Worms and Germs Blog : Animal Health & Diseases : University of Guelph : Ontario Veterinary College : Zoonotic Diseases : Guelph, Hamilton, Ontario

Antibiotic resistant bacteria are a huge problem in human medicine, and they're an increasing problem in veterinary medicine. In pets, we are seeing dramatic increases in multidrug-resistant bacteria, some as a result of transmission from humans and some that are developing in animals. Regardless of the source, infections caused by resistant bacteria are a major problem. As resistance increases and we have fewer and fewer treatment options for some infections, the potential need to use certain antibiotics that are important for serious infections in humans ("big-gun" antibiotics) increases. This is a very contentious issue because concerns have been raised over the use of these drugs in animals and the potential impact on humans.

There are two extremes to the argument:

1. These are critically important drugs in human medicine and they should never be used in animals.
2. These drugs are used thousands of times a day in people and very rarely in animals, so the impact of periodic use in animals should be minimal, and failure to use them would result in animal deaths from potentially treatable infections.

I take the middle ground here. I am very concerned about antibiotic resistance (in pets and people) and I want to make sure that what I do does not have a negative impact on public health. I also realize that very rare and appropriate use of these drugs will realistically be unlikely to have any negative impact on public health, and that withholding treatment could cause animal suffering, death and prolonged infections that could be transmitted to their owners. The key, to me, is ensuring that use of these drugs is truly very rare and appropriate. At the Ontario Veterinary College, we have strict guidelines for use of "big-gun" antibiotics to try to ensure that there are used rarely and properly. For example, vancomycin can be used, but only when:

• An infection is present and it is known that the bacterium is resistant to all other options and susceptible to vancomycin.
• Local antibiotic administration or other types of alternative treatment are not options.
• It's a serious infection that needs to be treated but it is treatable (i.e. no throwing a big gun drug at a patient that clearly has a terminal disease and does not have a realistic chance of surviving).
• Approval is obtained from the Chief of Infection Control (i.e. me).

With this approach, we've only had 1 case where vancomycin was used, and that was in 2001. That's a pretty good record for a busy referral centre with a tertiary care caseload that sees "the worst of the worst." There have been a few instances when vancomycin was requested but with discussion and review of the case, better alternatives were identified. I'm certain that these guidelines have reduced the use of vancomycin and increased awareness of the problem, but have had no negative impact on patient care.

Antimicrobial resistance isn't going away. We can control it but not eradicate it. Scrutiny of antibiotic use in veterinary medicine is also not going to go away, and in some ways, that's a good thing. It should provide impetus to make sure that we improve how we use drugs, from the big guns down to our day-to-day drugs. Realistically, it's the regular use (appropriate use, overuse and misuse) of less exotic antibiotics that is having a bigger impact on antimicrobial resistance, and we need to pay attention to that as much as to the high-profile drugs.

(Click image for source)

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A recent study just published in the journal Emerging Infectious Diseases evaluated risk factors for dogs having an infection with methicillin-resistant Staphylococcus aureus (MRSA) versus methicillin-susceptible S. aureus (MSSA). This study, headed by Dr. Meredith Faires, compared dogs with MRSA versus MSSA infections from three different veterinary referral hospitals in Canada and the US. Among the more important findings were the following:

• Staying in a veterinary hospital was not a risk factor for MRSA infection, reinforcing the notion that this is predominantly a community-associated disease in dogs (meaning it typically develops in dogs in the general population).
• Most infections, in both the MRSA and MSSA groups, were skin infections. While serious deeper infections can and do occur, skin and ear infections are very common.
• Prior treatment with antibiotics was associated with development of MRSA versus MSSA infections. Dogs that received any antibiotic within 90 days were approximately 3.8 times as likely to have MRSA versus MSSA infection. Dogs treated with drugs from the fluoroquinolone class of antibiotics were 4.6 times as likely to have MRSA versus MSSA infection.

The association between prior antibiotic use and development of a resistant (i.e. MRSA) infection is not surprising, but it is important to document these events and to be aware of them. Antibiotics are critically important drugs in veterinary and human medicine. They save countless lives, but are also overused and misused frequently, and resistance is a critical problem. Studies such as this demonstrate the need for prudent antibiotic use - use them when needed, but use them properly.  Don't use them when a bacterial infection is not present or unlikely to occur.

The study can be downloaded by clicking here. More information about MRSA in available on the Worms & Germs Resources page.

Image source: http://animalphotos.info/a/

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Clostridium difficile is a high-profile bacterium, being an important cause of illness and death in people. It can also be found in various animal species, including dogs and cats. In a study we published earlier this year (Lefebvre et al, Journal of the American Veterinary Medical Association, 2009), factors associated with acquisition of Clostridium difficile by dogs involved in hospital and non-hospital therapy programs were assessed. Things that were significantly associated with a dog acquiring C. difficile were:

- Contact with human hospitals: Not too surprising since it's clear that hospitals can be highly contaminated with C. difficile and the hands of some patients petting the dogs are probably also contaminated.

- Contact with children: Most parents know that kids are biohazardous (we've getting over a round of illness in our house brought home by the kids - not an unusual event). Whether the increased risk for dogs is because kids have higher rates of C. difficile carriage, or because they have closer contact with dogs (with little hygiene) or some other factor isn't clear.

- Recent use of antibiotics: No surprise here. Antibiotic use is a well-recognized risk factor for C. difficile, since antibiotics can disrupt the normal protective bacterial population of the intestinal tract and allow C. difficile to grow.

- Recent use of antibiotics by a person in the house: I think this is a fascinating result and a great example of the close inter-relatedness of people and pets microbiologically. What presumably happens is that when someone is treated with antibiotics, they are more likely to acquire C. difficile and pass it in their feces. By doing so, there is a greater chance that their dog will be exposed to C. difficile, perhaps from the person's hands or the household environment. (The toilet would be a great source if the dog's a toilet-drinker). The implications of this, for both dogs and people, are unclear. It could be primarily an academic risk (i.e. of little practical significance), or it could be that interspecies transmission of C. difficile plays a role in disease in both species. We simply don't know at this point.

This is also a good example of why educational efforts regarding prudent antibiotic use need to be directed at both animal and human healthcare.

More information about Clostridium difficile can be found on the Worms & Germs Resources page.

Image source: www.sciencedaily.com/releases/2009/05/090507101820.htm

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Methicillin-resistant Staphylococcus aureus (MRSA) infections are an emerging problem in dogs and cats. They're a huge problem in human medicine, and the emergence of MRSA in pets can be directly traced to the spread of MRSA in people.

A big problem with MRSA infections is that they can be difficult to treat because they can be resistant to many antibiotics (not just methicillin). This complicates treatment, but it's important to remember that most MRSA infections are treatable.

An important concern with MRSA is that it may lead to unnecessary veterinary use of drugs that are critically important for treatment of life-threatening infection in humans. Vancomycin is an antibiotic that is occasionally used to treat MRSA infections in dogs, although I've never had to use it. I stumbled across a supposed "veterinary information website" today that stated vancomycin is the main treatment for MRSA in dogs. It quickly became clear the authors had no clue about the topic, because they kept calling MRSA a virus (always scrutinize the source of information, especially on the internet). Information like this doesn't help with prudent use of drugs like vancomycin.  It's important for pet owners and veterinarians alike to realize that these "big-gun" antibiotics (such as vancomycin) are rarely needed for MRSA infections in dogs and cats. There are almost always other, and usually better, options.

Vancomycin is also sometimes inappropriately used in animals, which can lead to worsening of infection.  For example, if vancomycin is mistakenly given orally, the drug is not absorbed from the intestinal tract and therefore has no chance of fighting infection elsewhere on the body.

In general, MRSA infections are quite treatable. Survival rates tend to be high and, with proper treatment, should be no lower for MRSA infections versus infections caused by susceptible strains of S. aureus. A comparison of MRSA versus susceptible S. aureus infections presented last year reported no difference in survival rates, with an overall survival rate of >80%. The key is diagnosing the infection early and getting started on the right treatment. That means getting cultures done earlier, rather than later.

While increasing antibiotic resistance may lead to more need for "big-gun" antibiotics in some cases, we need to act prudently and restrict their use to situations in which they are absolutely required. Use in animals needs to be very prudent to avoid contributing to antibiotic resistance in people. Inappropriate use in animals could lead to more calls to restrict veterinary access to various drugs, which could threaten treatment of other animals with other types of infections.

Don't confuse "big-gun" antibiotics with the best treatment.

More information about MRSA can be found on the Worms & Germs Resources page.

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People are justifiably concerned about overuse of antibiotics, in both veterinary and human medicine. There's ample talk about restrictions on use of antibiotics in animals (especially livestock), which is an area that needs good, objective research and discussion. Some politicians have made grand statements about restricting antibiotic use and have proposed strict legislation. (In North America, there's a lot more talk than action). However, I continue to be amazed that amongst all the hand-wringing about antibiotic use in animals, governments haven't taken the very simple initial step of making all antibiotics only available by a veterinarian's prescription. This seems to be a very logical first step, but it's one that almost never gets discussed.

A good example of why this type of regulation is needed comes from a website about Terriers, which says:

"Almost all human antibiotics can be used on dogs and almost everyone either has old antibiotics in their medicine cabinet or knows people that do. Look around, and you will probably find what you need."

• What??!! Just what we need... recommendations that people sift through old drug supplies for a dose or two of who-knows-what, which may or may not be expired and may or may not be potentially useful for whatever problem is present, and may even be harmful. Determining whether or not an antibiotic should be used, and determining the drug and dose is not something that should be up to a pet owner. It should be up to a veterinarian.

"Drugs past the expiration date are going to be fine as long as they are no older than a year or so past the expiration date (even then they may be fine)."

• Dumb. Drugs don't instantly go bad at their expiration date, but you don't know what you have left at that point. If you actually need an antibiotic, you need one that works like it's supposed to.

"If you prefer to order your medications outright, you can order cephelaxin (Fish-Flex) from most dog catalogues and it will cure 99% of your flesh wounds as well as most urinary tract and ear infections. Cephalexin or cefalexin is sold as a fish antibiotic in dog catalogues with full-knowledge it is being used for off-label treatment in dogs. It should cost about $30 for 100 250 mg. capsules, which is a perfect dose for a terrier."

• Ugh!!  A good example of why loopholes like easy access to antibiotics for fish use need to be closed. Many dog internet sites sell fish drugs. I wonder what percentage of "fish" drugs actually make it into fish?

"You probably have some old amoxicillin around the house from the last time you got sick. This is fine to use even if "expired" more than a year ago. Expiration dates on non-liquid antibiotics are a marketing tool (i.e. they encourage people to throw good drugs down the drain) and have no scientific basis -- a fact demonstrated by the U.S. military."

• Can't say I've seen that study. Expiry dates aren't a marketing ploy. You should use all the antibiotics prescribed, and if for some reason you have any left, you should throw the rest out. It has to do with health and proper use of antibiotics, not marketing.

Take home messages:

• It's time for politicians to actually do something about antibiotic use and ban all over-the-counter access.
• Beware of internet advice. Scrutinize sources of information carefully.

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In an interview with the San Francisco Chronicle, veterinary dermatologist Dr. George Doering makes a pretty obvious but very important comment that is worth repeating:

"The biggest problem we have in almost all the fields of veterinary medicine is compliance. You say to a client, "This dog needs to take this antibiotic twice a day." Well, the reality is we might be lucky if they get it once a day. ...They don't want to accept the seriousness of the problem."

This very true and very important. Compliance with recommended antibiotic therapy is probably a major factor in treatment failure, recurrent infection and antibiotic resistance. Antibiotic dosing regimens are specifically designed to ensure that the right concentration of drug is present in the body for the appropriate time. Missing doses, skipping days, not making sure the animal actually ingests the drug, and other problems that result in the pet not getting what is was supposed to get are very important.

It's easy to understand why this happens, because administering antibiotics (particularly to some difficult-to-pill dogs and cats who can smell the medication when it comes in the house!) can be a hassle. Because of this (and the very natural human tendency to take the easy way out), it's really important for people to understand the concerns about inadequate antibiotic administration and what they need to do.

• Follow the entire treatment course. You should have no antibiotic left at the end of the recommended treatment time.
• Make sure your pet actually swallows the antibiotic. If you add pills to food, make sure you check to see that the pill isn't left behind. It's amazing how animals can eat a big bowl of food and leave behind a little pill. The picture shows how my dog Meg can, in the process of inhaling her food at an incredible rate, leave behind a tiny ephedrine pill.
• If your pet will not eat the drug voluntarily, talk to your vet about other ways to administer it, such as compounded in chewable treats. Depending on you and your pet, opening your pet's mouth and placing the pill at the back of the tongue may be an option. Talk to your vet about this first and make sure you wash your hands after. If you think there is a risk you might be bitten, if you are at high-risk for infection because you are immunocompromised, elderly or pregnant, don't try to "pill" an animal in this manner.
• If you still can't get the drug into your pet, talk to your vet right away.  If you wait a couple of days or a week or more to tell your vet, your pet may be even sicker by then. There may be other options to oral drugs such as injectable antibiotics. This might end up being more expensive or difficult (e.g. you may have to take your pet to the vet every day for its medication), but it will be better for your pet and may even save you money in the long run by ensuring the infection is properly and completely treated the first time.
• Never stop treatment because your pet looks better. Often, signs of infection get better before the bacterium is completely eliminated. Stopping too soon allows the bacterium to regrow, potentially as a more resistant form.
• If you are supposed to take your pet to the vet for a recheck at the end of treatment, then do so. Sometimes longer courses of antibiotics may be needed, and it's much better to continue the current treatment course than to have to start again a couple weeks down the road when the infection has returned (sometimes with a vengeance).
• If in doubt about anything, call your veterinarian.  He or she is there to help, and wants your pet to get the best treatment possible.

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As we see more and more infections caused by antibiotic-resistant bacteria, we have to re-think our approach towards antibiotic therapy. This often involves using new drugs, but sometimes it also involves considering the use of older drugs that we haven't used very much for a long time.

One such drug is chloramphenicol. Years ago, this antibiotic was widely used, and is still used in people and animals in some situations. In some respects, it is a very good antibiotic - it is often effect against many bacteria including those that are resistant to many other drugs, such as MRSA and MRSI/MRSP.  Chloramphenicol can also be given orally, and it's relatively cheap. Unfortunately this drug can also be very toxic, both to the animals being treated with it and to people that come in contact with with it in the process. In some animals, chloramphenicol can cause suppression of the bone marrow, where red and white blood cells are produced. This is more of a concern with long term use, but if the bone marrow does become suppressed, stopping treatment with the chloramphenicol typically resolves the problem.  Unfortunately, this bone marrow suppression is much more of a concern in people - the supression is very severe, and can occur with exposure to even a very low dose (or probably single dose) of chloramphenicol.  This results in a condition known as aplastic anemia,  which it typically fatal.  Fortunately this reaction is very rare in people, but there is no way to predict who might develop this condition, and since it is usually fatal, we obviously need to be cautious about using this drug. In some countries, chloramphenicol use in banned in all animals. In many others, it cannot be used in food animals, but can be used in pets.

• Chloramphenicol should only be used as a drug of last resort. There are situations where it is useful and may be life-saving, but the human health risks cannot be overlooked.
• If chloramphenicol is being considered, it is critical that  people who would need to handle the drug understand the risk and how to safely handle the drug to avoid exposure.
• Chloramphenicol tablets should not be crushed or otherwise processed at home because of the potential for breathing in the drug when it is in powder form.

Direct contact with pills or liquids should be avoided by use of gloves or other safe handling practices.

• If a liquid form is used and is squirted onto food, the food bowl should be handled as if it is contaminated.
• If pills are being used, the animal should be observed to ensure that the pill is ingested and not spit up and left on the floor.
• Contact with the mouth and face and animals that are being treated with chloramphenicol should be avoided in case drug residues are present.

If people are unable or unwilling to follow safe handling recommendations, they should not use this drug.

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A common question from owners of pets infected with methicillin-resistant Staphylococcus aureus (MRSA) is "Where did it come from?" The answer is not completely clear, but evidence strongly suggests it probably came from humans. The MRSA strains found in pets are almost always teh same as those found in people (including people that don't have pets) in the same geographic area. This strongly suggests that the MRSA came from the same source. Considering the fact that S. aureus in general is much more common in humans than in pets, and how long MRSA has been around in people, and that MRSA can sometimes be found in both people and pets in the same household, it is very likely that MRSA can move between species and originally went from humans to animal.

Even though MRSA in pets probably originated from people, now that it is in the pet population, pets can spread it to other animals and back to people. It is unclear how frequently this occurs - most people are still more likely to encounter MRSA from another person than from an animal.

The emergence and spread of MRSA in humans was largely driven by extensive antibiotic use in people.  Once MRSA crossed over to pets, antibiotic use in these animals almost certainly played a role in helping MRSA spread in the pet population. Antibiotic treatment has been identified as a risk factor for development of MRSA infection in dogs, and for MRSA carriage in horses.

Prudent antibiotic use is likely the most important factor in reducing the risk of MRSA in individual pets.  Using antibiotics prudently means doing things like:

• Only using antibiotics when they're really necessary
• Using the most basic antibiotic possible (instead of the fanciest or most powerful antibiotic)
• Finishing every prescription completely and as directed)

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