cefpodoxime and Skin-Diseases

Multidrug resistant Gram-negative bacterial infections are an increasing public health threat due to rapidly rising resistance toward β-lactam antibiotics. The hydrolytic enzymes called β-lactamases are responsible for a large proportion of the resistance phenotype. β-Lactamase inhibitors (BLIs) can be administered in combination with β-lactam antibiotics to negate the action of the β-lactamases, thereby restoring activity of the β-lactam. Newly developed BLIs offer some advantage over older BLIs in terms of enzymatic spectrum but are limited to the intravenous route of administration. Reported here is a novel, orally bioavailable diazabicyclooctane (DBO) β-lactamase inhibitor. This new DBO, ETX1317, contains an endocyclic carbon-carbon double bond and a fluoroacetate activating group and exhibits broad spectrum activity against class A, C, and D serine β-lactamases. The ester prodrug of ETX1317, ETX0282, is orally bioavailable and, in combination with cefpodoxime proxetil, is currently in development as an oral therapy for multidrug resistant and carbapenem-resistant

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; beta-Lactamases; Drug Design; Drug Evaluation, Preclinical; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Humans; Mice; Microbial Sensitivity Tests; Penicillin-Binding Proteins; Prodrugs; Protein Binding; Rats; Skin Diseases; Structure-Activity Relationship