Teaching an Old Class New Tricks: A Novel Semi-Synthetic Aminoglycoside, Plazomicin

Abstract

The emergence of multi-drug resistant (MDR) Gram-negative pathogens has become a serious worldwide health concern. Gram-negative bacteria such as Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli, Enterobacter spp.,) Acinetobacter spp., and Pseudomonas aeruginosa have rendered most antibiotics inactive, leaving aminoglycosides and polymyxins. Plazomicin (formerly ACHN-490), is a neoglycoside with unique structural modifications to the aminoglycoside pharmacophore that impart activity against many MDR Gram-negative organisms. ACHN-490 was recently approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections caused by MDR Enterobacteriaceae. In this era of increasing Gram-negative resistance, it is imperative to critically evaluate new antibiotics so that we understand how to use them optimally. The objective of this article is to discuss available data detailing plazomicin’s biochemistry, pharmacokinetic/pharmacodynamic characteristics, in-vitro activity and current progress in clinical trials. In addition, plazomicin’s potential role in therapy for the treatment of MDR Gram-negative infections will be discussed.