1377. Omadacycline In Vitro Activity against a Molecularly Characterized Collection of Clinical Isolates with Known Tetracycline Resistance Mechanisms
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
  • IDWeek-2018-omadacycline-tet-genes.pdf (1.1 MB)
  • 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.

    Rodrigo E. Mendes, Ph.D.1, Mariana Castanheira, PhD1, Eliana S Armstrong, PhD2, Judith N. Steenbergen, PhD3 and Robert K. Flamm, PhD1, (1)JMI Laboratories, Inc., North Liberty, IA, (2)Paratek Pharmaceuticals, King of Prussia, PA, (3)Paratek Pharmaceuticals, Inc., King of Prussia, PA


    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 .

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