Plazomicin and comparators agents were tested using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 United States hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC50/90, 0.5/2 μg/ml) inhibited 99.2% of 4,362 Enterobacteriaceae at ≤4 μg/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, applying CLSI breakpoints. The activity of plazomicin was similar among Enterobacteriaceae species with MIC50 values ranging from 0.25 to 1 μg/ml, with exception of Proteus mirabilis and indole-positive Proteaee that displayed MIC50 values of 2 μg/ml. Against 97 carbapenem-resistant Enterobacteriaceae (CRE) that included 87 isolates carrying blaKPC, plazomicin inhibited all but 1 isolate at ≤2 μg/ml (99.0% and 98.9%, respectively). Amikacin and gentamicin inhibited 64.9% and 56.7% of the CRE isolates at the respective CLSI breakpoints. Plazomicin inhibited 96.5/95.5% of the gentamicin-resistant, 96.9/96.5% of the tobramycin-resistant and 64.3/90.0% of the amikacin-resistant isolates using CLSI/EUCAST breakpoints. The activity of plazomicin against Pseudomonas aeruginosa (MIC50/90, 4/16 μg/ml) and Acinetobacter spp. (MIC50/90, 2/16 μg/ml) isolates was similar. Plazomicin was active against coagulase-negative staphylococci (MIC50/90, 0.12/0.5 μg/ml) and Staphylococcus aureus (MIC50/90, 0.5/0.5 μg/ml), but had limited activity against Enterococcus spp. (MIC50/90, 16/64 μg/ml) and Streptococcus pneumoniae (MIC50/90, 32/64 μg/ml). Plazomicin activity against the Enterobacteriaceae tested, including CRE and isolates carrying blaKPC from U.S. hospitals, support the development plan for plazomicin to treat serious infections caused by resistant Enterobacteriaceae in patients with limited treatment options.
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