Global Distribution and Epidemiologic Associations of Escherichia coli Clonal Group A, 1998–2007

James R. Johnson

, Megan E. Menard, Tsai-Ling Lauderdale, Chris Kosmidis, David Gordon, Peter Collignon, Joel N. Maslow, Arjana Tambić Andrašević, and Michael A. Kuskowski

Author affiliations: Veterans Affairs Medical Center, Minneapolis, Minnesota, USA (J.R. Johnson, M.E. Menard, M.A. Kuskowski); University of Minnesota, Minneapolis (J.R. Johnson, M.A. Kuskowski); National Health Research Institutes, Zhunan, Taiwan (T.-L. Lauderdale); University of Athens Medical School, Athens, Greece (C. Kosmidis); Australian National University, Canberra, Australian Capital Territory, Australia (D. Gordon, P. Collignon); Canberra Hospital, Canberra (P. Collignon); Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA (J.N. Maslow); University of Pennsylvania, Philadelphia (J.N. Maslow); University Hospital for Infectious Diseases, Zagreb, Croatia (A. Tambić Andrašević)

Abstract

Escherichia coli clonal group A (CGA) was first reported in 2001 as an emerging multidrug-resistant extraintestinal pathogen. Because CGA has considerable implications for public health, we examined the trends of its global distribution, clinical associations, and temporal prevalence for the years 1998–2007. We characterized 2,210 E. coli extraintestinal clinical isolates from 32 centers on 6 continents by CGA status for comparison with trimethoprim/sulfamethoxazole (TMP/SMZ) phenotype, specimen type, inpatient/outpatient source, and adult/child host; we adjusted for clustering by center. CGA prevalence varied greatly by center and continent, was strongly associated with TMP/SMZ resistance but not with other epidemiologic variables, and exhibited no temporal prevalence trend. Our findings indicate that CGA is a prominent, primarily TMP/SMZ-resistant extraintestinal pathogen concentrated within the Western world, with considerable pathogenic versatility. The stable prevalence of CGA over time suggests full emergence by the late 1990s, followed by variable endemicity worldwide as an antimicrobial drug–resistant public health threat.

Extraintestinal infections caused by Escherichia coli are a substantial source of illness, death, and increased health care costs and have become increasingly challenging to manage because of the rising prevalence of resistance to first-line antimicrobial drugs (1). The resistance problem is now recognized as having a prominent clonal component attributable in large part to the emergence and dissemination of specific antimicrobial drug–resistant clonal groups of extraintestinal pathogenic E. coli (2–6).
One such emergent antimicrobial drug–resistant extraintestinal pathogenic E. coli clonal group is clonal group A (CGA) (2). Most traditionally recognized extraintestinal pathogenic E. coli clonal groups derive from E. coli phylogenetic group B2; however, CGA derives from phylogenetic group D (7), and, according to multilocus sequence typing (MLST), CGA corresponds with clonal complex 69 (8,9).
CGA first came to attention during the late 1990s as a prominent cause of trimethoprim/sulfamethoxazole (TMP/SMZ)–resistant urinary tract infections among otherwise healthy women across the United States (2,10). Isolates of CGA typically exhibit a fairly conserved virulence genotype that includes P fimbriae (with the F16 structural subunit variant), group 2 capsule (with the K52 capsular antigen), and the aerobactin and yersiniabactin siderophore systems. They also commonly exhibit resistance to multiple antimicrobial agents other than TMP/SMZ, including tetracycline, chloramphenicol, streptomycin, and spectinomycin, with the corresponding resistance genes carried either on a large conjugative plasmid (2) or within a genomic resistance module (11).
CGA has been recognized primarily as a cause of community-acquired cystitis and pyelonephritis in adult women mainly in the United States (2,10,12,13). It is largely unknown to what extent CGA might have broader pathogenic capabilities with respect to anatomic site of infection (urine vs. nonurine), site of acquisition (hospital vs. community), and host age (adult vs. child). Likewise, although a global survey of E. coli clinical isolates from 2001 found CGA was significantly associated with the United States (14), assessment of its distribution beyond the United States has been limited (5). Furthermore, no recent data are available regarding whether the overall prevalence of CGA is rising, stable, or waning, as can occur on a local level for CGA and other extraintestinal pathogenic E. coli clonal groups (3,13). Therefore, because of the major public health implications of CGA, we assessed the prevalence of this E. coli clonal group during 1998–2007 in multiple locales in the United States and internationally, paying specific attention to specimen type, inpatient versus outpatient status of host, and host age.