VetInfo Digest May 2000
This Month:
Online Veterinarians -- A Controversy
Antibiotics -- Why don't they always work?
New medications and new uses for older medications
Sheba
In researching information for an upcoming continuing education seminar that I will be presenting, I came across a human medical web site promoting a concept called "evidence based medicine". Suddenly, I realized that there was a name for the concept we have been trying to promote on www.vetinfo.com and through the VetInfo Digest. Much of medicine is based on "what I was taught"; "what my experiences have been" and "who do I trust". I believe it should be based on "can you prove you are right with objective studies ?". This concept is now called evidence based medicine in the human medical literature. It is a good concept, in my opinion, because it doesn't categorize medicine into "alternative" or "conventional" or "complementary" - it categorizes medicine into "can you prove it works", or not? If this concept catches on, it should ease the tension between practitioners of all sorts of medicine because it doesn't matter if you know or can theorize why a treatment should work --- it only matters that you can prove it does in objective studies. The majority of veterinary practitioners should be able to accept that concept. Ask for the evidence!
Online Veterinary Advice Stirring Up Controversy Among Vets
This month there have been a number of articles about on-line veterinary advice in the veterinary magazines. Soon there will be a number of new services for pet owners seeking veterinary advice on the internet. There will be a service affiliated with the Angell Memorial Animal Hospital in Boston that will reportedly offer real time veterinary advice, using the services of five veterinarians hired specifically for this purpose. It will be part of petplace.com, the service which has also replaced the Pet Care Forum on America Online. Dr. Johnny Hoskins, formerly a professor at Louisiana State University's veterinary school is also offering online advice on a case by case basis, for a fee. Dr. Hoskins was quoted in DVM Magazine as saying that he would couch his answers in technical terms, making it necessary for pet owners to consult with their veterinarians. Another veterinarian was quoted as saying that providing online advice was practicing medicine without a doctor patient relationship. Perhaps the most scary part of the articles was advice from a veterinarian who is also an attorney, who simply stated that she would strongly recommend that all veterinarians refrain from giving advice to anyone not living in the state in which they are licensed to practice.
So what does all this mean for our web site and newsletter? The reason that we insist that all questions be submitted in writing and answer them all in a written format is simple. We try very hard not to cross the line that separates explaining medical problems and actually practicing veterinary medicine via the internet. This will continue to be our policy. We will continue to try to provide information in language you can understand. We encourage you to take advantage of other web services when it seems necessary. We want you to understand that you really do need a vet you can talk to in person and who can examine your dog or cat and provide you with their experience in caring for pets. Do not underestimate the value of this relationship to the health and well-being of your pet. Your vet's opinion is more valuable than ours, most of the time. But on the days your vet is too busy to explain a disease or to discuss treatment options, we also want you to have a source of information on pet health care that is validated by evidence, whenever possible.
Michal and I have decided that the only way to meet our goals, for the time being, is to stay independent and to depend primarily on subscriptions for support. This will allow us to provide information that is as unbiased as we can make it. We have seven hundred subscribers at the present time. As always, we thank you for your support and we hope that you are pleased that you are the helping us to provide information on pet health care for people all over the world.
Antibiotics: What are They and Why Don't They Always Work?
There has been some interest in the last couple of months in how antibiotics work and why one antibiotic might be better than another in certain circumstances. In addition, there is some frustration over the fact that antibiotics don't always seem to work even when great care is taken to select the proper antibiotic through culture and sensitivity testing. Antibiotics are real miracle drugs, but they do not work in all circumstances or for all disorders.
The word bacteria is actually the plural form of the word bacterium. So there isn't such a thing as a single bacteria --- but you can have one bacterium! Bacteria are prokaryotes, which are single cell organisms that lack a nucleus and nuclear membrane. They share this classification with blue-green algae. Bacteria come in many species and several general classes. Aerobic bacteria require oxygen to survive. Anaerobic bacteria can gather energy from fermentation, making it possible for them to thrive in necrotic (dead) or damaged tissues. Facultative bacteria can adapt to the environment and use aerobic or anaerobic processes to gather energy. These bacteria are common in the intestinal tract where this trait is useful for survival.
Another way to classify bacteria is by use of Gram's stain. This staining process causes some bacteria to stain deep purple (gram-positive) and other bacteria to stain light red (gram-negative). The difference in staining occurs due to differences in the chemical composition of the cell wall in different types of bacteria. This difference is clinically significant because it also affects which antibiotics will work. There are some antibiotics that are much more effective for gram-positive bacteria than for gram-negative bacteria. A bacterium can be gram-negative and anaerobic, gram-negative and facultative or gram-negative and aerobic. The same three possibilities exist for gram-positive bacteria. Using both classification schemes can make the choice of an antibiotic easier.
Where bacteria chose to live also has an impact on the type of antibiotic used. There are several barriers in the body which protect certain organs or tissues. A blood/brain barrier prevents many substances from entering the brain from the blood stream. If there is a bacterial infection of the brain, using an antibiotic that can not cross the blood/brain barrier easily may result in an ineffective use of the antibiotic, even though bacterial culture and sensitivity testing and bacterial classification suggests that the antibiotic should be effective. Bacteria that live in abscesses or in severely damaged tissue are much harder for the body to kill. It is necessary for the antibiotic to be able to get into the abscess or damaged tissue in sufficient quantities to be able to kill bacteria, often without much help from the immune system. In some other cases, bacteria have learned to live inside of the white blood cells that normally remove them from the circulation or inside of other cells in the body. While the bacteria is inside the cell, it may not be susceptible to the effects of antibiotics, making it very difficult to eliminate the resulting infection.
Sometimes, the body's reaction to a disease or an infection enhances the survival of the bacteria, instead of helping. This can occur in situations in which inflammation restricts blood flow and leads to areas of dying tissue in the body. Intestinal ileus, or stoppage of the normal contractions, can lead to gas pressure, pain and inflammatory responses that actually make it easier for bacteria to invade the intestinal tract. Urinary bladder infections sometimes seem to be benefited by an inability of the body to mount an effective immune response to an infection that is actually "outside" the body. This is easier to envision if you think of the urinary bladder as being a really deep fold in the tissue with a very narrow entrance, which is exactly what it is. Bacteria may thrive in an environment that is really hard for the white blood cell system to survive in. Without the help of the immune system, an antibiotic may not be effective, even if it does have the ability to kill or suppress the bacteria involved in an infection. A dog or cat that is ill may not feel well enough to eat properly. Over time, this may lead to a decreased ability to produce antibodies and other proteins necessary to fight off bacteria.
Pain can interfere with healing. Animals that are in pain are diverting some of the energy they could be using to fight off bacteria to pain control. In addition, their bodies are producing inflammatory responses and releasing powerful hormones that can decrease blood flow to many areas of the body. Adequate pain control can be the difference between an antibiotic working and not working.
Sometimes bacteria can even help each other survive. A aerobic bacteria that produces an abscess may make it possible for an anaerobic bacteria to thrive. Bacteria that cause severe inflammation may also improve the conditions for other bacteria. Sometimes the secondary bacteria is the only one that will grow on a culture sample, making it possible to choose an antibiotic that won't succeed in entirely eliminating an infection, even if it does kill the bacteria that grew on the culture plate.
Antibiotics themselves come in a variety of forms. One of the major methods of classifying antibiotics is bactericidal versus bacteriostatic. Some antibiotics are capable of killing bacteria outright. They do not actually need the assistance of the immune system to completely eliminate bacteria, if they can be delivered to the infection site in adequate quantities and if the bacteria involved in the infection are susceptible to them. Bacteriostatic antibiotics are capable of interfering with the reproduction of bacteria or inhibiting them in some other way that prevents growth of the bacteria population but are not able to kill the bacteria without the help of the immune system or some other outside source.
Antibiotics are often divided up based on their underlying chemical structure, as well. Penicillins include penicillin-G, amoxicillin , ampicillin and similar medications. Fluoroquinolones include enrofloxacin (Baytril Rx), orbifloxacin (Orbax Rx), marbofloxacin (Zeniquin Rx), others. Cephalosporins such as cefadroxil (Cefa-Tabs Rx) and cephalexin (Keflex Rx) make up another class of antibiotics. Tetracyclines include oxytetracycline, chlortetracycline, minocycline and doxycycline. Macrolid antibiotics include erythromycin and lincomycin (Lincocin Rx). Aminoglycosides are gentamicin (Gentocin Rx), amikacin (Amiglyde Rx), neomycin and kanamycin. Some antibiotics are "potentiated" by the addition of more an ingredient that makes it harder for bacteria to resist them. Two examples of this are amoxicillin-clavulonic acid (Clavamox Rx) and sulfa-trimethoprim combinations (Tribrissen Rx, Ditrim Rx, Primor Rx, smz-tmp generics). There are other antibiotics classes but it is most important just to realize that there are different classes of antibiotics and that their physical properties make them better suited for some infections than for others.
In order to choose an appropriate antibiotic, your veterinarian has to consider a number of variables. The antibiotic should work for the type of bacteria that is causing the problem and it must be able to penetrate the affected tissue well enough to obtain therapeutic concentrations. It shouldn't be toxic to the patient. If possible it should be dosed only once or twice a day to make it possible for most clients to administer it. Cost may be a factor. When possible, most vets favor inexpensive antibiotics in selecting an initial antibiotic, if all other factors are equal.
There are general guidelines for antibiotic selection that make it possible for your vet to choose an antibiotic initially without the benefit of a culture and sensitivity test. In skin, for instance, the cephalosporins, potentiated sulfas and macrolid antibiotics are usually effective. This makes it reasonable to choose them as a first choice antibiotic before bacterial cultures are done. Other body systems require different first choice antibiotics. Often, your vet will choose the first antibiotic therapy based on lists of antibiotics that should work for most infections in a particular site.
It is important to realize that some antibiotics have different dosing requirements depending on the site of infection. This is important enough that some of the producers of newer antibiotics have successfully petitioned the FDA to allow practitioners to use their judgment for dosing, by allowing "professional flexible dosing" guidelines. It is entirely possible for a veterinary client to have two pets that weigh exactly the same, on the same medication for two different conditions and to have two different dosages that are both correct. This has actually happened in our practice and the owner called to inquire how that could be, because I failed to explain the difference in dosing adequately during the exam.
It is critical that you administer antibiotics according to the directions on the label. If you have any questions about the directions or if you are unable to administer the medication you should call your vet as soon as possible. Most vets understand that some patients are hard to give medications to and will work with you to find a dosage form that will work. Some antibiotics can be compounded at special pharmacies to make them into palatable liquids or gels, which can be especially useful in cats. In addition, for medications with a bad flavor it is usually acceptable to purchase capsules from the pharmacy and put small pills into the capsules, if they fit. Following your veterinarian's dosing recommendations helps to avoid relapses from inadequate treatment periods, bacterial resistance in the future and even transfer of bacterial resistance to microbes that infect humans.
Many antibiotics cause diarrhea or vomiting in at least some patients. It is usually acceptable to treat the diarrhea with loperamide (Immodium AD, tm) or diphenoxylate/atropine (Lomotil Rx), but you should check with your vet about this, especially if a digestive disorder is being treated. Usually the diarrhea will last about the same amount of time if the antibiotic is withdrawn or continued, but withdrawal of the offending antibiotic is acceptable if it is replaced with another appropriate antibiotic. Vomiting induced by antibiotics usually makes it necessary to use another antibiotic.
There can be severe reactions to antibiotics in some animals. The aminoglycosides, such as gentamicin can cause kidney failure or inner ear damage. Sulfa-trimethoprim combinations can cause reductions in tear production or immune-mediated thrombocytopenia (ITP). Fluoroquinolones can lead to cartilage damage in dogs less than one year of age. It is reasonable to ask your vet for a copy of the package insert when antibiotics are prescribed, or to ask what side effects might occur and what symptoms to watch for so that reactions may be recognized early.
It is possible to help antibiotics to work better by controlling other symptoms of diseases and disorders. Pain relief can provide a great improvement in the patient's ability to respond appropriately to disease by reducing stress levels and providing comfort. Proper nutrition before and during an infection can help to ensure that there will be adequate antibody numbers and that the immune system will be functioning as well as it can. Vaccinations can prevent the primary diseases, such as parvovirus or feline leukemia virus infection that can lead to secondary bacterial illnesses. Resisting the temptation to adopt more than three cats or dogs can keep stress levels and disease exposure in a household to a minimum. I think that pets often do better if they can convalesce from an illness in their own home and try not to hospitalize pets unless it is absolutely necessary.
Antibiotics are among the true miracles of modern medicine. It is hard to imagine having to practice without them. Despite their immense usefulness they are not capable of curing all infections. Bacteria are highly adaptive and they can live in circumstances that prevent the body's immune system from helping the antibiotic work. They may live in tissues that the antibiotic can not penetrate. Viruses are not susceptible to the effects of antibiotics and many diseases and disorders are not caused by infectious agents at all. Antibiotics must be used carefully and they should be used according to established guidelines, unless there is very good reason not to do that. It is important to follow the directions as carefully as possible and to report any unexpected side effects to your vet. Help keep the miracle alive for the next generation!
New Medications and New Uses for Older Medications
There are some new medications that have been approved in the last few months and some older medications for which new uses have been discovered. Perhaps the most intriguing new use for an already approved medication is the continued evidence for selegiline (Anipryl Rx) extending the life span of dogs . This medication received some attention several years ago due to reports that it could extend the life span of laboratory rats that prompted speculation that it may have this effect in humans. Then selegiline was approved for use in treating canine cognitive dysfunction and hyperadrenocorticism in dogs, making it available for use in this species. Now, according to a report in the Bayer Selected Proceedings of the North American Veterinary Conference (Boothe) it has been shown to increase the life span of dogs who receive the medication. I think I might buy some stock in Pfizer if there is further confirmation for this claim.
Meloxicam, a non-steroidal anti-inflammatory (NSAID) medication approved for use for arthritis in dogs in Canada, was recently approved for use in humans in the United States. This will make it possible for US vets to write a prescription for this medication if there are problems with carprofen (Rimadyl Rx) or etodolac ( Etogesic Rx). So far this medication seems to be getting good reviews from Canadian vets. I do not know of plans for a veterinary version of this medication but it is possible that there may be a veterinary version coming.
There have been several articles recently advocating using potassium bromide as the first medication for control of seizures. Potassium bromide is less likely to cause liver damage and it is supposed to be easier on the pet to add phenobarbital to potassium bromide than the other way around, due to a decrease in the sedation when the medications are used in this order. We have not tried this approach yet, in our practice, but it does seem reasonable.
Have you seen the Buspar (Rx) commercials on TV? While those tout human uses, this medication is sometimes successful in controlling urine marking behaviors in cats and can be useful in some cases of aggression between cats. It has to be used carefully for this second effect, because it can also sometimes increase aggressive tendencies.
Puppies with parvovirus often have a difficult time retaining sufficient volumes of liquid in the blood stream to prevent shock. Hetastarch, a colloidal fluid (high molecular weight fluid) has been shown to help increase survival in puppies with this disorder. The newer colloidal fluid, Oxyglobin (Rx), which also carries oxygen, seems to work well in puppies with parvovirus, too. In a switch from the norm, this product is under review for use in humans after being approved for use in dogs.
For dogs and cats with periodontal disease who can not have dental cleansing or who need them very frequently, the use of clindamycin (Antirobe Rx) for five to seven days in a row each month can be very helpful in reducing oral inflammation. This can really improve the quality of life for dogs and cats with this problem.
In the newest Kirk's Current Therapy XII, there is a suggestion to use diphenoxylate/atropine (Lomotil Rx) as the primary cough suppressant in dogs with collapsing trachea syndrome. This is not a widely used medication for this purpose in the United States, but it may be worth considering giving this a try if your dog has collapsing trachea problems that have not been responsive to the more commonly used medications such as dextromethorphan or hydrocodone.
Cyclosporin is used in dogs primarily to induce tear production and decrease inflammation of the eyes in dogs affected by "dry eye" or insufficient tear production. Dogs with this condition have a lot of mucous production leading that people refer to as "sleep in the eye" or "matter" in the eye. This condition is painful and cyclosporin is very helpful in most dogs affected by this condition. It also seems to help to use cyclosporin in dogs with perianal fistulas. This condition occurs most commonly in German shepherds and malamutes in our practice, but may affect other breeds. Prior to the discovery that cyclosporin was helpful, surgery was about the only treatment option. Cyclosporin is effective enough that surgery is rarely necessary, now. There is even some research into using cyclosporin for atopy (allergic skin disease) but I have not seen much information on this. Cyclosporin was originally developed to help prevent graft rejection when people received organ transplants. I didn't think this was likely to be a use in dogs and cats, but with the increase in the number of feline patients receiving kidney transplants, I was wrong.
Enalapril (Enacard Rx) is being used with more frequency in older dogs with chronic renal failure because it seems to have beneficial effects on protein retention and maintenance of urine production. This medication may also be used in cats, but our clinical experience has been that amlodipine (Norvasc Rx) works better in cats for controlling hypertension associated with renal failure and that effect seems to be more important in cats, so we tend to use it first.
Avoiding long term use of cortisones is important, whenever possible, so there are a number of non-steroidal medications currently being used to try to reduce the itching. Cyproheptadine, an antihistamine that is most commonly used as an appetite stimulant in cats seems to help some pets with pruritis. Pentoxyfilline, medication currently being used in humans to control itching in some circumstances is also being tried for pets. Misoprostil, which is a medication usually used to help control ulcers when non-steroidal anti-inflammatory medications are being used, may also help control itching in some dogs, especially when used with antihistamines. It is frustrating to go through a bunch of different medications in an effort to control itching in dogs and cats, but it can be worth the effort when one is found that works well.
Veterinarians treating cats for hyperthyroidism have only had one medication to use for this condition for patients in which surgery or radioactive iodine therapy were not options. That medication, methimazole (Tapazole Rx) has recently been produced in a generic version which should be available to veterinarians at this time. Methimazole is not well tolerated by about 20% of the cats placed on the medication, so this has been a frustrating situation for veterinarians and pet owners, at times. A second medication, ipodate, which has been approved for some time as a contrast agent (dye) for X-rays studies, has been shown to help control hyperthyroidism in cats. Unfortunately, this medication only seems to work for a few months but that provide some recovery time for a debilitated patient prior to surgery and may be helpful in cases in which there may be secondary problems complicating the diagnosis or treatment of hyperthyroidism.
These medications may not be appropriate for all patients affected by the conditions described. However, they are worth considering if your pet is being treated for one of these conditions without much success.
Sheba
I was running along the road two or three miles from my home when I spotted a dog rounding the corner of a home at full speed. I immediately recognized the pit bull look and intensity. In the instant it took my brain to begin to make plans for how to deal with the loss of a portion of some extremity, I noticed that the pit bull was followed closely by two chows. Real fear set in.
I can run pretty fast but I knew I was no match for the dogs. I was concentrating on finding a place to get away and even considering cutting close in front of a car to see if it would eliminate at least one of the dogs when the pit bull passed me.
I recognized her immediately because I had amputated one of her rear legs a couple of years earlier. "Sheba! Do you remember me, girl?" Of course, I was counting on her good will, even though the outcome of her last visit hadn't been all that great for her.
The chows were slower but were gaining quickly, too. Oddly enough, I recognized the lead chow, too. "Jake! How you doing, bud?"
Jake was a regular patient and is a very nice chow, which most vets consider to be a real blessing whenever one comes to the office. I began to relax and hope that I wasn't going to be eaten by a pack of dogs, after all. The dogs ran along beside me and in front of me and all around me, until that became boring. They took off for home.
I was really relieved that the pit bull had been Sheba. I think that most pit bulls are actually pretty friendly towards people but when they are not, they can be terrifying. A pit bull on one of the farms I visited regularly when I was doing large animal work once bit a section of the bumper off my truck. It made me respect their bite strength.
I met Sheba the first time when she arrived at our office after an encounter with a car late one night. One leg was destroyed beyond repair and I had to explain to her owners that she would require amputation of this leg. We checked for internal injuries, as well as we could, made sure she wasn't losing excessive amounts of blood and administered medications for shock and to prevent infection from the severe road wounds. Sheba tolerated our ministrations without complaint.
The next morning we went ahead with the planned amputation. The procedure went well and all of the things we worry about in major surgeries like this failed to occur. No excessive blood loss, no anesthetic crisis and the muscle layers remaining were in good enough shape to provide a good cushion for the small amount of the leg remaining. We were all feeling relieved as we slid Sheba off the surgery table and onto the mobile table to take her back to her cage.
Our relief lasted until the rear leg we had not amputated made it to the edge of the surgery table and then bent 70 degrees before it touched the mobile table. It is amazing how quickly panic can set in. For a brief moment, before I started being rational, I thought that I had amputated the wrong leg. Even after I realized that was impossible due to the injuries to the leg we had removed, I still was terribly upset by the fact that I had just amputated one rear leg and had failed to recognize an obviously severe injury to the other leg. It was especially confusing since Sheba had been standing in her cage that morning.
When we examined the leg after seeing it drop over the side of the table, we discovered that the ligaments on one side of the hock had been torn and that there was just no strength in one direction. I am not sure how Sheba willed herself to stand with this injury but over the course of her life she would show a determination that probably made this problem trivial. We had no choice but to apply a cast to the injured leg and hope that we would not have any complications from doing that. I had never had a patient in which we had to amputate one rear leg and provide external support for the other one.
Sheba seemed hardly to notice. Her owners called us a couple days after the surgery and asked how to get her to stop running around the house with the cast on. Apparently it was causing some problems as it scraped along the walls and furniture as she ran through the house.
We removed the cast several weeks later. Everyone on the staff waited expectantly for some sign that the joint was still weak or had failed to heal. Sheba was unfazed by the worries and immediately began pulling on her leash to leave.
Sheba defended her territory, ran with the local runners and bicyclers and didn't develop any significant problems with the remaining leg until she was almost fifteen years old. Fortunately, she did give up chasing cars after the first accident. Arthritis has set in but it hasn't bothered her attitude at all, so far.
Sheba's owners moved off my running route shortly after the incident in which she led the chows in a wild charge to run with me. She had lots more room to run and no roads to complicate her life. The chows didn't really have any interest in chasing me all by themselves, so my runs went back to quiet uneventful outings.
One last note about online veterinary columns in the veterinary magazines -- despite claiming to have "extensively researched" the available veterinary information sites, not one of the three veterinary magazines featuring web sites this month managed to find ours. We are grateful that our subscribers are better at web searching than the journalists were!
Our site sent about 500,000 "page views" to world wide web surfers last month. We now have almost eight hundred subscribers. We continue to be grateful for your support in our effort to provide a good source of veterinary information to the world's pet owners. We hope you are proud of your contribution to this effort.
The VetInfo Digest is a Publication by
TierCom, Inc.
P.O. Box 476, Route 198
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Opinions expressed are those of the author, Michael Richards, DVM.
Michal Justis, of Fredricksburg VA, is the webmaster for www.vetinfo.com
Copyright 2000