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.

Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections

“…Antimicrobial resistance in Gram-negative pathogens has now reached a critical point, and many infections are no longer easily treated with carbapenems, the previous drugs of choice [1, 2]. Fortunately, several novel antibiotics targeted to 1 or more resistant determinants have recently been added to our armamentarium and others are in the pipeline [7, 22–24]. The introduction of these new agents, together with advances in rapid diagnostic techniques and progress in our understanding of pharmacokinetic/pharmacodynamic antibiotic optimization, have changed the landscape of treatment of MDR infections.…”

Cefiderocol: A Novel Siderophore Cephalosporin against Multidrug‐Resistant Gram‐Negative Pathogens

“…In an effort to further overcome Gram-negative resistance in carbapenem-resistant Enterobacteriaceae (CRE), plazomicin, a novel aminoglycoside, was developed. 14 Nonetheless, these antimicrobials have limited-to-no reliable activity against carbapenem-resistant A. baumannii. The creation of new agents with advanced spectra of activity, are required to successfully address the ever-evolving antimicrobial resistance achieved by Gram-negative pathogens.…”

“…The creation of new agents with advanced spectra of activity, are required to successfully address the ever-evolving antimicrobial resistance achieved by Gram-negative pathogens. 14,15 Cefiderocol (CFDC) is a novel siderophore cephalosporin conjugated with a catechol moiety, allowing for the chelation of ferric iron at the three-position. 16 Iron is a vital nutrient required for organism viability; therefore, this unique mechanism allows for CFDC to evade porin channel outer membrane modifications, beta-lactamases, and increased efflux pump expressions.…”

Evaluation of Eravacycline: A Novel Fluorocycline

“…Currently, some available agents used to treat these MDR infections have limitations in their efficacy, spectra of activity, and side effect profile . Fortunately, the past years have produced several agents in the pipeline with novel moieties and a potential to overcome these obstacles …”

“…6,7 Fortunately, the past years have produced several agents in the pipeline with novel moieties and a potential to overcome these obstacles. [8][9][10][11] Historically, tetracyclines (TET) have been used for the management of gram-negative skin and soft tissue and intraabdominal infections (IAI). 12 Although their use had been challenged with the onset of bacterial resistance, the development of new TET-like antibiotics, such as omadacycline and eravacycline (ERV), have the potential to overcome these challenges.…”