Objective: To review the mechanism of action, mechanisms of resistance, in vitro activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside.
Data sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.gov for published clinical data. References from selected studies were also used to find additional literature.
Study selection and data extraction: All English-language studies presenting original research (in vitro, in vivo, pharmacokinetic, and clinical) were evaluated.
Data synthesis: Plazomicin has in vitro activity against several multi-drug-resistant organisms, including carbapenem-resistant Enterobacteriaceae. It was Food and Drug Administration (FDA) approved to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis, following phase II and III trials compared with levofloxacin and meropenem, respectively. Despite the FDA Black Box Warning for aminoglycoside class effects (nephrotoxicity, ototoxicity, neuromuscular blockade, and pregnancy risk), it exhibited a favorable safety profile with the most common adverse effects being decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%) in the largest in-human trial.
Relevance to patient care and clinical practice: Plazomicin will likely be used in the treatment of multi-drug-resistant cUTIs or in combination to treat serious carbapenem-resistant Enterobacteriaceae infections.
Conclusions: Plazomicin appears poised to help fill the need for new agents to treat infections caused by multi-drug-resistant Enterobacteriaceae.
Keywords: aminoglycoside modifying enzymes (AME); aminoglycosides; carbapenem-resistant Enterobacteriales; extended-spectrum beta-lactamase; plazomicin.
© The Author(s), 2020.