There is currently a belief that the appropriate and responsible use of antibiotics will not aid AMR, and while this may be true at the site of infection, resistance will always occur to some degree in the normal flora. For appropriate use, this can be justified, as the antibiotics bring other benefits, however inappropriate use of antibiotics brings no benefits.
The article in the see also section provides further reading on this topic, and the effect that antibiotics can have on your microbiome.
Please find a downloadable copy of the PowerPoint slides used in the video in the downloads section below.