Activity of Omadacycline When Tested Against Gram-positive Bacteria Isolated from Patients in the USA During 2015 as Part of a Global Surveillance Program.

Background: Omadacycline (OMC) is a broad spectrum aminomethylcycline in late stage clinical development for the treatment of acute bacterial skin and skin structure infections and community-acquired pneumonia that is being evaluated as both oral and intravenous, once-daily formulations.

Methods: A total of 5,102 Gram-positive (GP) organisms isolated during 2015 were selected from medical centers in the USA. Susceptibility testing (S) was performed by reference broth microdilution methods for OMC and comparators.

Results: OMC was active against Staphylococcus aureus (SA; MIC_50/90, 0.12/0.12 µg/ml). The MIC_50/90 for methicillin-resistant (MRSA) and MSSA isolates were identical at 0.12/0.12 µg/ml, respectively. All SA were S to tigecycline (TGC; MIC_50/90, 0.06/0.12 µg/ml), daptomycin (DAP; MIC_50/90, 0.25/0.5 µg/ml), linezolid (LZD; MIC_50/90, 1/1 µg/ml), and vancomycin (VAN; MIC_50/90, 0.5/1 µg/ml). S was lower in MRSA for levofloxacin (LEV; 29.6%), clindamycin (CLI; 71.2%), and erythromycin (ERY; 10.9/11.6%; CLSI/EUCAST). OMC (MIC_50/90, 0.12/0.5 µg/ml) and TGC (MIC_50/90, 0.06/0.12 µg/ml) were the most active agents tested against coagulase-negative staphylococci and against Enterococci (both agents MIC_50/90, 0.06/0.12 µg/ml). Against Streptococcus pneumoniae (SPN), the MIC₅₀ and MIC₉₀ for OMC (0.06/0.12 µg/ml) and TGC (0.03/0.06 µg/ml), were the lowest among the agents tested. OMC demonstrated activity against ceftriaxone (CRO) and LEV resistant isolates. OMC MIC values for SPN were 8-fold lower than CRO (MIC₉₀, 1 µg/ml) and LEV (MIC₉₀, 1 µg/ml). Against viridans group streptococci, OMC (MIC_50/90, 0.06/0.12 µg/ml) and TGC (MIC_50/90, 0.03/0.12 µg/ml; 100.0% S) were the most active agents tested. The MIC_50/90 for OMC against β-hemolytic streptococci was 0.06/0.12 µg/ml. All β-hemolytic streptococci were S to TGC, β-lactams, LZD, DAP, and VAN, however resistance to LEV (99.5/96.8% S [CLSI/EUCAST]), ERY (65.3% S), CLI (80.7% S) and tetracycline (54.5/54.3% S [CLSI/EUCAST]) occurred.

Conclusion: OMC was active against a broad range of GP bacteria including MRSA, SPN resistant to penicillin, CRO, and LEV; Enterococci, and streptococci. OMC warrants further study as therapy in infections where these organisms may occur.