Plazomicin

Nature of the antibiotic

Class: Next-generation aminoglycoside (neoglycoside), semisynthetic (sisomicin based). It is not inactivated by most aminoglycoside-modifying enzymes (AME).
Molecular weight: 592.68.

It is synergistic with many antibiotics, including piperacillin-tazobactam.

Mechanism of resistance

Enterobacteriaceae: modification of the ribosomal binding site due to expression of 16S rRNA methyltransferases.

Adverse effect

• Ototoxicity – the animal study did not show ototoxicity. Few patients had mild vertigo and unilateral permanent tinnitus in phase II clinical trials [Riddle 2012].
• Nephrotoxicity – Phase II clinical trial showed a comparable increase in creatinine when compared to Levofloxacin. Two patients reported azotemia and mild renal insufficiency. [Riddle 2012].
• Cardiotoxicity – Statistically significant QT/QTc prolongation was seen in healthy volunteers but was deemed clinically insignificant.
• Mild-to-moderate headache, tinnitus, dizziness, and somnolence.

Spectrum

Gram-positive	Staphylococcus (MSSA, MRSA, and coag neg Staphylococcus). Streptococcus – not susceptible. Enterococcus – More effective on E faecium. E faecalis is usually resistant.
Gram-negative	Enterobacteriaceae – sensitive except NDM + organisms. Morganella, Proteus, Salmonella, Shigella are less sensitive. Non-fermenters- Usually have higher MIC (Pseudomonas, Acinetobacter), but it is more active than other aminoglycosides. Stenotrophomonas maltophilia is resistant.
Other organisms	It is active against Francisella, Yersinia and has some activity against Brucella.

Clinical trials

Phase III clinical trial ( EPIC trial) – compared plazomicin and meropenem for the management of cUTI. Plazomicin demonstrated superiority in composite cure at the test-of-cure visit (achieved enhanced sustained microbiological eradication).

Phase III clinical trial (CARE trial) – compared plazomicin-based and colistin-based combinations in patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Plazomicin-based combinations were associated with numerically decreased mortality, serious disease-related complications and incidence of nephrotoxicity.

Reference

Shaeer et al. Plazomicin: A Next‐Generation Aminoglycoside. Pharmacotherapy.
Volume39, Issue1, January 2019, Pages 77-93