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Abstract Background Omadacycline is a novel aminomethylcycline that recently completed Phase 3 clinical trials for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP). This study evaluated the activity of omadacycline against a broad collection of recent (2016) clinical isolates with molecularly characterized tetracycline resistance mechanisms. Methods A total of 177 Gram-positive and -negative clinical isolates were identified as carrying acquired tetracycline resistance genes and were included in this study. Isolates were previously subjected to next-generation sequencing followed by screening of known tetracycline resistance mechanisms. Susceptibility testing and interpretation were performed according to CLSI methods. Results Omadacycline demonstrated MIC50 values of 0.06–0.12 µg/mL against Gram-positive isolates carrying tet genes. Similar MIC results (0.06–0.12 µg/mL) were obtained against Gram-positive organisms carrying tet(K), tet(L)/tet(M) or tet(M). Omadacycline (MIC50/90, 0.12/0.25 µg/mL) and tigecycline (MIC50/90, 0.06/0.25 µg/mL) showed similar MIC results when tested against Staphylococcus aureus carrying tet(K). While tetracycline was less active (0.0–78.6% susceptible) against Tet(K)-producing S. aureus, doxycycline (MIC50/90, 0.5/0.5 µg/mL; 100.0% susceptible) was active in vitro. Omadacycline (MIC90, 0.25–2 µg/mL) and tigecycline (MIC90, 0.12–1 µg/mL) showed potent MIC results against Gram-positive isolates carrying tet(L) and/or tet(M). Tetracycline and doxycycline had MIC90 values of ≥8 µg/mL. Omadacycline (MIC90 4–32 µg/mL) and tigecycline (MIC90 0.5–2 µg/mL) were active against Gram-negative isolates harboring tet(A), tet(B) or tet(D) or a combination of tet. Tetracycline (MIC50/90, >16/>16 µg/mL) and doxycycline (MIC50/90, >8/>8 µg/mL) had elevated MIC50 and MIC90 results against these isolates. Conclusion Results presented here indicate that omadacycline is not adversely affected by tet genes present in contemporary Gram-positive and -negative clinical isolates, a characteristic that differs from the legacy tetracycline agents. Disclosures R. E. Mendes, Paratek Pharmaceuticals: Research Contractor, Research support. M. Castanheira, Paratek Pharmaceuticals: Research Contractor, Research support. E. S. Armstrong, Paratek Pharmaceuticals: Employee, Salary. J. N. Steenbergen, Paratek Pharmaceuticals: Employee and Shareholder, Salary. R. K. Flamm, Paratek Pharmaceuticals: Research Contractor, Research support.

1377. Omadacycline In Vitro Activity Against a Molecularly Characterized Collection of Clinical Isolates with Known Tetracycline Resistance Mechanisms