Activity of plazomicin compared with other aminoglycosides against isolates from European and adjacent countries, including Enterobacteriaceae molecularly characterized for aminoglycoside-modifying enzymes an other resistance mechanisms

Background: Plazomicin is a next-generation aminoglycoside that was developed to overcome common aminoglycoside-resistance mechanisms. Objectives: We evaluated the activity of plazomicin and comparators against clinical isolates collected from 26 European and adjacent countries during 2014 and 2015 as part of the Antimicrobial Longitudinal Evaluation and Resistance Trends (ALERT) global surveillance programme. Methods: All 4680 isolates collected from 45 hospitals were tested for susceptibility to antimicrobials using the reference broth microdilution method. Selected isolates were screened for genes encoding carbapenemases, aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methyltransferases. Results: Plazomicin (MIC50/90 0.5/2 mg/L) inhibited 95.8% of Enterobacteriaceae at <= 2 mg/L, including carbapenem-resistant Enterobacteriaceae (MIC50/90 0.25/128 mg/L). Plazomicin was more active compared with other aminoglycosides against isolates carrying bla(KPC) (MICL50/90 0.25/2 mg/L), isolates carrying blooxA 48 Like (MIC50,,0 0.25/16 mg/L) and carbapenemase-negative isolates (MIC50/90 025/1 mg/L). Approximately 60% of the isolates harbouring bla(VIM) and bla(NDM-1) carried 165 rRNA methyltransferases (mainly rmtB and armA). AME genes were detected among 728 isolates and 99.0% of these were inhibited by plazomicin at <= 2 mg/L. Plazomicin activity against Pseudomonas aeruginosa (MICL50/90 4/8 mg/L) was similar to amikacin activity (MIC50/90 2/16 mg/L). Plazomicin demonstrated activity against CoNS (MIC50/90 0.12/0.25 mg/L) and Staphylococcus aureus (MIC50/90 5/1 mg/L). Plazomicin activity was limited against Acinetobacter spp. (MIC50/90 8/>128 mg/L), Enterococcus spp. (MIC50/90 32/128 mg/L) and Streptococcus pneumoniae (MIC50/90 32/64 mg/L). Conclusions: Plazomicin demonstrated activity against Enterobacteriaceae isolates tested in this study, including isolates carrying AMEs and a high percentage of the carbapenem-non-susceptible isolates. Plazomicin displayed activity against staphylococci.