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APPLIEDSCIENCE By Daniel Scholl, Herman Barkema and Julie Baillargeon Rational antibiotic use Consumer concerns about resistant bacteria prompt research into ways producers can use antibiotics more effectively when treating mastitis oug Morrison is the third generation on the family farm tucked into the Kingsbury hills between Drummondville and Sherbrooke, Que. In Doug’s grandfather’s day, on-farm medicine cabinets did not even contain antibiotics. Now, 60 years after the development of the first treatment against mastitis, antibiotic resistance has become a source of concern for the Morrisons and dairy producers across Canada. Doug, who operates Malboro Holsteins with his wife, Hilda, has been a member of the Canadian Bovine Mastitis Research Network (CBMRN) scientific committee for the past four years. He and Hilda have 125 Holsteins, including 40 milking cows. The voice of dairy producers on the CBMRN committee, Doug communicates their mastitis research needs and priorities. During discussions, he and his fellow producers in the network have stressed the importance of addressing antibiotic resistance in the CBMRN’s research programs. Producer interest in antibiotic resistance stems mainly from consumer concerns, he says. The public is often exposed to media reports on such issues as genetically modified organisms, mad cow disease and a bacteria linked to antibiotic resistance known as C. difficile, which can cause serious intestinal illness. Regardless of whether a problem is real, media coverage has raised con- D 34 | November 2007 | MilkPRODUCER sumer awareness of these topics. Ordinary Canadians are asking more questions about the origin and quality of the food on their plates. Dairy producers are sensitive to consumer opinions and do everything they can to produce safe milk that meets consumer expectations, Doug says. “As a producer, I take great pride in offering a high-quality prod- uct. The quality of the milk really is a priority for us, and it’s a topic that’s raised at almost every one of our (Quebec milk producer) federation meetings.” It’s highly improbable that dairy products containing antibiotic-resistant bacteria could ever reach grocery stores. Producers routinely discard milk from cows that have clinical mastitis. Moreover, pasteurization effectively Quebec dairy farmer Doug Morrison voices producer concerns to researchers. eliminates bacteria—even bacteria that may be antibiotic resistant. Antibiotic use on the Morrison farm is mainly associated with mastitis, as it is on most Canadian dairy operations. Whether they are used for treating clinical cases or for dry cow therapy, antibiotics are a valuable tool for helping producers better control mastitis in their herds. However, Doug has doubts about their efficacy. “It seems to me that we’ve been using the same antibiotics for decades and we’re still having the same problem controlling mastitis,” he says. “Are the antibiotics becoming less effective?” If mastitis were caused by a bacterium resistant to a particular antibiotic, any treatment using it or a similar antibiotic as the active ingredient would be ineffective. The infected cow’s immune system could still fight the infection, but the antibiotic would be of no help. Yet the same bacterium could be susceptible to other types of antibiotics with different active ingredients. In theory, then, increased antibiotic resistance in mastitis bacteria could indeed limit the ability to treat and prevent mastitis with antibiotics. It is difficult to tell whether antibiotics really are less effective than they What’s ahead for antibiotic use At the CBMRN, dairy producers like Doug Morrison are working closely with researchers to identify mastitis research priorities and needs. Researchers will be working on several projects related to antibiotic resistance over a five-year period that began April 2006. Their results will help them answer these questions: 1. How can producers quickly determine whether or not a case of mastitis should be treated? Research underway at the CBMRN is aimed at validating a protocol that uses an on-farm culture system to determine, in just over 24 hours, whether a clinical case of mastitis needs to be treated. 2.What quantity of antibiotics are Canadian dairy farms currently using, and is this antibiotic use related to susceptibility in mastitis bacteria? With the help of the National Cohort of Dairy Farms, the CBMRN will estimate the quantity of antibiotics used for various reasons, and determine whether farms with more antibiotic-susceptible mastitis cases use fewer antibiotics. 3.Does the treatment of clinical mastitis or dry cows cause bacteria to develop antibiotic resistance? Canada and the U.S. are conducting a joint study to determine whether bacteria present in cows’ intestines are more resistant to antibiotics following dry cow treatment than those in the intestines of cows that do not receive dry treatment. All Canadian dairy producers are participating financially in the research program and are involved at all decision-making levels of the CBMRN. To learn more or to share your ideas and comments, visit the CBMRN’s website www.mastitisnetwork.org or contact Julie Baillargeon at [email protected]. were 10 or 30 years ago. Methods used to measure antibiotic susceptibility have changed so much over the years results can’t be compared. A study conducted over two to three years comparing antibiotic susceptibility of mastitis bacteria in first-calf heifers and older cows after calving found no difference between the two groups. There is no scientific data to suggest clinical mastitis is less responsive to antibiotic treatment now than before. The theoretical principle behind the prevention of antibiotic resistance is to reduce the likelihood antibioticresistant bacteria could have a competitive advantage over antibioticsusceptible bacteria. In practice, this means using the right antibiotic for a long enough time and at a high enough dose to kill the bacteria. To ensure a treatment is both long enough and powerful enough, however, it’s recommended producers follow instructions on product labels or dosages prescribed by veterinarians. It is important never to reduce the treatment to shorten withdrawal time or limit treatment cost. When one of his cows contracts clinical mastitis, Doug always asks himself whether he should treat her. It’s a good question since research has clearly shown available antibiotics are ineffective against certain types of clinical mastitis. “It would be really useful to have a test that would quickly show us whether or not antibiotics should be used in a given situation,” Doug says. That test could arrive soon. CBMRN researchers are currently working on validating methods for on-farm mastitis bacteria identification (see The Milk Producer, July 2007). Not treating mastitis cases that are unlikely to respond to treatment would reduce unnecessary antibiotic use, unjustified withdrawal times and the risk of increasing antibiotic resistance. While waiting for the new tools, Doug is evaluating a number of strategies for rational antibiotic use in mastitis treatment. For clinical MilkPRODUCER | November 2007 | 35 mastitis, he uses a treatment protocol developed in collaboration with his veterinarian. Although he is comfortable with using antibiotics when necessary, Doug is aware of consumer concerns and risks associated with antibiotic resistance. He relies heavily on CBMRN research to answer his questions on antibiotic resistance and to develop strategies for rational antibiotic use. “For me, antibiotics are a management tool that has to be used properly but that we can’t get along without,” Doug says. Daniel Scholl is director of the CBMRN and professor at the faculty of veterinary medicine at the University of Montreal; Herman Barkema is CBMRN mastitis monitoring research team leader and professor at the University of Calgary, faculty of veterinary medicine; and Julie Baillargeon is agronomist and CBMRN transfer manager. Resistance 101 What is it? Antibiotic resistance is the ability of bacteria to grow and multiply in the presence of an antibiotic. Resistance develops in bacteria with genes enabling them to produce proteins that protect against the effects of the antibiotic molecule. Is it reversible? In theory, bacterial populations that have become resistant to a certain class of antibiotics can become susceptible to them again after a prolonged discontinuation of antibiotic use. How does resistance develop? 1. By selection pressure. Bacterial populations often contain some cells susceptible to a given antibiotic and others more or less resistant. If an antibiotic administered at a low dose kills susceptible cells but fails to kill moderately resistant bacteria, the surviving bacteria will remain in the mammary gland, free to multiply and become the dominant strain. The bacterial population would then become more resistant. 2. By gene transfer. A number of the bacterial genes associated with antibiotic resistance are carried by plasmids, small DNA molecules found in a variety of bacterial species. Plasmids can be transferred between bacterial cells. When plasmids containing antibiotic-resistant genes are transferred to other bacteria, the recipient bacteria acquire resistance to antibiotics. 3. By induction. Bacterial genes must be turned on or induced to express the proteins required for antibiotic resistance. Factors that induce antibiotic resistance are not well understood, and are the focus of several research projects, especially in human medicine. 36 | November 2007 | MilkPRODUCER