English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background Delafloxacin (DLX) is a broad-spectrum fluoroquinolone antibiotic under FDA review for the treatment of ABSSSI. Previous studies determined DLX bacterial stasis and 1-log10 bacterial reduction free AUC0-24 / MIC (fAUC0-24/MIC) targets for Escherichia coli (EC) and Pseudomonas aeruginosa (PA) in a mouse thigh infection model. The resulting PK/PD targets were used to predict DLX target attainment probabilities (TAP) in humans. Methods Monte Carlo simulations were used to estimate TAP with DLX 300 mg IV, q12hr. Human DLX plasma pharmacokinetics were determined in patients with ABSSSI in a Phase 3 clinical trial. Individual AUC values were analyzed and determined to be log-normally distributed. The parameters of the AUC distribution were used to simulate random values for fAUC24, which then were combined with random MIC values based on 2014–2015 US distributions of skin and soft tissue isolates of EC (n = 108) and PA (n = 40), to calculate PK/PD TAPs. Results DLX fAUC0-24/MIC targets for bacterial stasis and 1-log10 bacterial reduction for EC were 14.5 and 26.2, and for PA were 3.81 and 5.02, respectively. The Monte Carlo simulations for EC predicted TAPs of 98.7% for stasis at an MIC of 0.25 μg/mL, and 99.3% for 1-log10 bacterial reduction at an MIC of 0.12 μg/mL. The simulations for PA predicted TAPs of 97.3% for stasis and 86.5% for 1-log10 bacterial reduction at an MIC of 1 μg/mL. E. coli MIC (ug/mL) Target 0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 Stasis 100 100 100 100 100 97.8 50.4 2.0 1-Log Kill 100 100 100 100 99.3 60.4 5.8 0.0 P. aeruginosa MIC (ug/mL) Target 0.03 0.06 0.12 0.25 0.5 1 2 4 5 Stasis 100 100 100 100 100 97.3 45.9 1.7 0.5 1-Log Kill 100 100 100 100 100 86.5 17.8 0.3 0.1 Conclusion DLX 300 mg IV, q12hr, should achieve fAUC24/MIC ratios that are adequate to treat ABSSSI caused by most contemporary isolates of EC and PA. For EC, isolates with DLX MICs ≤0.25 μg/mL comprised 73% of all isolates. For PA, isolates with DLX MICs ≤1 μg/mL comprised 88% of all isolates. Similar results would be expected for TAP with oral DLX 450 mg, q12hr. Disclosures R. Hoover, Melinta Therapeutics: Consultant, Consulting fee; A. Marra, Melinta Therapeutics: Employee, Salary; E. Duffy, Melinta Therapeutics: Employee, Salary; S. K. Cammarata, Melinta Therapeutics: Employee, Salary

Human Target Attainment Probabilities for Delafloxacin against Escherichia coli and Pseudomonas aeruginosa