Activity of the First-in-class LpxC Inhibitor ACHN-975 and Comparators Tested against Gram-negative Organisms Including Isolates with Characterized Resistance Mechanisms

≤0.25 ≤0.25 ≤0.25 - 1 100.0 / 0.0 100.0 / 0.0 Piperacillin/tazobactam 64 >64 2 - >64 27.3 / 45.5 18.2 / 72.7 Piperacillin/tazobactam 1 2 ≤0.5 - 16 100.0 / 0.0 98.4 / 0.0 Imipenem 0.5 1 0.25 - 1 100.0 / 0.0 100.0 / 0.0 0.5 0.5 ≤0.25 - 2 100.0 / 0.0 91.7 / 0.0 Piperacillin/tazobactam 16 >64 2 - >64 53.3 / 33.3 53.3 / 46.7 Piperacillin/tazobactam 8 32 2 - >64 58.3 / 8.3 50.0 / 41.7 Imipenem 8 >16 0.5 - >16 36.7 / 63.3 36.7 / 50.0 Imipenem 0.25 0.5 ≤0.12 - 1 100.0 / 0.0 100.0 / 0.0 Levofloxacin • The activity of ACHN-975 was greater than all other agents tested (MIC 50/90 , 0.12/0.25 µg/mL) against wildtype P. aeruginosa strains and this compound displayed remarkable activity against MβL-producing P. aeruginosa inhibiting all strains at ≤1 µg/mL (MIC 50 , 0.5 µg/mL) and carbapenem-resistant MβL-negative P. aeruginosa (MIC 50/90 , 0.5/1 µg/mL).