1364. Efficacy of Omadacycline Against Molecularly Characterized Gram-Positive and Gram-Negative Pathogens Causing Infections in the Phase 3 CABP and ABSSSI Clinical Trials

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, streptogramin(B) (MLS(B)) 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 MLS(B) genes. The efficacy endpoint was investigator’s assessment of clinical response at post therapy evaluation (PTE). RESULTS: All S. aureus (eight 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 one isolate with tet(K), and one isolate with tet(M) and tet(L). All but one S. pneumoniae (16 isolates; OMC MIC, 0.03–0.06 µg/mL) carried MLS(B) genes, while tetracycline- and doxycycline-NS isolates (12) had tet(M). E. coli (eight isolates; OMC MIC, 0.5–2 µg/mL), E. cloacae (two isolates; OMC MIC, 2 µg/mL), and K. pneumoniae (six 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 one 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 one 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 MLS(B) resistance mechanisms. 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.