Plazomicin: an intravenous aminoglycoside antibacterial for the treatment of complicated urinary tract infections

ABSTRACT

Introduction

Antimicrobial resistance continues to be a major public health concern due to the emergence and spread of multi-drug resistant (MDR) organisms, including extended spectrum ß-lactamase (ESBL) and carbapenemase producing Enterobacterales. Plazomicin is a novel aminoglycoside that demonstrates activity against MDR gram-negatives, including those producing ESBLs and most carbapenemases, and retains activity against aminoglycoside modifying enzymes as a result of structural modifications. The information discussed is meant to assist in identifying plazomicin’s place in therapy and to expand the clinician’s armamentarium.

Areas covered

Herein, we review the pharmacology, microbiology, clinical efficacy, and safety of plazomicin. To gather relevant information, a literature search was performed using PubMed, Ovid, and Google Scholar electronic databases. Search terms used include plazomicin, ACHN-490, extended spectrum ß-lactamase, ESBL, CRE, aminoglycoside modifying enzymes, and AME. Additional information was obtained from FDA review documents and research abstracts presented at international conferences.

Expert opinion

Plazomicin is a promising carbapenem or β-lactam/β-lactamase inhibitor-sparing alternative for the treatment of complicated urinary tract infections caused by MDR Enterobacterales. Although robust data for bloodstream infections and bacterial pneumonias are lacking, plazomicin may be considered in individual clinical scenarios if combination therapy is warranted provided supportive microbiological data and therapeutic drug monitoring are available.

KEYWORDS:

• Plazomicin
• ACHN-490
• aminoglycoside
• Enterobacterales
• carbapenem-resistant Enterobacterales
• extended-spectrum beta-lactamases
• carbapenemases
• aminoglycoside modifying enzymes
• urinary tract infection

Article highlights

• Antimicrobial resistance among gram-negative pathogens, specifically MDR Enterobacterales, is a major public health concern.

• There is an urgent need for carbapenem and ß-lactam/ß-lactamase inhibitor-sparing alternatives with increased activity against these MDR Enterobacterales.

• Plazomicin is a novel aminoglycoside with enhanced activity against ESBL-producing, carbapenemase-producing, and aminoglycoside-resistant Enterobacterales in comparison to newer ß-lactam/ß-lactamase inhibitors and older aminoglycosides.

• Plazomicin is approved for the treatment of cUTI/AP caused by E. coli, K. pneumoniae, P. mirabilis, and E. cloacae, in adults with limited or no alternative treatment options.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they were a former employee of and shareholder in Achaogen, the company that discovered, developed and launched plazomicin, and following the Achaogen bankruptcy, a paid consultant to Cipla, Inc. (the company that acquired the rights to plazomicin). The reviewer’s relationship with Achaogen ended in July 2019 and with Cipla in December 2019. Other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.