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.

Human health risk assessment of penicillin/aminopenicillin resistance in enterococci due to penicillin use in food animals.

Penicillin and ampicillin drugs are approved for use in food animals in the United States to treat, control, and prevent diseases, and penicillin is approved for use to improve growth rates in pigs and poultry. This article considers the possibility that such uses might increase the incidence of ampicillin-resistant Enterococcus faecium (AREF) of animal origin in human infections, leading to increased hospitalization and mortality due to reduced response to ampicillin or penicillin. We assess the risks from continued use of penicillin-based drugs in food animals in the United States, using several assumptions to overcome current scientific uncertainties and data gaps. Multiplying the total at-risk population of intensive care unit (ICU) patients by a series of estimated factors suggests that not more than 0.04 excess mortalities per year (under conservative assumptions) to 0.14 excess mortalities per year (under very conservative assumptions) might be prevented in the whole U.S. population if current use of penicillin drugs in food animals were discontinued and if this successfully reduced the prevalence of AREF infections among ICU patients. These calculations suggest that current penicillin usage in food animals in the United States presents very low (possibly zero) human health risks.

Inhibition of resistance plasmid transfer in Escherichia coli by ionophores, chlortetracycline, bacitracin, and ionophore/antimicrobial combinations.

Medicinal feed additives bacitracin, chlortetracycline (CTC), laidlomycin, lasalocid, and salinomycin inhibited the transfer of multiresistance-conferring plasmid pBR325 (Tet(r) Amp(r) Cp(r), 6.0 kb) into selected gram-negative strains with the use of an in vitro model. High concentrations of ampicillin-sensitive competence-pretreated Escherichia coli HB 101 cells were exposed to 10% (v/v) of 1:10 dimethyl sulfoxide/agent : water containing test mixtures for 0.5 hr prior to plasmid addition and transforming conditions. Transformation was inhibited for all antimicrobials and showed a positive association wich higher concentration. Additional testing of ionophore compounds separately and in combination with bacitracin, chlortetracycline, lincomycin, roxarsone, tylosin, and virginiamycin at representative feed concentrations demonstrated 80.6% to >99.9% inhibition (P < 0.001) of resistance transfer. Bacitracin alone inhibited transformation within the range of 50-500 ppm. No increase in resistance transfer was observed when poultry-derived and reference gram-negative isolates having low or no transformation efficiency were additionally tested. The results suggest that these compounds, at relevant concentrations used in animal feed, may interfere with cell envelope-associated DNA uptake channels or other transformation competence mechanisms. Through these mechanisms, ionophores and cell membrane-interactive feed agents such as CTC and bacitracin may act to inhibit resistance transfer mechanisms within poultry and livestock.