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
Posters
  • 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

    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 .

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