1364. Efficacy of Omadacycline against Molecularly Characterized Gram-Positive and Gram-Negative Pathogens Causing Infections in the Phase 3 CABP and ABSSSI Clinical Trials
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
  • IDWeek-2018-OMC_clinical_trials_Final.pdf (582.1 kB)
  • Background: Omadacycline (OMC) is a once-daily agent with IV and oral formulations. One Phase 3 trial for community-acquired bacterial pneumonia (CABP; OPTIC) and two Phase 3 trials for acute bacterial skin and skin structure infections (ABSSSI; OASIS-1 and OASIS-2) were completed. OMC and comparator efficacies were examined for molecularly characterized baseline pathogens.

    Methods: Gram-positive (24) and -negative (17) isolates from the OPTIC (26), OASIS-1 (10) or OASIS-2 (5) trials were selected for characterization. Susceptibility testing and interpretation was performed by CLSI methods. Gram-positive isolates were selected based on tetracycline and/or macrolide, lincosamide, streptograminB (MLSB) phenotypes, and tetracycline-nonsusceptible (NS) gram-negative isolates were selected. Isolates were subjected to next-generation sequencing followed by screening for known tetracycline and/or MLSB genes. The efficacy endpoint was investigator’s assessment of clinical response at post therapy evaluation (PTE).

    Results: All S. aureus (8 isolates) exhibited a doxycycline-NS phenotype (MIC, 8–16 µg/mL) and OMC MIC values of 0.25–0.5 µg/mL. All S. aureus carried tet(M), except 1 isolate with tet(K), and 1 isolate with tet(M) and tet(L). All but 1 S. pneumoniae (16 isolates; OMC MIC, 0.03–0.06 µg/mL) carried MLSB genes, while tetracycline- and doxycycline-NS isolates (12) had tet(M). E. coli (8 isolates; OMC MIC, 0.5–2 µg/mL), E. cloacae (2 isolates; OMC MIC, 2 µg/mL), and K. pneumoniae (6 isolates; OMC MIC, 2–16 µg/mL) carried tetracycline efflux-pump genes, tet(A) and/or tet(B), tet(D), and tet(A), respectively. tet genes were not detected in 1 K. pneumoniae (OMC MIC, 8 µg/mL). Clinical success was noted in 37/41 (90.2%) patients. Two linezolid-treated patients with S. aureus (OMC MIC, 0.25 µg/mL) from OASIS-1 and 1 OMC-treated patient from OPTIC with E. coli (OMC MIC, 2 µg/mL) had indeterminate PTE responses. One OMC-treated patient from OPTIC with K. pneumoniae (OMC MIC, 8 µg/mL) was a clinical failure at PTE.

    Conclusion: This study expands on OMC efficacy data analysis among patients infected with tetracycline-NS pathogens. These results indicate that OMC in vivo efficacy is not affected by tetracycline and/or MLSB resistance mechanisms.

    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: Scientific Advisor , Speaker honorarium .

    See more of: Novel Agents
    See more of: Poster Abstract Session

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.