Antimicrobial Drug Resistance in Escherichia coli from Humans and Food Animals, United States, 1950–2002

Daniel A. Tadesse, Shaohua Zhao, Emily Tong, Sherry Ayers, Aparna Singh, Mary J. Bartholomew, and Patrick F. McDermott

Author affiliations: Food and Drug Administration, Laurel, Maryland, USA (D.A. Tadesse, S. Zhao, E. Tong, S. Ayers, A. Singh, P.F. McDermott); Food and Drug Administration, Rockville, Maryland, USA (M.J. Bartholomew)

Abstract

We conducted a retrospective study of Escherichia coli isolates recovered from human and food animal samples during 1950–2002 to assess historical changes in antimicrobial drug resistance. A total of 1,729 E. coli isolates (983 from humans, 323 from cattle, 138 from chickens, and 285 from pigs) were tested for susceptibility to 15 antimicrobial drugs. A significant upward trend in resistance was observed for ampicillin (p<0.001), sulfonamide (p<0.001), and tetracycline (p<0.001). Animal strains showed increased resistance to 11/15 antimicrobial agents, including ampicillin (p<0.001), sulfonamide (p<0.01), and gentamicin (p<0.001). Multidrug resistance (≥3 antimicrobial drug classes) in E. coli increased from 7.2% during the 1950s to 63.6% during the 2000s. The most frequent co-resistant phenotype observed was to tetracycline and streptomycin (29.7%), followed by tetracycline and sulfonamide (29.0%). These data describe the evolution of resistance after introduction of new antimicrobial agents into clinical medicine and help explain the range of resistance in modern E. coli isolates.

Antimicrobial drugs have played an indispensable role in decreasing illness and death associated with infectious diseases in animals and humans. However, selective pressure exerted by antimicrobial drug use also has been the major driving force behind the emergence and spread of drug-resistance traits among pathogenic and commensal bacteria (1). In addition, resistance has developed after advent of every major class of antimicrobial drugs, varying in time from as short as 1 year (penicillin) to >10 years (vancomycin) (2,3).
Escherichia coli is usually a commensal bacterium of humans and animals. Pathogenic variants cause intestinal and extraintestinal infections, including gastroenteritis, urinary tract infection, meningitis, peritonitis, and septicemia (4,5). Therapeutic options vary depending on the type of infection. For example, for urinary tract infections, trimethoprim/sulfamethoxazole and fluoroquinolones are treatments of choice (6), whereas for Shiga toxin–producing E. coli infections, antimicrobial drug therapy is not recommended (7). E. coli is sometimes used as a sentinel for monitoring antimicrobial drug resistance in fecal bacteria because it is found more frequently in a wide range of hosts, acquires resistance easily (8), and is a reliable indicator of resistance in salmonellae (9).
Surveillance data show that resistance in E. coli is consistently highest for antimicrobial agents that have been in use the longest time in human and veterinary medicine (10). The past 2 decades have witnessed major increases in emergence and spread of multidrug-resistant bacteria and increasing resistance to newer compounds, such as fluoroquinolones and certain cephalosporins (3). For example, a study of the susceptibility of E. coli isolates recovered from hospitals during a 12-year period (1971–1982) showed no major change in resistance to any of the antimicrobial drugs tested (11). In contrast, a retrospective analysis of E. coli from urine specimens collected from patients during 1997–2007 showed an increasing resistance trend for ciprofloxacin, trimethoprim/sulfamethoxazole, and amoxicillin/clavulanic acid (12). Similarly a 30-year (1979–2009) follow-up study on E. coli in Sweden showed an increasing resistance trend for ampicillin, sulfonamide, trimethoprim, and gentamicin (13). Although studies of farms have shown an association of multidrug-resistant E. coli with chronic antimicrobial drug exposure (14,15), there are few data on temporal trends of antimicrobial drug resistance in food animal E. coli isolates, particularly those recovered before 1980. Recent data are available in several countries that established resistance monitoring programs during the mid-1990s.
In the United States, the National Antimicrobial Resistance Monitoring System (NARMS) was established in 1996 to prospectively monitor changes in antimicrobial drug susceptibilities of zoonotic foodborne bacteria, including E. coli from retail meats (chicken breast, pork chops, ground beef, ground turkey), and chickens at slaughter. During 2000–2008, NARMS laboratories tested 13,521 E. coli isolates from chickens to determine the MIC to antimicrobial drugs essential in human and veterinary medicine. The resistance trend in chickens observed during this period varied on the basis of the antimicrobial agents. For example, resistance during 2000–2008 decreased slightly for kanamycin (16.1% to 10.2%), streptomycin (77.5% to 54.6%), trimethoprim/sulfamethoxazole (17.2% to 9.1%), and tetracycline (68.4% to 47.4%). Cefoxitin resistance increased from 7.4% in 2000 to 15% in 2006, and ceftriaxone resistance increased from 6.3% to 13.5%. Ciprofloxacin resistance remained low (<1%) during this period.
To better understand the historical emergence of resistance since the advent of the antimicrobial drug age, which led to baseline data in the first year of NARMS testing, we assayed E. coli collections from human and animal sources obtained during 1950–2002 for antimicrobial drug susceptibility. This information, when coupled with secular surveillance data, will provide a broader picture of evolution of resistance and lay the groundwork for understanding genetic mechanisms of resistance development and dissemination.