In this analysis of ESBL-positive E. coli
isolates from across the United States (collected in 2000 to 2009), we defined the overall, by-center, and temporal prevalences of blaCTX-M-15
and ST131, identified associations of these two traits with one another and with virulence genotype and resistance profiles, and assessed the clonal structures of the populations. Our findings extend the results of a previous national survey (8
) and offer novel insights into the basis for the striking epidemiological success of both blaCTX-M-15
and E. coli
We found a marked predominance of both blaCTX-M-15
and ST131 among ESBL-producing E. coli
isolates collected across the United States and a very strong (albeit incomplete) association of these two traits with one another. This confirms, in a very different study population, the findings of a previous, smaller, single-year national survey (8
). Notably, both blaCTX-M-15
and ST131 occurred at each of the 15 participating centers, representing evidence of widespread distribution, but with by-center prevalence differences suggesting possible geographical or host-group specificity.
A novel finding in the present study was that both blaCTX-M-15
and ST131 appeared to have emerged and expanded in distribution during the past decade, since they were both significantly more prevalent from 2004 onward. Likewise, both occurred among isolates from children and adults alike. The somewhat lower overall prevalences of blaCTX-M-15
and ST131 in the present study (57% and 47%, respectively), compared with the previous national survey (78% and 67%, respectively) (8
), may reflect in part the present study's inclusion of “all-comer” and pediatric isolates from 2000 through 2009, compared with the previous survey's focus on blood isolates from adults from 2007.
Our findings provide insights into possible reasons for the striking epidemiological success of blaCTX-M-15 and ST131 and their association with one another. First, despite the obvious horizontal mobility of blaCTX-M-15 (as demonstrated by its occurrence in diverse phylogenetic backgrounds), blaCTX-M-15 showed evidence of clonal spread and expansion. That is, among the non-ST131 isolates, blaCTX-M-15 was concentrated within major phylogenetic groups A and D and within high-prevalence pulsotypes within those groups. Similarly, among ST131 isolates, blaCTX-M-15 was significantly associated with the highest-prevalence pulsotypes. To what degree blaCTX-M-15 has contributed directly to the expansion of these lineages, or is an opportunistic hitchhiker within intrinsically successful clones, warrants further study.
Second, blaCTX-M-15 was significantly associated with resistance to key first-line antimicrobials, notably β-lactams and fluoroquinolones, and (among non-ST131 isolates) with higher aggregate resistance scores. This predictably would favor expansion of blaCTX-M-15-containing strains in preference to other ESBL-producing E. coli strains in the presence of selection pressure from the corresponding antimicrobials, which is abundant and likely increasing.
Third, the large molecularly inferred virulence advantage of ST131 over non-ST131 isolates (regardless of blaCTX-M-15
status) and, within ST131, the similar (albeit smaller) advantage of blaCTX-M-15
-positive over blaCTX-M-15
-negative isolates would tend to favor expansion of ST131 and, specifically, its blaCTX-M-15
-positive subset. The marked inferred virulence advantage of ST131 strains may more than compensate for their modest resistance disadvantage compared with other ESBL-producing E. coli
strains. In this regard, the high prevalence of certain ST131 pulsotypes also may relate in part to differential virulence, since isolates from high-frequency pulsotypes were significantly more likely to qualify as ExPEC than were other ST131 isolates (92% versus 67%; P
= 0.0002). These highly successful lineages appear to represent an extreme version of the combined threats of virulence and resistance (22
Study limitations included the convenience sample (with its attendant potential biases), the undefined clinical background of the isolates, and a lack of information regarding the identity of the non-CTX-M-15 ESBLs and non-ST131 clonal groups. Strengths included the large sample size relative to other studies of ESBL-positive E. coli strains from the United States, long study interval, broad geographic range, inclusion of pediatric and adult isolates, and extensive molecular characterization of the isolates.
In summary, in this large molecular-epidemiological analysis of ESBL-producing E. coli clinical isolates from the United States (collected in 2000 to 2009), we found a predominance of blaCTX-M-15 and ST131 strains, which were widely dispersed geographically, involved pediatric as well as adult patients, and increased significantly in prevalence during the study period. Both entities were strongly associated with one another and, especially in combination, with enhanced molecularly inferred virulence, extensive antimicrobial resistance, and decreased clonal diversity, suggesting recent clonal expansion and dissemination. These findings confirm the importance in the United States of the ST131 clonal group and its characteristic blaCTX-M-15 gene, suggest possible reasons for their emergence, and underscore the need for effective predictive and preventive measures.