Antibiotic use is known to promote the development of antibiotic resistance, but substantial controversy exists about the impact of agricultural antibiotic use (AAU) on the subsequent emergence of antibiotic-resistant bacteria among humans. AAU for animal growth promotion or for treatment or control of animal diseases generates reservoirs of antibiotic-resistant (AR) bacteria that contaminate animal food products. Mathematical models are an important tool for understanding the potential medical consequences of this increased exposure. We have developed a mathematical model to evaluate factors affecting the prevalence of human commensal AR bacteria that cause opportunistic infections (e.g., enterococci). Our analysis suggests that AAU hastens the appearance of AR bacteria in humans. Our model indicates that the greatest impact occurs very early in the emergence of resistance, when AR bacteria are rare, possibly below the detection limits of current surveillance methods.T he development of antibiotic resistance (AR) among pathogenic bacteria has emerged as a major public health concern. The appearance of AR has been directly linked with the use and overuse of antibiotics (1-4). It was reported that as much as 80% of total antibiotic production in the United States is used in agriculture, with a substantial portion of this used for the nontherapeutic purpose of growth promotion (4, 5). AR bacteria have been found in farm animals where antibiotics are heavily used (6-8), in associated food products (9, 10), in environments contaminated by animal waste (11,12), and in farm workers (13)(14)(15). Drugs that are used therapeutically in animals also may generate a reservoir of AR bacteria (16,17). AR bacteria in food animals threaten the efficacy of human drugs if AR bacteria or AR genes become incorporated into bacteria populations colonizing humans. To provide a basis for public policy discussions about agricultural antibiotic use (AAU), we have developed a mathematical model to quantify the medical consequences.AAU may cause AR bacterial infections in humans by two different processes. First, AAU increases the frequency of AR in zoonotic pathogens such as Campylobacter or Salmonella. These pathogens are typically acquired through exposure to contaminated animal food products. Human-to-human transmission of zoonotic pathogens is rare, although it may occur in settings where humans are immuno-compromised or where the gut community has been disturbed by heavy medical antibiotic use (MAU; ref. 18). Therefore, the incidence of AR in zoonotic infections of humans is directly related to the prevalence of AR bacteria in food animals. A risk-assessment model examining resistance in a zoonotic pathogen was recently proposed by FDA (see http:͞͞www.fda.gov͞cvm͞antimicrobial͞Risk asses.htm).Second, AR bacteria from food animals may facilitate the development of AR in human commensal bacteria which ordinarily colonize humans without causing infection. Commensal bacteria typically have long persistence times, frequent humanto-human ...