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

Abstract

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 (MIC 50/90 0.5/2 mg/L) inhibited 95.8% of Enterobacteriaceae at ≤2 mg/L, including carbapenem-resistant Enterobacteriaceae (MIC 50/90 0.25/128 mg/L). Plazomicin was more active compared with other aminoglycosides against isolates carrying bla KPC (MIC 50/90 0.25/2 mg/L), isolates carrying bla OXA-48-like (MIC 50/90 0.25/16 mg/L) and carbapenemase-negative isolates (MIC 50/90 0.25/1 mg/L). Approximately 60% of the isolates harbouring bla VIM and bla NDM-1 carried 16S 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 (MIC 50/90 4/8 mg/L) was similar to amikacin activity (MIC 50/90 2/16 mg/L). Plazomicin demonstrated activity against CoNS (MIC 50/90 0.12/0.25 mg/L) and Staphylococcus aureus (MIC 50/90 0.5/1 mg/L). Plazomicin activity was limited against Acinetobacter spp. (MIC 50/90 8/>128 mg/L), Enterococcus spp. (MIC 50/90 32/128 mg/L) and Streptococcus pneumoniae (MIC 50/90 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.