VetInfo Digest March 2005
Table of Contents:
Basic Rules for Medication Use
Antibiotics in General
Antibiotics for Specific Organs or Tissues
Antibiotics for Specific illnesses
This Month's Note:
There has been some controversy in the news lately about the use of brand new drugs by physicians when older and less expensive medications may work as well, or even better. The Vioxx (tm) withdrawal brought a lot of this type of commentary, including advertisements from older pain relievers claiming that the new non-steroidal medications have never been proven to be more effective at pain relief than older NSAIDS. This appears to be partially true -- but one of the reasons is that there is a lack of data about how effective the older medications are, making it pretty difficult to come up with true comparisons. This is less of a problem in veterinary medicine than in human medicine but there are still times when medications are widely used in questionable situations based on ad campaigns from pharmaceutical companies, misleading information from drug reps or just the typical rumor mill that exists in every profession --- including veterinary medicine.
It is surprising how little review of medications occurs after they get approval from the FDA. There isn't any requirement to revisit data after five years or ten years to judge the effectiveness of medications "in the real world," or to adjust package insert regulations to more accurately reflect how the medications are actually being used. The cost of these kinds of reviews almost certainly won't be borne voluntarily by drug companies, especially since the patents are often about to run out on medications that have been on the market for ten years or so. It may be necessary in the future to consider having governmental reviews. Without this kind of information, though, it is sometimes impossible to really know if a medication is actually helpful or to be certain of the incidence of adverse effects. This makes it impossible to come up with a really good risk vs. benefit ratio for many drugs. The bottom line is that you take a risk when you use or give a medication so it should at least seem important or necessary to use it. Otherwise, why take any risk at all for it?
Whenever I talk about the advantages of medications or the proper use of medications it is really important to review just a few things about medicine in general that have to be kept in mind when evaluating the use of any medication.
These are the really important general rules for using and understanding medications. If you keep them in mind it will help a great deal.
Antibiotics in General
Antibiotics are among the true wonder drugs of modern medicine. They have saved countless lives and have contributed to an increased quality of life for many patients who would otherwise have had chronic or even lifelong illnesses. Antibiotics are also among the medications most likely to be used inappropriately. In addition, antibiotics can have serious side effects and in some cases can cause death themselves. With high expectations come frequent disappointments. Antibiotics can't cure everything. They are only appropriate for use to treat illnesses caused by bacteria. Even when used appropriately antibiotics will not always work. When people are disappointed with the effect of antibiotics they sometimes come to believe they don't really work at all. Other times the antibiotics work well but cause a serious side effect that makes some people decide that their use was worse than the original illness. Some people have said this to me even after it was obvious that antibiotics saved a pet's life. There really are times when quality of life can be affected long term when using antibiotics and it is important to recognize this risk but I think that most folks recognize that in life threatening situations it is sometimes necessary to take bigger risks, even though there is a chance they won't always work out as desired.
There is a strong tendency among all practitioners of medicine to use antibiotics when they aren't absolutely certain they are necessary, since the consequences of not using them seem worse. Unfortunately this has contributed to a problem with antibiotic resistance that has been devastating to some human patients and which is beginning to be recognized with increasing frequency in veterinary medicine, as well. It is critical to choose an antibiotic that will actually work against the type of bacteria present, will penetrate the tissue that is infected and that can be used long enough to completely kill the bacteria involved. Making a mistake in choosing the antibiotic or by using an antibiotic for a condition that isn't caused by bacterial infection are both serious errors that usually lead to an unsatisfactory outcome. If an antibiotic is being used inappropriately and then causes a serious side effect, the situation is even worse than when the antibiotic is at least being used appropriately.
Over time a large number of antibiotics have been developed. There is sometimes a tendency to use the "latest and greatest" antibiotic first rather than trying to use antibiotics that have been around for a while. Until there is a known or observed resistance to an older antibiotic in a particular patient, or a recognized problem with antibiotic absorption or distribution that a new antibiotic resolves, there really isn't a big advantage to using a newer antibiotic. It is good that we have lots of choices for antibiotic therapy but there isn't any reason not to try an older antibiotic that usually works before moving on to a newer one, if necessary. Since it is necessary to have a starting point when deciding exactly which antibiotic to use, this is a list of the fundamental rules of antibiotic use for dogs and cats:
Ideally in all circumstances in which antibiotics are used there would first be a culture of the affected tissue or organ and the type of bacteria causing the infection would grow in the culture so that it could be identified. Then testing would be done (sensitivity testing) to determine what antibiotics kill the bacteria involved. After that was done the safest and most effective antibiotic would be chosen from the group of antibiotics that were able to kill the bacteria and reach effective blood levels in the organ or tissue affected. After the antibiotic has had time to produce the desired effects there would be a subsequent culture to ensure that the bacteria were all gone. If the bacteria were not, there would be another sensitivity test to ensure that resistance to the antibiotic had not occurred. This process would repeat itself until it was clear that the antibiotic had successfully killed off the infecting bacteria.
The problems with this ideal scenario are many. Some organs, especially the brain and prostate gland, do not allow much penetration of antibiotics and this limits the choices for treating this areas significantly. If an abscess has formed only a few antibiotics can really penetrate the abscess well. Culturing affected organs can be very problematic, since they are located inside the body, making this a difficult process unless they produce a convenient fluid, like urine, that can be cultured instead. It is easy to contaminate bacterial samples while taking them or to collect a sample that is already contaminated. Identification of bacteria and good sensitivity testing often require the use of an outside laboratory and that means waiting for results. In many situations this simply isn't an acceptable choice and so an antibiotic is selected based on an educated guess. Getting a sample later may not work while the pet is on antibiotics since the antibiotic may work well enough to prevent bacterial growth in the culture even if it isn't working well enough to totally control the infection in the pet. With all these possible negatives it becomes more common for veterinarians to put pets on antibiotics based on other factors, such as cost, availability, past experience and charts of the usual antibiotics that will work for specific diseases, organ systems or situations. When this system isn't working, though, it is really important to consider going back to the beginning and getting a good quality culture sample to identify the bacteria involved and make a plan for eliminating it.
Despite the fact that most antibiotic use is less than perfect from a scientific viewpoint there are some practical rules for antibiotic use based on science that are beneficial if they are kept in mind:
Since antibiotic culture and sensitivity testing isn't always possible, a number of lists of recommended antibiotics most likely to work when it is necessary to start treatment without culture results have been compiled. These lists vary some depending on who compiles them but I have tried to come up with my own list that includes the medications most commonly agreed upon, rather than trying to come up with a comprehensive list of possibilities. I have done this because it is apparent that in some cases when people write to me, pets are on medications that may not be effective for the pet's particular condition. This can happen because a veterinarian believes strongly in the usefulness of a particular antibiotic, due to cost concerns or for a number of other reasons. If your vet has varied from these guidelines it is entirely possible that there is a good reason for having done so. However, if your pet has a problem confined to an area for which there is a list of generally recommended antibiotics and the response to the antibiotic is less than expected it can be helpful to check and see if there is a chance the antibiotic just isn't appropriate. If you find that the antibiotic is expected to be helpful then you know that it may be necessary to make a really concerted effort to identify the bacteria causing the pet's problems and to choose an antibiotic based on sensitivity testing. While this is more trouble and can be costly at times, it can also be the difference between success and failure in treating a pet's medical problems.
Note that ALL antibiotics used for pyoderma (bacterial skin infection) in dogs should be used at least 3 weeks! The reason for this is that it takes about 3 weeks for the skin cells to be fully replaced and treating this long helps to limit the incidence of infections managing to survive and infect new skin cells as they form.
Antibiotics generally recommended for use in skin disorders with a bacterial component:
Cephalosporins (most commonly cephalexin (Keflex Rx), cefadroxil (Cefatabs Rx) or cefpodoxime (Simpicef Rx) but there are many others)
Amoxicillin with clavulanic acid (Clavamox Rx)
Potentiated sulfa dugs (Tribrissen (Rx), Bactrim (Rx), Primor Rx, sometimes the generic is abbreviated "smz-tmp".
Clindamycin (Antirobe Rx, Cleocin Rx)
Erythromycin (almost always generics)
Antibiotics for skin disease sometimes take an extremely long time to work really well. It is not unusual for primary bacterial pyoderma to use antibiotics for 3 to 6 months or more. Some dogs require lifelong antibiotic therapy. In general it is acceptable to use antibiotics at lower than usual doses or at less frequent dosing intervals to suppress bacterial growth when it is necessary to use them for really extended periods but it is important to be sure that the condition is controlled before making this change.
Long term use of antibiotics for skin conditions can sometimes contribute to the development of yeast infections (Malassezia species). It is sometimes necessary to use corticosteroids such as prednisone to control skin itchiness while also using antibiotics. In these circumstances it is important to remember that antibiotic use might be necessary for a much longer time.
Urinary Bladder Infections
In general for the first instance of bladder infection it is acceptable to use antibiotics for 2 weeks, although longer is OK.. If cystitis recurs antibiotics should be used for at least 4 weeks and preferably 6 weeks. Ideally the cessation of antibiotics should be based on obtaining two consecutive negative urine cultures, at least 2 weeks apart. The most common causes of recurrent bladder infections when antibiotics are being used in dogs are bladder stones, bladder cancer and hormonal diseases, especially hyperadrenocorticism and diabetes.
The most common causes of recurrent bladder problems in cats is lower urinary tract inflammation due to interstitial cystitis, struvite (MAP, triple phosphate) crystals. This means that the most likely cause for antibiotics not to work well in cats with lower urinary tract disorders is simply that they aren't necessary because the problem is not bacterial infection. It is estimated that less than 5% of cats less than 10 years of age who have signs of urinary tract discomfort or blood in the urine actually have bacterial infections of the bladder.
Antibiotics most commonly recommended for use when there is a urinary bladder infection (cystitis):
Potentiated sulfa drugs ( Tribrissen Rx, Primor Rx, many generics, often labeled SMZ-TMP)
amoxicillin and amoxicillin/clavulonic acid
fluoroquinolones ( enrofloxacin = Baytril Rx, orbifloxacin = Orbax Rx, difloxacin = Dicural Rx, marbifloxacin = Zeniquin Rx)
tetracyclines, usually doxycycline (almost always generics), primarily for suspected Pseudomonas infections
Upper Airway Disease (nasal passages, pharynx, larynx, trachea)
Bacterial upper airway infections in dogs are not common. Most of the time signs associated with infection of the upper airways is due to something other than bacterial infection. In cats it is not uncommon to see mixed viral and bacterial upper airway infections. Treating the bacterial component appropriately can lessen clinical signs and prevent damage to the nasal lining. One of the causes of persistent upper airway infections in cats is early damage to the nasal passages leading to long term immune compromise and persistent or recurrent upper airway infections.
There is increasing evidence that administering medications through a nebulizer is more effective for airway infections and also allows the use of antibiotics that aren't easily administered in other ways due to the need to inject them. Nebulizers for cats and dogs are now available at a cost that makes them practical to use when necessary. Nebulization allows the use of the aminoglycoside antibiotics amikacin and gentamicin which would other wise have to be injected daily and it also limits the potential for side effects from these antibiotics, as well. These antibiotics are not included in the following list which includes antibiotics likely to be sent home for oral use. Antibiotics most commonly recommended for use in upper airway infections (runny noses, pharyngitis, laryngitis):
amoxicillin or amoxicillin/clavulonic acid
chloramphenicol -- note that handling chloramphenicol is a risk to humans susceptible to reactions!
azithromycin (Zithromax Rx) -- useful for chronic upper airway infections in cats and dogs
Antibiotics most commonly recommended for lower airway diseases ( chronic bronchitis, pneumonia):
Note that antibiotics used for pneumonia should be used until there is no visible sign of pneumonia on follow up X-rays. It isn't unusual for this to take as long as 6 weeks. Nebulization can be helpful in lower airway disease but can't totally replace oral or injectable antibiotics for these conditions, as it can for upper airway disease. Using something to break up mucus and inflammatory debris in the chest can make it easier for the antibiotics to get to the bacteria involved.
Metronidazole or ampicillin/sulbactam (Unasyn Rx), which can kill anaerobic bacteria, is often combined with one of the following:
aminoglycosides (gentamicin = Gentocin Rx, amikacin = Amiglyde V) -- these must be given by injection
amoxicillin and amoxicillin/clavulonic acid
Antibiotics more likely to be used alone for lower airway disease:
potentiated sulfa (sulfa + trimethoprim)
fluoroquinolones (although these are also often used in combination with other antibiotics)
Antibiotics most commonly recommended for oral infections:
doxycycline (there is a doxycycline gel that can be applied directly to pockets of periodontal disease).
Antibiotics most commonly recommended for inflammatory bowel disease:
Note that in this case antibiotics are frequently used for a condition that isn't strictly a bacterial illness. This is done due to the potential for changes in bacterial populations to occur in the intestine in the face of other illnesses or disorders. Controlling these population changes can be helpful in limiting diarrhea or vomiting.
Tylosin (Tylan Rx -- a powder approved for use in pigs)
Tetracyclines (including doxycycline)
Metronidazole (Flagyl Rx)
Sulfasalazine (Azulfidine Rx)
Antibiotics for bacterial infections of the small intestine (enteritis):
amoxicillin, sometimes in conjunction with metronidazole
Antibiotics most commonly recommended for colitis:
potentiated sulfas (acute colitis)
sulfasalazine (chronic colitis)
amoxicillin (if Clostridium perfringens is suspected)
Antibiotics most commonly recommended for prostatitis:
Note that the primary problem with treating prostate infections is choosing an antibiotic that can actually achieve good levels in the prostate gland. When the gland is acutely infected a broader number of antibiotics can be used because more antibiotics are capable of getting into the prostate tissue when it is inflamed. Unfortunately, once the antibiotic starts to work well and the inflammation subsides then antibiotic no longer works well because it isn't absorbed into the prostate gland, so it is sometimes necessary to change antibiotics for long term management of prostate disease.
tetracyclines (including doxycycline)
Antibiotics that are questionable for use in prostate disease due to inability to penetrate the prostate gland:
Antibiotics with a particular affinity for working well in very specific circumstances:
Chronic rhinitis (nasal infection) in cats will often respond better to azithromycin than to other antibiotics.
Cephalosporins used with metronidazole seem to be able to penetrate interdigital (between the toes) cysts better than individual drugs. Another choice for this condition is enrofloxacin mixed with a carrying agent like DSMO or Synotic Rx and applied topically.
Clindamycin has a good reputation for working well in bone infections and severe periodontal disease.
Doxycycline works well for rickettsial infections (not technically a bacterial infection) and for l-form bacterial infections in cats. The l-form bacteria are very difficult to culture and so it is sometimes necessary to simply use antibiotics to rule the infection out even though this isn't ideal from a scientific point of view.
In sudden onset (acute) kidney failure it is necessary to consider the possibility that leptospirosis, a bacterial infection, has caused the kidney failure. It is usually considered to be safe to use amoxicillin or ampicillin, which can kill leptospirosis, until it is possible to obtain an accurate diagnosis for the cause of the kidney failure.
Borreliosis (Lyme disease) responds to doxycycline, amoxicillin, azithromycin or cefatriaxone, although there is some controversy over whether doxycycline works against borreliosis or just kills infections easily confused with it such as ehrlichiosis or other rickettsial diseases.
Needle-less vaccination for feline leukemia virus is now available. Purevax Recombinant Leukemia (tm), a non-adjuvented vaccine, is now available from Merial (tm). This new vaccine is thought to be less likely to cause vaccine associated cancer than injected feline leukemia vaccines that include an adjuvent. An adjuvent is an irritating substance meant to improve the reaction to the vaccine. The vaccine is sprayed through the skin using a special vaccination device. If your cats are at risk for feline leukemia it would be worth thinking about the use of this vaccine.
Enisyl-F (tm) is a new formulation of l-lysine for people who are giving l-lysine to their cats to help control chronic herpes virus. It is a gel rather than a tablet or powder and comes in a dosing syringe to make it easier to use. This is more costly than the tablets but it does provide an alternative for cats who are hard to medicate.
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The opinions expressed in this newsletter are those of Michael Richards, DVM., author.
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