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Drugs

, Volume 79, Issue 3, pp 243–269 | Cite as

Plazomicin: A Novel Aminoglycoside for the Treatment of Resistant Gram-Negative Bacterial Infections

  • Khalid EljaalyEmail author
  • Aisha Alharbi
  • Samah Alshehri
  • Jessica K. Ortwine
  • Jason M. Pogue
Review Article

Abstract

Plazomicin is a novel semisynthetic parenteral aminoglycoside that inhibits bacterial protein synthesis. It was approved by the United States Food and Drug Administration for use in adults with complicated urinary tract infections (cUTI), including pyelonephritis. Plazomicin displays potent in vitro activity against Enterobacteriaceae, including both extended-spectrum β-lactamase-producing and carbapenem-resistant isolates. Plazomicin’s enhanced Enterobacteriaceae activity is due to its stability to commonly encountered aminoglycoside-modifying enzymes that compromise the activity of traditional aminoglycosides. Plazomicin resistance in Enterobacteriaceae is via modification of the ribosomal binding site due to expression of 16S rRNA methyltransferases. Plazomicin does not display improved activity over traditional aminoglycosides against other problematic resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter baumannii. Plazomicin has been assessed in two phase III randomized controlled trials. The EPIC trial compared plazomicin and meropenem for the management of cUTI. In this trial, plazomicin demonstrated superiority in composite cure (81.7% vs 70.1%; difference 11.6%; 95% confidence interval [CI] 2.7–25.7) at the test-of-cure visit, which was driven by enhanced sustained microbiological eradication. The CARE trial compared plazomicin-based and colistin-based combinations in patients with serious infections due to carbapenem-resistant Enterobacteriaceae (CRE). In this analysis, plazomicin-based combinations were associated with numerically decreased mortality or serious disease-related complications when compared with colistin-based combinations (23.5% vs 50%, respectively; 90% CI −0.7 to 51.2). Furthermore, plazomicin was also associated with a lower incidence of nephrotoxicity than colistin. However, small sample sizes limit the interpretation of the findings in the CARE trial. Plazomicin is a novel aminoglycoside that offers clinicians an additional option for the management of CRE infections, with superior activity compared with traditional aminoglycosides and potentially improved efficacy and decreased toxicity compared with colistin.

Notes

Compliance with Ethical Standards

Funding

No funding was received for the development of this manuscript.

Conflict of interest

Khalid Eljaaly has no conflict of interest. Aisha Alharbi has no conflict of interest. Samah Alshehri has no conflict of interest. Jessica Ortwine has no conflict of interest. Jason M. Pogue has served as a consultant for, on the Speakers Bureau of, and/or received grant support from Achaogen, Merck, Melinta, Allergan, Tetraphase, Shionogi, and Nabriva.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Clinical Pharmacy, College of PharmacyKing Abdulaziz UniversityJeddahSaudi Arabia
  2. 2.Pharmacy Practice and Science, College of PharmacyUniversity of ArizonaTucsonUSA
  3. 3.Department of Pharmacy ServicesParkland Health & Hospital SystemDallasUSA
  4. 4.University of Texas Southwestern Medical SchoolDallasUSA
  5. 5.Department of Pharmacy Services, Sinai-Grace Hospital, Detroit Medical CenterWayne State University of School of MedicineDetroitUSA

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