Omadacycline (OMC) is a novel aminomethylcycline antibiotic, available in once-daily intravenous and oral formulations, that has been studied in 1 phase 3 trial (OPTIC) for community-acquired bacterial pneumonia (CABP) and 2 phase 3 trials (OASIS-1 and OASIS-2) for acute bacterial skin and skin structure infections (ABSSSIs). Structural modifications at the C-7 and C-9 positions allow OMC to overcome the 2 main mechanisms of resistance to tetracyclines, efflux pumps and ribosomal protection. Forty-one clinical isolates (24 Gram-positive and 17 Gram-negative) were selected for characterization (26 from the OPTIC study, 10 from the OASIS-1 study, and 5 from the OASIS-2 study). Susceptibility testing and interpretation were performed by the Clinical & Laboratory Standards Institute methods. Gram-positive isolates were selected based on tetracycline and/or macrolide, lincosamide, streptogramin B MLSB phenotypes, and tetracycline nonsusceptible (NS) Gram-negative isolates were selected. The efficacy end point was the investigator’s assessment of clinical response at posttherapy evaluation (PTE).
- Staphylococcus 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 Streptococcus pneumoniae carried MLSB-associated genes, while tetracycline- and doxycycline-NS isolates (n-12) had tet(M)
- Escherichia coli (8 isolates; OMC MIC, 0.5-2 μg/mL), Enterobacter cloacae (2 isolates; OMC MIC, 2 μg/mL), and Klebsiella 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 case of K pneumoniae (OMC MIC, 8 μg/mL). A total of 3 E coli isolates belonged to the epidemic ST 131 lineage
- 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.
Clinical success was noted in 14/16 (87.5%) OMC-treated subjects in OPTIC and 5/5 (100%) OMC-treated subjects in the combined OASIS studies.
These results indicate that OMC’s in vivo efficacy is not affected by tetracycline and/or MLSB resistance mechanisms, and expands the data on the efficacy of OMC among patients with tetracycline-NS pathogens.
Source: Mendes RE, et al. IDWeek 2018. Abstract 1364.