The primary reason antimicrobial drugs are given to beef cattle is to treat or control respiratory disease, though other conditions (such as foot rot, pinkeye, wooden tongue, diphtheria, etc.) are also treated, to help the animal fight off bacterial infection. Kelly Lechtenberg, DVM, PhD (consulting veterinarian at Midwest Veterinary Services in Oakland, Nebraska) specializes in bovine medicine and has worked with many issues regarding use of antibiotics. “The BRD (bovine respiratory disease) complex is a syndrome that is usually a bacterial infection combined with viral infection and various stress factors,” he says. Viruses are not affected by antimicrobial products, but antibiotics are usually given to the sick animal to control or prevent secondary bacterial infection.
The most commonly used products today include Draxxin (Pfizer), Nuflor (Schering-Plough), Excede (Pfizer), Baytril (Bayer), Micotil (Elanco), LA-200 (Pfizer), Tetradure 300 (Merial), Naxcel (Pfizer) and various brands of penicillin and sulfa. A few stockman also use tylosin or erythromycin (which are both macrolide antibiotics).
Draxxin (tulathromyicin, which is also one of the macrolides) is one of the newer products and is a long-acting drug that has been very useful for combating respiratory disease. It is labeled for use both as a therapy and as a control (to prevent disease). “We can legally administer this product to cattle that we as veterinarians believe are at risk of developing disease,” explains Lechtenberg. For instance, it can be given to stressed animals after a long transport, upon arrival at their destination.
“Draxxin carries a bovine respiratory disease label and could be used at weaning if calves are stressed, especially in large cow-calf operations where even though it's a closed herd large groups of calves may be co-mingling—not from different sources but from different ranches in their own operation. There might be significant trucking and stress moves,” he says.
“The duration of effectiveness for this drug is at least 10 days. People ask, ‘How long after I administer Draxxin can I be comfortable that we still have therapeutic levels in the lung, or when should I have to re-dose?' I typically don't think of Draxxin as a product you'd want to re-dose with. If the animal has not responded adequately in that length of time and you feel it needs additional treatment, it is probably better to switch drugs and go to a different class of antibiotics. This is not a universally held opinion; this is my own opinion,” he says.
“In the same drug class (macrolides) we also have Micotil (tilmicosin). It's been around longer, is also a long-duration therapy product (at least three or four days) and has a slightly different spectrum than Draxxin, but they are generally used for treating the same types of condition. One cautionary note with Micotil is human safety considerations,” he says. Micotil can be fatal to humans if accidentally injected.
Both Draxxin and Micotil are prescription products (you need a prescription to get them), and the producer must be working with a veterinarian for proper diagnosis and treatment recommendations, so a veterinarian will be giving the drug or instructing the client in its proper use. This is especially important for the cow-calf operation, where the stockman may be putting a syringe in a saddle bag or taking the drug to treat one calf—often grabbed in the pasture or crowded into a gate corner or wherever you can get hands on the animal—without ideal restraint conditions. A feedlot operator, by contrast, will be putting the animal in a treatment facility where there's less risk for struggle and accidental injection of a human. “If I were to poke myself accidentally with a drug of the macrolide class, I would rather poke myself with Draxxin,” says Lechtenberg. “It does not have human health implications.”
Another macrolide is erythromycin, but it isn't used as often because it is very irritating to muscle tissue. “The only label way it can be used is intramuscular. I sit on the Beef Quality Assurance task force for the NCBA, and in my opinion there is no place for injectable erythromycin in modern therapy,” he says.
Another drug that has approval for use in respiratory disease is Nuflor (florfenicol) which is in a different class of drugs—the same class as chloramphenicol, which is no longer allowed for use in food animals. It's a different class of drugs, very effective and broad spectrum. “All of these drugs we've talked about so far are injectable, to be administered subcutaneously (except for erythromycin), in keeping with NCBA's guidelines for beef quality,” he says.
Nuflor's effective duration of activity is probably at least 4 days. “It's slightly shorter than Draxxin. The main question stockmen or feedlot cowboys ask, for any of these drugs, is how many days should they watch the animal (for response/improvement) before they switch drugs. I'd give Draxxin at least a week (up to 10 days), Micotil three days and Nuflor four days,” explains Lechtenberg. If the calf is slipping backward—not making progress in recovery, you need to re-evaluate the diagnosis. Is this in fact respiratory disease or does the calf have other issues?
“It may be a primary viral infection, and the antibiotic is good to have (to keep bacterial load down) but the real problem is viremia. In that instance, changing antibiotics won't do much good. Or, you may have a chronic condition in the lung (especially in feedlot cattle) and the antibiotic isn't effective,” he says. In the cow-calf operation this is generally not the problem, since the stockman will usually be dealing with a calf that's sick for the first time. In that instance, you generally expect the response to be pretty good.
The cephalosporins are another class of drugs, introduced about 20 years ago. These include Naxcel, Exenel and Excede. “Naxcel is very short acting (about 1 day) but a wonderful product in respect to residues. There's either zero or very short withdrawal time with these drugs. They are in the same general class with penicillin, but are much more potent and much more broad spectrum than the base compound of penicillin. They are very good for respiratory disease and foot rot. Treating foot rot is one of the big uses for cephalosporins because this keeps your slaughter options open for adult cows,” he says. If an older animal gets foot rot and you want to try therapy, but realize that you might have to butcher or sell the animal, you won't have to wait so long on withdrawal time.
“The products that are labeled for foot rot include LA-200, Nuflor and several others but many of these have significant withdrawal time. If they don't get the job done and you have to hang onto the animal longer than you want to, the cephalosporins are a better choice,” explains Lechtenberg.
The cephalosporins all consist of the same chemical entity—ceftiofur. “These drugs include Naxcel, Exenel, (effective duration about 2 days) and the newest one Excede. The latter is a different formulation, in a different carrier, so it has a longer duration of effectiveness than the others. The mechanism by which that happens is different than in Draxxin or Micotil which are absorbed rapidly and then concentrate in the white cells of the body. Excede is absorbed more slowly, so it's like giving a continuous slow-release dose. It is effective for about 10 days, very similar to Draxxin and is also a good drug to give cattle upon arrival at a feedlot, for instance,” he says. Naxcel would be the drug of choice when treating an adult cow (if it's an animal you could put in the chute again for retreatment if necessary, and to take advantage of the short withdrawal time if you decide to sell or butcher her afterward), whereas Excede might be what you'd choose when receiving calves into a feedlot—where you want to bring them in, process them and let them get used to the feeding program and not have to handle them again. There are many choices of antibiotics today, to give a producer more options to best fit a particular situation.
“When setting up a program and deciding whether to use Draxxin or Excede as your long-action drug—in my experience one thing to consider is that Draxxin is pretty good in operations that are having problems with Micoplasma bovis. Some farms and herds have had a serious problem with this, while others have never heard of it. We started seeing M. bovis in the late 1980's, primarily in northern and western ranch cattle, and now we're seeing it more commonly in some of the highly put together southeastern cattle. Draxxin is pretty effective against this pathogen. Excede has a similar duration of efficacy, but because it is a cephalosporin (drugs that work by inhibiting the formation of bacterial cell walls) it doesn't work at all for M. bovis because micoplasmas do not have a cell wall,” explains Lechtenberg.
Thus your choice of antibiotic would depend on the history of disease on your ranch. If you struggled last year at weaning time with Micoplasma bovis, and you decide to dose the calves at weaning this year to head it off, you'd want to use Nuflor, Draxxin, LA-200 or one of the other drugs that have efficacy against this type of bacterium. “You might have the luxury of susceptibility data from last year (if your veterinarian cultured the organism), or you might not and are just playing a hunch. There's no guarantee that you'll encounter the same bug, but these decisions should be made with the producer and veterinarian working together and planning a strategy—such as maybe backgrounding the calves in smaller groups before co-mingling them. There are many steps that should happen before you decide to just give every calf antibiotics,” he says.
Another class of antibiotics is the floroquinalones, which includes Baytril (enrofloxacin) and A180 (danafloxacin). “These are different variations of this class, and both are very effective and very potent. The parent compound is ciprofloxacin, a human antimicrobial that is very popular.” This is a broad spectrum antibiotic effective against some strains of bacteria that have developed resistance to penicillins and cephalosporins.
“Baytril and A180 have some restrictions, which producers need to remember. They carry warnings on the label, saying it is illegal to use them in any extra-label fashion, such as for baby calf diarrhea. These drugs are low volume injections and very effective against E. coli and salmonella, but the reason they are illegal for this use because there is concern about development of antibiotic resistant gut bugs (enteric pathogens) that can infect people. These drugs can be used for baby calf pneumonia (they are labeled for treating pneumonia in beef cattle) but not for scours,” he points out.
All of these newer drugs require a prescription from your veterinarian. You should not be using them without advise from and consultation with your vet. The only drugs you can legally purchase over the counter without a prescription (from a feed store, catalog supply company, etc.) are penicillin, sulfa and the tetracyclines. “There is some talk that this will change, but at this point in time they can be purchased over the counter,” he says.
The Old Reliables -- Most ranchers are very familiar with the traditional drugs that have been in use a long time, like sulfa boluses, LA-200, penicillin, and injectable tylosin. “These drugs are a little bit like your old computer, regarding what they can do. They haven't gotten worse (or ineffective); they still do for you what they did in earlier years, but the new ones do more,” he says. On many farms the combination of LA-200 and sulfa still work to combat respiratory disease.
“Many farms or ranches have not had the pressure experienced by large feeding operations—that are always bringing new cattle in, with relatively higher exposure to antibiotic resistance development, with a lot more pathogens than you have on the home farm. The feedlot animal has more stressors, and these are cattle we're putting a lot of antibiotics into, even though we all know that the body's immune system is what ultimately determines whether the calf responds to our therapy or not. All we are trying to do is give the animals another crutch to help fight disease, even though they will succeed or fail on their own ability to fight off the infection,” says Lechtenberg.
Some of the older, less expensive products still do have a place. If they still work on your ranch, there's no reason to not use them. If they don't work very well, then you can switch to the newer, more expensive drugs. “The rule of thumb in the feedlot world is that we shoot for about an 85 to 90 percent success rate (response to therapy, in the animals treated). In the cow calf world, however, this is not good enough, but to expect 100 percent response rate is unrealistic. In the cow-calf environment, regarding respiratory disease, if you are getting 95 percent success in response to therapy, this is great, and I wouldn't go changing antibiotics. We expect some cattle to fail, and the first time you have a calf that needs re-treated doesn't mean you had antibiotic failure,” he explains.
“Your veterinarian should be involved in this process—for diagnosis and treatment recommendations. Generally speaking, if the cattle are responding well to an inexpensive program, with low relapse rate, there's no need to change just because there's a newer antibiotic available,” he says.
One of the newer formulations of oxytetracycline is Tetradure 300. “This is injectable oxytetracycline that contains 300 milligrams per millileter, compared to Biomycin 200, LA-200, generic equivalents, etc. It's not longer-lasting but is more potent, so you can give a smaller volume dose (and thus less risk for tissue irritation and reaction). The idea was to give the same amount of drug in less volume. The potency has to do with the characteristics of the antibiotic. The most potent products we have are like Draxxin, in which you can treat a very large animal with just a 10 cc syringe,” explains Lechtenberg.
The drug companies have focused on several things in creating various products, not only looking at the spectrum of activity (the types of bacteria the drug will kill) but also putting the drug into carriers that don't make excessive volume. “What we really want is low volume products because they are less likely to cause injection site reactions (and are more efficient to store and ship and administer) and less likely to be painful to the cattle we give them to. We like low-volume products that are also safe, in case people accidentally inject themselves. We also want a high margin of safety for the cattle, in case we happen to overdose them,” he says.
Tylan-200 (tylosin) is still available (Elanco). “When given intramuscularly it is very irritating to the tissues. There are some programs that still use a significant amount of tylosin intravenously. I think the IV usage is extra-label but there is good data on its effectiveness against pneumonia. The most common use of that drug, however, is in feed to prevent liver abscesses, and it is sometimes used in a salt/mineral product for pinkeye control. There's also a powder form used for pinkeye treatment in baby calves. But there's probably a lot more sulfa used, in the form of boluses for baby calf diarrhea, and boluses for pneumonia and foot rot,” explains Lechtenberg. There are also some combination therapies such as long-acting sulfa boluses given in conjuction with LA-200 to give 3 days' worth of coverage.
There are many options, today, and more choices for selecting a product that fits a specific need. “When I graduated from veterinary school we only had the penicillins, sulfas and tetracyclines. This is why there were many products used extra-label. We'd get together and talk about how we could mix this or that, to address a particular problem. But compounding is not very acceptable anymore because there are so many good products today that are safe. It's difficult now for me or any other veterinarian to justify batching something up in a clinic since it wouldn't be any better than what's already available,” explains Lechtenberg.
There are very few toxicities in doubling up the drugs that are available, but the biggest reason to not do combination therapy today is that it would usually double your bill. “With the modern therapies available we do a lot less combinations than we did in the past,” he says.
Penicillin is still used, but one of the biggest concerns about penicillin is that it generally needs to be given in higher than label dosage to be effective. Even though you can purchase it over the counter, in order to use it extra-label you need to have a prescription from your veterinarian. Almost everyone who uses penicillin gives it several times the labeled dosage, since this is the only way it's effective for certain conditions.
“It was labeled using a septicemia model. The cephalosporins are in the same drug class as penicillin. They are all absorbed quickly from the tissue into the bloodstream. A calf with pneumonia needs it in the lung tissue, not the blood. This class of antibiotics concentrate in the blood, so when drug companies were doing the efficacy tests, they were modeled on blood borne infections (septicemia). So they came up with very low doses; it doesn't take very much penicillin to treat septicemia. But in reality we don't treat much septicemia in cattle. We treat foot rot, pneumonia, pinkeye, etc. In order to get effectiveness for these conditions, we have to drive the blood concentration very high so we can get spill-over effects into the tissue. Then it works well,” he says.
“Penicillin is safe. It's not toxic, so there's no problem with giving high doses. But since this is extra-label, someone must be responsible for residues.” Thus you need to work with your veterinarian for proper withdrawal time for the higher dosage.
“One of the things that can happen with penicillin is that it's one of the most common allergenic antibiotics. Some people are allergic to penicillin and its derivatives, since it is often used in human medicine,” he says. Since it is usually administered in the muscle, if you give a calf 5 times the label dosage and only observe the normal label withdrawal time, there will be residue in the muscle if that calf is butchered too soon.
“If the neck muscle is ground into hamburger and contains residue, somebody somewhere who eats that meat may react, and may go into anaphylactic shock. A calf might go into shock if given a second dose; it's very allergenic. So this is a caution when using penicillin, even though it can do a good job on foot rot and some cases of calf pneumonia. But in order to get tissue levels high enough, you have to use so much that it's almost cheaper to use one of the newer drugs. For clostridial infections, however, penicillin would be the drug of choice. At label dose, penicillin would be very effective against clostridia,” says Lechtenberg. Thus you need to be working with your veterinarian to diagnose and treat various conditions, to know which antibiotics and dosages would be most appropriate.