5 research outputs found
8-Azatetracyclines: Synthesis and Evaluation of a Novel Class of Tetracycline Antibacterial Agents
A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (<i>tet</i>(K)) and ribosomal protection (<i>tet</i>(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection
Results of propensity-score-based analyses of the effect of antibiotic regimen on secondary outcome incidence.
<p>Results of propensity-score-based analyses of the effect of antibiotic regimen on secondary outcome incidence.</p
Creation of cohort: Eligible surgeries and distribution by surgical prophylaxis regimen.
<p>BL, beta lactam; SSI, surgical site infection; V, vancomycin; VASQIP, Veterans Affairs Surgical Quality Improvement Program.</p
Variable distributions among all VASQIP-assessed surgeries.
<p>Variable distributions among all VASQIP-assessed surgeries.</p
Fluorocyclines. 2. Optimization of the C-9 Side-Chain for Antibacterial Activity and Oral Efficacy
Utilizing a fully synthetic route to tetracycline analogues,
the C-9 side-chain of the fluorocyclines was optimized for both antibacterial
activity and oral efficacy. Compounds were identified that overcome
both efflux (<i>tet</i>(K), <i>tet</i>(A)) and
ribosomal protection (<i>tet</i>(M)) tetracycline-resistance
mechanisms and are active against Gram-positive and Gram-negative
organisms. A murine systemic infection model was used as an oral efficacy
screen to rapidly identify compounds with oral bioavailability. Two
compounds were identified that exhibit both oral bioavailability in
rat and clinically relevant bacterial susceptibility profiles against
major respiratory pathogens. One compound demonstrated oral efficacy
in rodent lung infection models that was comparable to marketed antibacterial
agents