Plazomicin is approved by the U.S. Food and Drug Administration (FDA) for adults with complicated urinary tract infections, including pyelonephritis, caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Enterobacter cloacae, in patients who have limited or no alternative treatment options. Zemdri is an intravenous infusion, administered once daily.[6][7][8][9] The FDA declined approval for treating bloodstream infections due to lack of demonstrated effectiveness.[3] The lack of demonstrated effectiveness was not so much about the antibiotic itself being ineffective so much as the low enrollment rate for the study. Studies using mouse models however, showed a high survival rate.[10]
The drug was developed by the biotech company Achaogen. In 2012, the U.S. Food and Drug Administration granted fast track designation for the development and regulatory review of plazomicin.[15] The FDA approved plazomicin for adults with complicated UTIs and limited or no alternative treatment options in 2018.[6] Achaogen was unable to find a robust market for the drug, and declared bankruptcy a few months later.[16] As part of the bankruptcy process, the rights to plazomicin were sold to Cipla USA, who currently markets ZEMDRI.[17] There is no generic plazomicin currently available in the US market.[18]
Synthesis
It is derived from sisomicin by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'.[19][11] The latter makes it impervious to acetylation (deactivation) by Aminoglycoside Acetyltransferase 6'-N- Type Ib (AAC(6')-Ib), the most prevalent AAC enzyme.[20]
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^"Plazomicin". fda.gov. Antimicrobial Drugs Advisory Committee. 2 May 2018. Archived from the original on 27 December 2020.
^ abZhanel GG, Lawson CD, Zelenitsky S, Findlay B, Schweizer F, Adam H, et al. (April 2012). "Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin". Expert Review of Anti-Infective Therapy. 10 (4): 459–473. doi:10.1586/eri.12.25. PMID22512755. S2CID31496981.
^Clinical trial number NCT02486627 for "A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP) (EPIC)" at ClinicalTrials.gov