Location
Suwanee, GA
Start Date
17-4-2026 12:00 PM
End Date
17-4-2026 1:00 PM
Description
Vancomycin-resistant enterococci (VRE) are multidrug-resistant pathogens, associated with substantial morbidity and mortality having limited therapeutic options. Traditional tetracyclines are ineffective against VRE due to drug-resistance because of bacterial ribosomal protection proteins [tet(M)] and efflux pumps [tet(L)]. The reduced intracellular drug concentrations by tet(M) and tet(L) will prevent the inhibition of bacterial protein synthesis. Hence, tigecycline, a derivative of tetracycline was developed by introducing N,N-dimethylglycylamido group at C-9 position to overcome the tet(M) and tet(L) mediated drug-resistance while retaining the VRE anti-bacterial activity. However, the clinical use of tigecycline is limited to intravenous administration with possible gastrointestinal disturbance. To increase the oral bioavailability and anti-VRE potency, omadacycline, a novel derivative of tetracycline with 2,2-dimethylpropylaminomethyl at C-9 was developed, which also confers stability against both tet(M) and tet(L). Therefore, we have discussed the MOA, pharmacokinetics, and safety profile of FDA approved (2018) omadacycline. The 2,2-dimethylpropylaminomethyl bulky side chain reduces susceptibility to tetracycline-specific efflux pumps and enables sustained intracellular accumulation, thereby preserving anti-bacterial activity against strains resistant to earlier tetracyclines. Similar to tigecycline, omadacycline exhibits strong in-vitro activity against E. faecium and E. faecalis, including VRE isolates, with reported MIC₉₀ values of 0.12–0.25μg/mL. Additionally, omadacycline is approved for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) caused by gram positive (methicillin-susceptible and methicillin-resistant S. aureus, S. species, E. faecalis, E. cloacae), gram negative (H. influenzae, K. pneumoniae) and atypical pathogens (L. pneumophila, M. pneumoniae, C. pneumoniae) by. In summary, attributable to omadacyclines’ oral bioavailability and improved tolerability, it is a valuable therapeutic option for infections caused by multidrug-resistant gram-positive, negative and atypical bacterial pathogens.
Embargo Period
6-2-2026
Included in
Omadacycline vs other Tetracyclines: A novel drug against Vancomycin Resistant Enterococcus
Suwanee, GA
Vancomycin-resistant enterococci (VRE) are multidrug-resistant pathogens, associated with substantial morbidity and mortality having limited therapeutic options. Traditional tetracyclines are ineffective against VRE due to drug-resistance because of bacterial ribosomal protection proteins [tet(M)] and efflux pumps [tet(L)]. The reduced intracellular drug concentrations by tet(M) and tet(L) will prevent the inhibition of bacterial protein synthesis. Hence, tigecycline, a derivative of tetracycline was developed by introducing N,N-dimethylglycylamido group at C-9 position to overcome the tet(M) and tet(L) mediated drug-resistance while retaining the VRE anti-bacterial activity. However, the clinical use of tigecycline is limited to intravenous administration with possible gastrointestinal disturbance. To increase the oral bioavailability and anti-VRE potency, omadacycline, a novel derivative of tetracycline with 2,2-dimethylpropylaminomethyl at C-9 was developed, which also confers stability against both tet(M) and tet(L). Therefore, we have discussed the MOA, pharmacokinetics, and safety profile of FDA approved (2018) omadacycline. The 2,2-dimethylpropylaminomethyl bulky side chain reduces susceptibility to tetracycline-specific efflux pumps and enables sustained intracellular accumulation, thereby preserving anti-bacterial activity against strains resistant to earlier tetracyclines. Similar to tigecycline, omadacycline exhibits strong in-vitro activity against E. faecium and E. faecalis, including VRE isolates, with reported MIC₉₀ values of 0.12–0.25μg/mL. Additionally, omadacycline is approved for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) caused by gram positive (methicillin-susceptible and methicillin-resistant S. aureus, S. species, E. faecalis, E. cloacae), gram negative (H. influenzae, K. pneumoniae) and atypical pathogens (L. pneumophila, M. pneumoniae, C. pneumoniae) by. In summary, attributable to omadacyclines’ oral bioavailability and improved tolerability, it is a valuable therapeutic option for infections caused by multidrug-resistant gram-positive, negative and atypical bacterial pathogens.