Research Article: Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection

Date Published: March 28, 2017

Publisher: Public Library of Science

Author(s): Veronika Tchesnokova, Hovhannes Avagyan, Elena Rechkina, Diana Chan, Mariya Muradova, Helen Ghirmai Haile, Matthew Radey, Scott Weissman, Kim Riddell, Delia Scholes, James R. Johnson, Evgeni V. Sokurenko, Ulrich Nübel.


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.

Partial Text

The rising prevalence of antimicrobial resistance among bacterial pathogens is one of today’s greatest medical challenges [1–4]. Because conventional cultures can take days to determine a pathogen’s antimicrobial susceptibility profile, new approaches are needed urgently to guide empiric (pre-culture) selection of antimicrobial therapy.

In this prospective observational cohort study we assessed a prototypic clonal diagnostics method for guiding selection of empirical therapy for E. coli UTI. Our findings support three main conclusions. First, when the test is performed at the point of care (here, a busy metropolitan urgent care clinic), it can detect E. coli and determine clonal identity with high specificity and sensitivity within 25–35 min of urine specimen availability, which is an acceptable timeframe for empiric antibiotic prescription. Second, if empiric prescribing were guided by clonal antibiograms from a pre-existing reference database, the frequency of antibiotic/pathogen mismatch could be reduced considerably. Third, use of clonal diagnostics could promote antimicrobial stewardship by encouraging empiric use of preferred antibiotics (e.g., T/S) over less preferred antibiotics (e.g., FQs).




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