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 SPR859 (tebipenem) is the active form of the orally bioavailable prodrug SPR994. Tebipenem is an oral carbapenem with a broad-spectrum activity against Gram-positive and -negative bacteria. SPR994 is being developed as an oral option for the treatment of complicated urinary tract infections (cUTI). The goal of these studies was to characterize the PK-PD of tebipenem against a diverse panel of Enterobacteriaceae. Methods 24-hour dose-fractionation and dose-ranging studies were carried out utilizing the one-compartment in vitro infection model. Bacteria (1 × 106 CFU/mL) were exposed to tebipenem concentrations that mimicked human healthy volunteer free-drug plasma (f) concentration–time profiles following oral drug administration. For the dose-fractionation studies, 7 total daily dose levels (fAUC range, 0.11 to 19.0 mg hours/L) were fractionated in equal divided doses administered every 4, 8 or 12 hours (q4h, q8h and q12h, respectively). A single challenge isolate, E. coli ATCC 25922 (MIC = 0.015 mg/L), was evaluated in the dose-fractionation studies. In the dose-ranging studies, 13 Enterobacteriaceae clinical isolates (MIC values from 0.008 to 0.25 mg/L) were exposed to doses ranging from 4.69 to 1200 mg administered q8h (fAUC ranging from 0.14 to 37.2 mg hours/L). Relationships between change in log10 CFU from baseline at 24 h and each of fCmax:MIC ratio, f%T&gt;MIC, and fAUC:MIC ratio, with and without adjustment for dosing interval tau for the latter (fAUC:MIC ratio·1/τ), were fit using Hill-type models. Results Dose-fractionation study results demonstrated the activity of tebipenem to be time-dependent, with both f%T&gt;MIC and fAUC:MIC ratio·1/τ similarly describing the PK-PD of tebipenem. The relationship between change in log10 CFU from baseline at 24 hours and fAUC:MIC ratio·1/τ, as assessed using pooled data for 13 Enterobacteriaceae isolates evaluated in the dose-ranging studies, described the PK-PD of tebipenem well (Figure 1). The magnitude of fAUC:MIC ratio·1/τ associated with net bacterial stasis and 1- and 2-log10 CFU reductions from baseline was 7.23, 13.1, and 32.4, respectively. Conclusion These data will be useful to design other pre-clinical studies and support tebipenem dose selection for clinical studies in patients with cUTI. Disclosures All authors: No reported disclosures.

open forum infectious diseases

1565. Characterization of Tebipenem (SPR859) Pharmacokinetics–Pharmacodynamics (PK-PD) for Efficacy Against Enterobacteriaceae in a One-Compartment In Vitro Infection Model