c Enterobacteriaceae-associated bla CTX-M genes have become globally widespread within the past 30 years. Among isolates from Washington State cattle, Escherichia coli strains carrying bla CTX-M (CTX-M E. coli strains) were absent from a set of 2008 isolates but present in a set of isolates from 2011. On 30 Washington State dairy farms sampled in 2012, CTX-M E. coli prevalence was significantly higher on eastern than on northwestern Washington farms, on farms with more than 3,000 adult cows, and on farms that recently received new animals. The addition of fresh bedding to calf hutches at least weekly and use of residual fly sprays were associated with lower prevalence of CTX-M E. coli. In Washington State, the occurrence of human pathogens carrying bla CTX-M genes preceded the emergence of bla CTX-M -associated E. coli in cattle, indicating that these resistance determinants and/or their bacterial hosts may have emerged in human populations prior to their dissemination to cattle populations. E mergence and dissemination of antibiotic resistance traits in Gram-negative bacteria can occur rapidly and across wide geographic distances (1). Bacterial strains carrying the bla CTX-M family of extended-spectrum -lactamase (ESBL) genes have spread globally in less than 30 years (2, 3). Unlike other families of ESBL genes which result from point mutations in preexisting, narrower-spectrum -lactamase genes (bla TEM-1 and bla SHV ) (4), bla CTX-M -lactamase genes originated from chromosomal genes of Kluyvera species (2). The earliest Escherichia coli plasmid-associated bla CTX-M was detected from laboratory dogs used in pharmaceutical research in Japan in 1986, followed by isolations from human patients in Munich, Germany (1989), Argentina (1989), France (1989), and Poland (1996) (2). In North America, bla CTX-Mbearing Escherichia coli strains (CTX-M E. coli strains) were detected in humans in Canada in 2000 (5) and in the United States between 2001 and 2002 (6). By 2007 in the United States, 80% of 15 geographically dispersed medical centers reported E. coli or Klebsiella pneumoniae infections with associated bla CTX-M genes (7). In Washington State, the earliest reported clinical human E. coli strain carrying bla CTX-M was isolated in 2001 in Seattle (6). Currently, CTX-M enzymes are considered the most prevalent ESBLs in isolates of E. coli, K. pneumoniae, and Proteus mirabilis associated with human infections globally (8).In the United States, dairy cattle-associated CTX-M E. coli strains were first reported by Wittum and others in Ohio in 2009 (9). This Ohio research group later reported CTX-M in Salmonella enterica isolates from equine, swine, and turkey sources from six different states (10) and from swine finishing barns in 5 states (11). In the current study, we first tested E. coli isolates from Washington State dairy cattle banked from several earlier research projects to determine the time window of CTX-M E. coli emergence in this region and host species. The results of this retrospective study indicated rece...