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
Posters
  • 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

    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: Scientific Advisor , Speaker honorarium .

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