In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes

ABSTRACT

Plazomicin 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 4,362 Enterobacteriaceae at ≤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 among Enterobacteriaceae species, with MIC₅₀ values ranging from 0.25 to 1 μg/ml, with the exception of Proteus mirabilis and indole-positive Proteeae that displayed MIC₅₀ values of 2 μg/ml. For 97 carbapenem-resistant Enterobacteriaceae (CRE), which included 87 isolates carrying bla_KPC, 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 against Pseudomonas aeruginosa (MIC₅₀/MIC₉₀, 4/16 μg/ml) and Acinetobacter species (MIC₅₀/MIC₉₀, 2/16 μg/ml) isolates were similar. Plazomicin was active against coagulase-negative staphylococci (MIC₅₀/MIC₉₀, 0.12/0.5 μg/ml) and Staphylococcus aureus (MIC₅₀/MIC₉₀, 0.5/0.5 μg/ml) but had limited activity against Enterococcus spp. (MIC₅₀/MIC₉₀, 16/64 μg/ml) and Streptococcus pneumoniae (MIC₅₀/MIC₉₀, 32/64 μg/ml). Plazomicin activity against the Enterobacteriaceae tested, including CRE and isolates carrying bla_KPC from U.S. hospitals, supports the development plan for plazomicin to treat serious infections caused by resistant Enterobacteriaceae in patients with limited treatment options.