Escherichia coli sequence type 131 (ST131) subclone H30 as an emergent multidrug-resistant pathogen among US veterans

Abstract

Background: Escherichia coli sequence type 131 (ST131), typically fluoroquinolone-resistant (FQ-R) and/or extended-spectrum β-lactamase (ESBL)-producing, has emerged globally. We assessed its prevalence and characteristics among US veterans.

Methods: In 2011, 595 de-identified E. coli clinical isolates were collected systematically within 3 resistance groups (FQ-susceptible [FQ-S], FQ-R, and ESBL-producing) from 24 nationally distributed Veterans Affairs Medical Centers (VAMCs). ST131 and its H30 subclone were detected by polymerase chain reaction and compared with other E. coli for molecular traits, source, and resistance profiles.

Results: ST131 accounted for 78% (184/236) of FQ-R and 64.2% (79/123) of ESBL-producing isolates, but only 7.2% (17/236) of FQ-S isolates (P < .001). The H30 subclone accounted for ≥95% of FQ-R and ESBL-producing, but only 12.5% of FQ-S, ST131 isolates (P < .001). By back-calculation, 28% of VAMC E. coli isolates nationally represented ST131. Overall, ST131 varied minimally in prevalence by specimen type, inpatient/outpatient source, or locale; was the most prevalent ST, followed distantly by ST95 and ST12 (13% each); and accounted for ≥40% (β-lactams), >50% (trimethoprim-sulfamethoxazole , multidrug), or >70% (ciprofloxacin, gentamicin) of total antimicrobial resistance. FQ-R and ESBL-producing ST131 isolates had higher virulence scores than corresponding non-ST131 isolates. ST131 pulsotypes overlapped extensively among VAMCs.

Conclusions: Among US veterans, ST131, primarily its H30 subclone, accounts for most antimicrobial-resistant E. coli and is the dominant E. coli strain overall. Possible contributors include multidrug resistance, extensive virulence gene content, and ongoing transmission. Focused attention to ST131, especially its H30 subclone, could reduce infection-related morbidity, mortality, and costs among veterans.

Keywords: Escherichia coli infections; ST131; antimicrobial resistance; extended-spectrum beta-lactamases; veterans.

Figure 1.

Distribution by resistance group of major Escherichia coli phylogenetic groups, ST131, and the fimH30 subclone among 595 E. coli isolates from veterans. Major phylogenetic groups: A (pink), B1 (yellow), B2 (blue), and D (green). ST131, fine cross-hatching; fimH30 subclone, bold cross-hatching. For prevalence of ST131 and the fimH30 ST131 subclone in the fluoroquinolone-susceptible group vs the fluoroquinolone-resistant or extended-spectrum β-lactamase group, P < .001. Abbreviations: ESBL, extended-spectrum β-lactamase; FQ-R, fluoroquinolone-resistant; FQ-S, fluoroquinolone-susceptible.

Figure 2.

Overall population prevalence of ST131 and other sequence types (STs) among Escherichia coli clinical isolates from veterans. The 19 most prevalent STs are shown. Estimated overall prevalence was calculated based on subsamples. Nearly all fluoroquinolone-resistant ST131 isolates represented the fimH30 ST131 subclone. Abbreviations: FQ-R, fluoroquinolone-resistant; FQ-S, fluoroquinolone-susceptible.

Figure 3.

Xbal pulsed-field gel electrophoresis–based dendrogram for 85 ST131 Escherichia coli isolates from veterans. The 85 isolates were selected randomly from the total ST131 population. Region denotes the 4 main US census regions. Horizontal lines bound the 5 most prevalent pulsotypes. Vertical line separates isolates with ≥98% overall profile similarity from less similar isolates. Abbreviations: ESBL, extended-spectrum β-lactamase; FQ, fluoroquinolone phenotype (R, resistant; S, susceptible); PFGE, pulsed-field gel electrophoresis.

Figure 4.

Virulence genotypes of 595 Escherichia coli isolates in relation to ST131 genotype, by antimicrobial resistance group. Traits shown are those (among 54 total) that yielded P < .05 for comparisons of ST131 (pink bars) vs non-ST131 (blue bars) isolates in at least 1 resistance group. Traits are arranged, from top to bottom, in order of descending prevalence among the fluoroquinolone-susceptible (FQ-S) ST131 isolates (if positively associated with ST131), then ascending prevalence among the FQ-S non-ST131 isolates (if negatively associated with ST131). P value symbols are shown adjacent to the higher-prevalence group when P < .05, and are as follows: *P < .05, **P < .01, ***P < .001. Rectangles enclose traits contributing to molecular definition of extraintestinal pathogenic E. coli. Trait definitions: afa/draBC, Dr-family adhesins; clbB and clbN, colibactin synthesis; cnf1, cytotoxic necrotizing factor; fimH, type 1 fimbriae; fyuA, yersiniabactin receptor; hlyA, α hemolysin; hra, heat-resistant agglutinin; iha, adhesin-siderophore; ireA, siderophore receptor; iroN, salmochelin receptor; iutA, aerobactin receptor; kpsM II, group 2 capsule; K1, K2, and K5, group 2 capsule variants; malX, pathogenicity island marker; ompT, outer membrane protease T; papA, papC, papEF, and papG, P fimbrial structural subunit, assembly, tip pilins, and adhesin, respectively; papG allele II, P adhesin variant; sat, secreted autotransporter toxin; sfa/foc, S or F1C fimbriae; traT, serum resistance-associated; usp, uropathogenic-specific protein; vat, vacuolating toxin. Abbreviations: ESBL, extended-spectrum β-lactamase; FQ-R, fluoroquinolone-resistant; FQ-S, fluoroquinolone-susceptible.

Figure 5.

Virulence and resistance scores among ST131 and non-ST131 Escherichia coli isolates within 3 resistance groups. Box-and-whisker plots show group medians (heavy horizontal bar), 25th and 75th percentiles (bottom and top of boxes, respectively), and maximum and minimum values (light horizontal bars). P values, as determined by the Mann-Whitney U test (2-tailed), are shown for ST131 vs non-ST131 comparisons when P < .05. A, Virulence scores (number of distinct virulence genes) among ST131 vs non-ST131 isolates within each resistance group. B, Resistance scores (number of resistance markers detected) among ST131 isolates vs non-ST131 isolates within each resistance group. Abbreviations: ESBL, extended-spectrum β-lactamase; FQ-R, fluoroquinolone-resistant; FQ-S, fluoroquinolone-susceptible.

Figure 6.

Antimicrobial resistance prevalence among 595 E. coli isolates according to ST131 status and resistance group. P value symbols (from the Mann-Whitney U test) for comparison of ST131 (pink bars) vs non-ST131 (blue bars) isolates within each resistance group, which are shown next to the higher prevalence group if P < .05, are as follows: *P < .05, **P ≤ .01, ***P ≤ .001. Abbreviations: AMP, ampicillin; A/S, ampicillin-sulbactam; CIP, ciprofloxacin; CTR, ceftriaxone; CZ, cefazolin; ESBL, extended-spectrum β-lactamase; FQ-R, fluoroquinolone-resistant; FQ-S, fluoroquinolone-susceptible; GEN, gentamicin; IMI, imipenem; MDR, multidrug resistance (to ≥3 or ≥5 drug classes); NIT, nitrofurantoin; T/S, trimethoprim-sulfamethoxazole.