In VitroActivity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-ResistantEnterobacteriaceaeand Isolates Carrying Carbapenemase Genes
ABSTRACTPlazomicin and comparator agents were tested by using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 U.S. hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC50/MIC90, 0.5/2 μg/ml) inhibited 99.2% of 4,362Enterobacteriaceaeat ≤4 μg/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, by applying CLSI breakpoints. The activities of plazomicin were similar amongEnterobacteriaceaespecies, with MIC50values ranging from 0.25 to 1 μg/ml, with the exception ofProteus mirabilisand indole-positiveProteeaethat displayed MIC50values of 2 μg/ml. For 97 carbapenem-resistantEnterobacteriaceae(CRE), which included 87 isolates carryingblaKPC, 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 and 95.5% of the gentamicin-resistant isolates, 96.9 and 96.5% of the tobramycin-resistant isolates, and 64.3 and 90.0% of the amikacin-resistant isolates according to CLSI and EUCAST breakpoints, respectively. The activities of plazomicin againstPseudomonas aeruginosa(MIC50/MIC90, 4/16 μg/ml) andAcinetobacterspecies (MIC50/MIC90, 2/16 μg/ml) isolates were similar. Plazomicin was active against coagulase-negative staphylococci (MIC50/MIC90, 0.12/0.5 μg/ml) andStaphylococcus aureus(MIC50/MIC90, 0.5/0.5 μg/ml) but had limited activity againstEnterococcusspp. (MIC50/MIC90, 16/64 μg/ml) andStreptococcus pneumoniae(MIC50/MIC90, 32/64 μg/ml). Plazomicin activity against theEnterobacteriaceaetested, including CRE and isolates carryingblaKPCfrom U.S. hospitals, supports the development plan for plazomicin to treat serious infections caused by resistantEnterobacteriaceaein patients with limited treatment options.