title: Predictive diagnostics for Escherichia coli infections based on the clonal association of antimicrobial resistance and clinical outcome.
abstract: The ability to identify bacterial pathogens at the subspecies level in clinical diagnostics is currently limited. We investigated whether splitting Escherichia coli species into clonal groups (clonotypes) predicts antimicrobial susceptibility or clinical outcome. A total of 1,679 extraintestinal E. coli isolates (collected from 2010 to 2012) were collected from one German and 5 U.S. clinical microbiology laboratories. Clonotype identity was determined by fumC and fimH (CH) sequencing. The associations of clonotype with antimicrobial susceptibility and clinical variables were evaluated. CH typing divided the isolates into >200 CH clonotypes, with 93% of the isolates belonging to clonotypes with ≥ 2 isolates. Antimicrobial susceptibility varied substantially among clonotypes but was consistent across different locations. Clonotype-guided antimicrobial selection significantly reduced "drug-bug" mismatch compared to that which occurs with the use of conventional empirical therapy. With trimethoprim-sulfamethoxazole and fluoroquinolones, the drug-bug mismatch was predicted to decrease 62% and 78%, respectively. Recurrent or persistent urinary tract infection and clinical sepsis were significantly correlated with specific clonotypes, especially with CH40-30 (also known as H30), a recently described clonotype within sequence type 131 (ST131). We were able to clonotype directly from patient urine samples within 1 to 3 h of obtaining the specimen. In E. coli, subspecies-level identification by clonotyping can be used to significantly improve empirical predictions of antimicrobial susceptibility and clinical outcomes in a timely manner.
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Tchesnokova
authors.forename: Mariya
authors.initials: M
authors.lastname: Billig
authors.forename: Sujay
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Elena
authors.initials: E
authors.lastname: Linardopoulou
authors.forename: Pavel
authors.initials: P
authors.lastname: Aprikian
authors.forename: Pacita L
authors.initials: PL
authors.lastname: Roberts
authors.forename: Veronika
authors.initials: V
authors.lastname: Skrivankova
authors.forename: Brian
authors.initials: B
authors.lastname: Johnston
authors.forename: Alena
authors.initials: A
authors.lastname: Gileva
authors.forename: Irina
authors.initials: I
authors.lastname: Igusheva
authors.forename: Angus
authors.initials: A
authors.lastname: Toland
authors.forename: Kim
authors.initials: K
authors.lastname: Riddell
authors.forename: Peggy
authors.initials: P
authors.lastname: Rogers
authors.forename: Xuan
authors.initials: X
authors.lastname: Qin
authors.forename: Susan
authors.initials: S
authors.lastname: Butler-Wu
authors.forename: Brad T
authors.initials: BT
authors.lastname: Cookson
authors.forename: Ferric C
authors.initials: FC
authors.lastname: Fang
authors.forename: Barbara
authors.initials: B
authors.lastname: Kahl
authors.forename: Lance B
authors.initials: LB
authors.lastname: Price
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Weissman
authors.forename: Ajit
authors.initials: A
authors.lastname: Limaye
authors.forename: Delia
authors.initials: D
authors.lastname: Scholes
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Evgeni V
authors.initials: EV
authors.lastname: Sokurenko
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000145:classification* / Q000187:drug effects* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D005260:Female; D005858:Germany; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins