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

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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.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, College of Pharmacy, King Abdulaziz University, P.O. Box 80200, Jeddah, 21589, Saudi Arabia

    Khalid Eljaaly, Aisha Alharbi & Samah Alshehri

  2. Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA

    Khalid Eljaaly & Samah Alshehri

  3. Department of Pharmacy Services, Parkland Health & Hospital System, Dallas, TX, USA

    Jessica K. Ortwine

  4. University of Texas Southwestern Medical School, Dallas, TX, USA

    Jessica K. Ortwine

  5. Department of Pharmacy Services, Sinai-Grace Hospital, Detroit Medical Center, Wayne State University of School of Medicine, Detroit, MI, USA

    Jason M. Pogue

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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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Eljaaly, K., Alharbi, A., Alshehri, S. et al. Plazomicin: A Novel Aminoglycoside for the Treatment of Resistant Gram-Negative Bacterial Infections. Drugs 79, 243–269 (2019). https://doi.org/10.1007/s40265-019-1054-3

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