MADELEINE KLEVEN , PROJECT ASSISTANT, FOOD SAFETY PROGRAM AT FOOD ANIMAL CONCERNS TRUST
FDA allows some medically important antibiotics to be used for the whole life of the animals receiving them. This creates an increased risk of antibiotic resistance which can harm human and animal health. In 2016, FDA proposed adding limits on how long an antibiotic could be used in food animals. FDA must move forward with this proposal and in doing so make sure that durations are short enough to lower the risk of resistance and other negative side effects. Evidence from human medicine shows that using antibiotics for shorter periods or durations usually works just as well and leads to less resistance and other side effects. Read further to learn more.
Overusing antibiotics contributes to the spread of antibiotic resistance which in turn increases the likelihood that these lifesaving drugs will be ineffective when needed. One way antibiotics are overused is using them for longer periods of time than necessary. The Food and Drug Administration (FDA) knows this and has long acknowledged that using medically important antibiotics in food animals for long or unlimited durations increases the risk of antibiotic resistance. As far back as the 1970s, FDA required specific safety studies on antibiotic resistance to support applications for antibiotics that were to be given in feeds for more than 14 days. In 2003, FDA issued Guidance for Industry #152 (GFI#152), which establishes a risk management approach to resistance for all antibiotic drugs used in food animals. The Guidance recommends, for example, that antibiotics found to have high or medium risk of an adverse human health effect related to resistance not be administered to a group of animals for more than 21 days (see Tables 7 and 8). In 2013, FDA issued Guidance for Industry #213, which calls for “explicitly defined duration of dosing” on new drug label indications because “giving antimicrobial drugs to food-producing animals at low levels for long periods of time and in large numbers of animals may contribute to antibiotic resistance.”
Yet, according to the FDA, some 32% of the products containing medically important drugs for use in feed or water have label indications without duration limits. This means a farm can legally feed these drugs for the whole life of an animal. In September 2016, FDA announced that the agency intends to take action to “establish appropriately targeted durations of use” for these drugs and requested comments on the drugs with unlimited durations. However, its formal request for comments includes examples of “acceptable” duration limits that are troubling. By indicating that durations of 112 days in chickens and up to 15 weeks in pigs may suffice, FDA’s request casts doubt on whether the agency intends to undertake meaningful change. Both examples are much longer than the 14 and 21 days in existing regulation and guidance, which were set to protect human health.
In order to reduce the risk to public health from antibiotic resistance that results from overly long durations, FDA SHOULD set duration limits for drug labels consistent with GFI#152. This means that for any veterinary drug that the agency has found to have a high or medium risk to human health, based on an FDA assessment under GFI #152 or one submitted to FDA by a drug sponsor, the maximum duration limit should be no more than 21 days. An even simpler solution would be to prohibit any “continuous use” (i.e., 14 days or more as defined in the Code of Federal Regulations see 21 CFR 558.3 (b)(3)) of a medically important antibiotic in feed or water. If a farmer wants to use a medically important antibiotic for longer, they should be required to go back to the veterinarian to reconsider the need for the antibiotic.
Though there are limited scientific studies designed to solely analyze the role of durations of use on antibiotic resistance development in food animals, there is a large body of evidence from human studies indicating that shorter courses of therapy are effective in reducing the risk of antibiotic resistance. Members of the Keep Antibiotics Working Coalition have recently completed a rapid review of the literature analyzing the role of antibiotic durations on resistance development, and we’ve found shorter therapies are not only effective in lowering antibiotic resistance and incidence of superinfections but in many instances antibiotic therapy costs as well. Shorter course treatment regimens for several diseases including pyelonephritis, intra-abdominal infection, COPD, sinusitis, and cellulitis are just as effective as longer courses of treatment, and are safer alternatives for patients. Shorter courses of therapeutic intervention are able to reduce selective pressure driving resistance and lower the risk of developing serious infections with superbugs.
In an animal setting, researchers found that the use of certain classes of antibiotics (macrolides and lincosamides) in long-acting injections as well as in-feed result in low concentrations of the active substance in the animal for long periods of time contributing to the risk of antibiotic resistance.
The use of any class of antibiotic agent in an animal or a human will inevitably lead to a selection pressure in favor of resistant subpopulations. This selection pressure is heavily influenced by antibiotic characteristics as well as the dose, treatment interval and duration of treatment. In order to mitigate resistance development, the length of time that antibiotics are given must be reduced to the shortest duration possible.
Efforts to minimize antibiotic use must be prioritized in both an agricultural and medicinal setting. If we are to preserve the effectiveness of antibiotics and minimize the public health hazard that antibiotic resistance poses, antibiotics must be used more judiciously in not only hospitals and doctor’s offices but on the farm as well. Shortening durations of use for medically important antibiotics to under twenty-one days is an essential part of judicious use. FDA, consistent with its public health mission can and must make this happen to ensure the lives of animals and humans are protected.
 See 21 CFR 558.15; https://www.fda.gov/ohrms/dockets/ac/02/slides/3816s2_01_Gilbert.ppt).
 Guidance for Industry #152 Table 7 ranks extent of use as high, medium, or low. In Table 7, any flock- or herd-wise use is considered high extent of use independent of time and any use in a select group of animals for more than 21 days is ranked as high extent of use. GFI #152 Table 8 describes potential risk management steps based on risk, with more restrictive steps recommended for drugs found to have a higher risk. Table 8 lists low extent of use for high-risk drugs and low or medium extent of use for medium-risk drugs. In either case, according to Table 7 any use over 21 days is considered high or medium, so if the tables are applied as written then a duration of over 21 days would not be considered appropriate for drugs that are found to have high or medium risk.