Longer-duration uses of tetracyclines and penicillins in U.S. food-producing animals: Indications and microbiologic effects

We review and analyze regulatory categories for longer duration of use (defined as ≥ 7 day) tetracyclines (TCs) and penicillins (PNs) approved for U.S. livestock and poultry, together with scientific studies, surveillance programs and risk assessments pertaining to antimicrobial resistance. Indications listed on a government database were grouped into three broad categories according to the terminology used to describe their use: disease control (C), treatment (T) and growth improvement (G). Consistent with mostly therapeutic uses, the majority (86%) of listed indications had C and/or T terms. Several studies showed interruption of early disease stages in animals and modulation of intestinal microflora. Longer-duration exposures are consistent with bacteriostatic modes of action, where adequate exposure time as well as concentration is needed for sufficient antimicrobial activity. Other effects identified included reduced animal pathogen prevalence, toxin formation, inflammation, environmental impacts, improved animal health, reproductive measures, nutrient utilization, and others. Several animal studies have shown a limited, dose-proportionate, selective increase in resistance prevalence among commensal animal bacteria following longer-duration exposures. Pathogen surveillance programs showed overall stable or declining resistance trends among sentinel bacteria. Quantitative, microbiologically detailed resistance risk assessments indicate small probabilities of human treatment failure due to resistance under current conditions. Evaluations of longer-duration uses of TCs, PNs, and other antimicrobial classes used in food-producing animals should consider mechanisms of activity, known individual- and population-level health and waste reduction effects in addition to resistance risks.