Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection 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 10.1371/journal.pone.0174132 https://plos.figshare.com/articles/dataset/Bacterial_clonal_diagnostics_as_a_tool_for_evidence-based_empiric_antibiotic_selection/4794706 <div><p>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 <i>Escherichia coli</i>, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for <i>E</i>. <i>coli</i> clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect <i>E</i>. <i>coli</i> 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 <i>E</i>. <i>coli</i> 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 <i>E</i>. <i>coli</i> 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.</p></div> 2017-03-28 18:21:43 urine strain coli clonal-level antibiograms cohort study care patients resistance threshold Antibiotic selection empiric therapy clonotyping test clonal pathogen antimicrobial stewardship empiric antibiotic evidence-based empiric antibiotic selection coli UTI Urinary tract infections evidence-based medicine urine samples performance characteristics clonotype-specific antibiogram antibiotic use broad-spectrum agents clonal diagnostics approach Bacterial clonal diagnostics clonal diagnostics-guided antibiotic selection Escherichia coli coli clonotypes fluoroquinolone use antibiotic selection empiric antibiotic selection clonotype-specific antibiograms clonal distribution novel PCR-based clonotyping assay antibiotic resistance