Under the Microscope: Antibiotics
Posted Apr 01, 2006 - written by Kathy Wilson.
Bacteria are everywhere—around us, on us, inside us. Most of the time we donʼt know they are there. In sheer numbers and variety they are astounding. But itʼs their ability to reproduce themselves with incredible speed, spawning whole new generations in a matter of minutes, that enables them to invade and overrun their host before the immune system has time to marshal its defenses.
Only about 10% of bacteria cause disease, and many of these are harmful only some of the time. In fact, some bacteria are so helpful to us that we canʼt live without them. Some are helpful when they stay in their normal habitats, but cause real problems when they turn up where they donʼt belong. For example, take the infamous E. coli (Escherichia coli, of which there are many strains, most quite harmless). In the intestines, E. coli helps us digest our food; but if it strays elsewhere in the body it can cause critical illnesses in humans and wolfhounds alike.
Some bacteria use oxygen for metabolism; these are called aerobic. Others, like botulism and tetanus, do not use oxygen. These are called anaerobic. Bacteria are classified as gram positive or gram negative based on their appearance when treated with a dye called a gram stain. Streptococcus pneumoniae (strep) and staphylococcus aureous (staph) are common examples of gram positive bacteria. E. coli and salmonella are common examples of gram negative bacteria. Often, different medicines are needed for gram negative than for gram positive infections. Bacteria can be aerobic or anaerobic and either gram positive or gram negative.
How Antibiotics Work
There are two major ways that antibiotics work. Bacteriostatic antibiotics work by keeping bacteria from reproducing. Bacteria reproduce so rapidly that slowing or stopping their reproduction gives the host (your wolfhound) time to get its immune system into high gear to fight off the infection. Bactericidal antibiotics actually kill the bacteria. In high concentration, most bacteriostatic antibiotics are considered bactericidal. However, in low concentrations, bactericidal antibiotics are only bacteriostatic. Adequate dosage is important!
Which Antibiotic to Use When?
Choosing an antibiotic is not necessarily simple. Your vet must also evaluate your houndʼs symptoms, age, overall health, and any previous problems the hound has had with medications. In addition, your vet needs to consider these issues.
An antibiotic that is effective against many different bacterial infections is called broad-spectrum. If your hound is very ill, your vet will prescribe a broad-spectrum antibiotic, hoping it will “cover” the exact cause. Your vet may, in the meantime, run tests to determine the exact type of infection, but when a hound is very sick, it is not safe to wait for test results, which can take days.
Antibiotics may not be equally effective in all parts of the body. Some antibiotics work very well for infections in the intestines, for instance, but they donʼt get “into” the lungs very well and therefore would be bad choices for pneumonia.
Culture and Susceptibility
Culture and susceptibility is a test that determines what bacteria are causing an infection, and what antibiotic or antibiotics will work well against these specific bacteria. This test generally takes one to four days to produce results, which is why it is unsafe to wait for final results if your hound is gravely ill.
Combination Therapy: Synergy vs. Antagonism
Sometimes antibiotics with different mechanisms of action are combined in order to boost their bacteria-killing power, broaden their spectrum of activity, or to overcome bacterial resistance. This chemical effect is known as synergy. Other antibiotics should never be combined, because they are antagonistic, which means they decrease or cancel out each otherʼs effectiveness. You should always discuss with your vet any medications you have given your hound, to avoid the chance of an antagonistic combination.
Antibiotics are frequently grouped into classes based on their chemical structures. Those in the same group generally work in very similar way.
The following antibiotics are grouped by class, progressing from first-line choices to those usually reserved as last-chance drugs.
Penicillins were the first antibiotics introduced. The drug most familiar to us, Amoxicillin, is effective against many different bacteria including Pneumonococci, Streptococci, and certain strains of Staphylococci. The drug Clavamox (or Augmentin, in the human formulation) is Amoxicillin with a
chemical called sodium clavulanate added during manufacturing. Clavamox is effective against a wider range of bacteria than Amoxicillin alone. Penicillins and Clavamox are widely prescribed as a first line of defense for respiratory, urinary tract, and soft tissue infections. Penicillins and cephalosporins are both members of the beta lactam class of antibiotics.
Sulfa drugs were among the earliest antibiotics used, and they are still widely prescribed, in part because of their low cost. Combining certain sulfas with drugs like Trimethoprim increases their usefulness. These combination drugs (such as SMZ-TMP and Bactrim) provide synergistic action against a variety of pathogenic bacteria. Sulfa drugs can cause worrisome side effects, including joint inflammation and hepatitis, and can interfere with blood tests to determine thyroid levels.
Cephalosporins are broad-spectrum antibiotics, initially developed to treat penicillin-resistant infections. Cephalosporins treat a wide variety of infections, from respiratory to urinary tract, and are often used for surgical prophylaxis. These drugs are further classified into ʻgenerations,ʼ with each successive generation adding a broader range of effectiveness. First-generation cephalosporins include the familiar cephalexin (Keflex) and cefazolin (Ancef). These drugs are frequently prescribed as a first line of defense.
Tetracyclines make up a group of broad-spectrum antibiotics which includes doxycycline. “Doxy” is widely considered the drug of choice for treating Lyme disease, a tick-borne illness caused by the bacteria borrelia burgdorferi. Doxycycline is used for other infections as well, notably brucellosis.
Metronidazole (Flagyl) is an antibiotic especially effective against anaerobic infections. It is also effective against certain protozoal infections, especially giardia. Metronidazole is a very effective anti-diarrhea medication because it reduces inflammation in the bowel. Metronidazole is often prescribed for colitis, which may or may not be caused by inflammatory bowel disease.
Macrolides are used to treat certain respiratory and soft tissue infections. The newer members of this group, such as azithromycin (Zithromax) and clarithromycin, are known for their particularly high levels of lung penetration, as well as activity against some bacteria which are resistant to penicillin, including mycoplasma. Tylosin (marketed as Tylan) is a macrolide approved for use in farm animals. Although it is not labeled for use in dogs, veterinarians frequently prescribe it to treat chronic colitis; Tylan may be effective even if other treatments have failed.
The fluoroquinolones are broad-spectrum antibiotics that can be used to treat intracellular infections, such as those caused by brucella and mycobacteria. Baytril (enrofl oxacin) and Zenaquin (marbofloxacin) are the most commonly chosen fluoroquinolones in veterinary practice. They are not usually used as a first line agent, but reserved for more serious illnesses. Young dogs should probably not receive fluoroquinolones, since cartilage lesions have been reported as a side effect in immature dogs.
The drug ciprofloxacin (Cipro) does not have FDA approval for use in animals, but is prescribed by veterinarians “off label,” no doubt in part because the generic formulation is less expensive than veterinary fluoroquinolones. However, some pharmacologists believe dogs do not absorb Cipro nearly as well as humans do, and may not be getting the desired benefit. Physicians and veterinarians generally agree that Cipro should be reserved for patients who have failed at least one prior therapy.
Bacterial resistance to the fluoroquinolones is a very real and increasing problem. Some strains of streptococcus pneumoniae (a.k.a. pneumonococcus) and salmonella are now resistant to fluoroquinolones, meaning that these drugs no longer are effective against them. Some scientists estimate that this entire category of medications will be totally ineffective in as little as five years if current resistance trends continue.
Clindamycin (Antirobe) is highly effective against anaerobic bacteria, and its ability to penetrate bone and soft tissue makes it a good choice for dental disease, osteomyelitis (bone infection), and skin wounds and abscesses. Depending on results of culture and sensitivity tests, some veterinarians prescribe Antirobe in combination with Baytril to treat pneumonia.
Gentamycin, neomycin, and kanamycin are widely-used aminoglycoside antibiotics. Wolfhound owners probably encounter these drugs most often as topical preparations (ointments or drops) for ear or eye infections. Systemic use of aminoglycosides is reserved for very serious infections, since they must be administered intravenously and can have potentially serious side effects. They are frequently combined with beta-lactams (penicillins or cephalosporins).
Imipenem (Primaxin) is an intravenous antibiotic which has a broad spectrum of activity against aerobic and anaerobic gram positive as well as gram negative bacteria. It is not labeled for veterinary use, and is a last-chance drug, given only when other therapies have failed.
Vancomycin treats certain infections caused by gram positive bacteria. Vancomycin is not labeled for veterinary use, and must be given intravenously. It is very powerful and very expensive, and is considered a last-chance drug, used only after treatment with other antibiotics has failed. Some bacteria have become resistant even to vancomycin.
Linezolid (Zyvox) was introduced in 2000 to treat antibiotic-resistant strains of gram-positive bacteria, such as streptococcus pneumoniae. It is not labeled for veterinary use.
The ability of bacteria to adapt to their environment—an environment that now includes many different types of antibiotics—has levelled the playing field in ways that public health authorities never dreamed possible. Bacterial strains resistant to antibiotics are now commonplace in hospitals, and have made some common infections (like ear infections in children) more difficult to treat than they were ten or twenty years ago.
Resistant strains of bacteria are having an impact on veterinary care as well. In the second half of this article, we will take a look at the growing problem of resistance. How does it affect our wolfhounds, and what can we do to avoid making it worse?
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