title: Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.
abstract: Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients' urine within 25-35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ≥ 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care.
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA, United States of America.
authors.forename: Veronika
authors.initials: V
authors.lastname: Tchesnokova
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA, United States of America.|Kaiser Permanente Washington, Seattle, WA, United States of America.
authors.forename: Hovhannes
authors.initials: H
authors.lastname: Avagyan
authors.affiliation: Kaiser Permanente Washington, Seattle, WA, United States of America.|ID Genomics, Inc., Seattle, WA, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Rechkina
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA, United States of America.
authors.forename: Diana
authors.initials: D
authors.lastname: Chan
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA, United States of America.
authors.forename: Mariya
authors.initials: M
authors.lastname: Muradova
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA, United States of America.
authors.forename: Helen Ghirmai
authors.initials: HG
authors.lastname: Haile
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Radey
authors.affiliation: Children's Hospital, Seattle, WA, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Weissman
authors.affiliation: Kaiser Permanente Washington, Seattle, WA, United States of America.
authors.forename: Kim
authors.initials: K
authors.lastname: Riddell
authors.affiliation: Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States of America.
authors.forename: Delia
authors.initials: D
authors.lastname: Scholes
authors.affiliation: VA Medical Center and University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA, United States of America.|Kaiser Permanente Washington, Seattle, WA, United States of America.
authors.forename: Evgeni V
authors.identifier: http://orcid.org/0000-0003-2806-4121
authors.initials: EV
authors.lastname: Sokurenko
mesh_terms: D000900:Anti-Bacterial Agents / Q000145:classification / Q000494:pharmacology*; D015373:Bacterial Typing Techniques / Q000379:methods; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D004927:Escherichia coli Infections / Q000175:diagnosis* / Q000382:microbiology / Q000652:urine; D019317:Evidence-Based Medicine; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012680:Sensitivity and Specificity; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology; D014552:Urinary Tract Infections / Q000175:diagnosis* / Q000382:microbiology / Q000652:urine
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination