Aminoglycoside Antibiotic Plazomicin Approved For the Treatment of Complicated UTI

 

 

The United States FDA has approved the aminoglycoside antibiotic plazomicin​​ (ZEMDRI™ by Achaogen) for the treatment of​​ complicated urinary tract infections​​ caused​​ E. coli,​​ Klebsiella, Proteus,​​ and​​ Enterobacter​​ species.

 

 

 

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~  ​​ ​​​​ Plazomicin (ZEMDRI™)  ​​ ​​​​ ~

Indications

Plazomicin​​ (Zemdri) has been approved for the treatment of​​ complicated urinary tract infections​​ (cUTI), including​​ pyelonephritis, caused by​​ Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and​​ Enterobacter cloacae. ​​ It is approved in patients with cUTI who are 18 years and older who have limited or no alternative treatment options. ​​ 

 

 

 

Mechanism

Plazomicin is an​​ antibacterial aminoglycoside. ​​ It inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.​​ ​​ It appears to have primarily​​ bactericidal​​ properties with demonstrated efficacy against clinical infections mediated by the​​ gram-negative facultative anaerobes​​ Escherichia coli,​​ Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae.

 

 

Administration and Dosing

The recommended dosing of plazomicin is​​ 15 mg/kg IV over 30 minutes​​ Q24h for 4-7 days. ​​ Therapeutic drug monitoring​​ and dose adjustment should be considered in patients with renal impairment.

 

 

 

Adverse Events

  • Nephrotoxicity (boxed warning, 3-4% in clinical trials)

  • Ototoxicity (boxed warning, up to 2% in clinical trials)

  • Neuromuscular Blockade (boxed warning)

  • Fetal​​ Toxicity (boxed warning)

  • Hypersensitivity (label warning)

  • C. Difficile-Associated Diarrhea (label warning)

  • GI Distress (1-5 % in clinical trials)

  • Hypertension/Hypotension (3% in clinical trials)

  • Headache (1 % in clinical trials)

 

 

Contraindications & DDI

  • Hypersensitivity to aminoglycosides

  • Pregnancy Category X (evidence of fetal harm in humans, risks outweigh benefits)

 

 

~  ​​ ​​​​ Evidence-Basis  ​​ ​​​​ ~

Plazomicin was approved based on the results of a​​ phase II and a phase III​​ clinical trial evaluating efficacy in treating cUTI (including pyelonephritis):

  • Trial 1:​​ Randomized, phase II, double-blind, comparator-controlled. ​​ 98 patients w/ cUTI received​​ plazomicin, 47 received​​ levofloxacin. ​​ 88% of patients in the plazomicin​​ group experienced microbiological eradication​​ vs.​​ 81%​​ in the levofloxacin group.

  • Trial 2, EPIC study:​​ Randomized, phase III,​​ comparator-controlled. 191 patients w/ cUTI in​​ plazomicin​​ arm, 197 in​​ meropenem​​ arm.​​ 87.4% of patients experienced microbiological eradication in plazomicin group​​ compared to​​ 72.1%​​ in the meropenem group when evaluated 2-3 weeks after intravenous antibiotic therapy.

 

 

 

~  ​​ ​​​​ What is Complicated UTI?  ​​ ​​​​ ~

Complicated urinary tract infection (cUTI) refers to a condition involving a urinary tract infection where​​ infection has progressed beyond the bladder. ​​ Presentations suggesting cUTI include simple UTI symptoms (pain, urgency, or burning​​ with urination,​​ changes in urine color or cloudiness) along with fever, pyelonephritis, and/or sepsis or bacteremia. Pyelonephritis is a​​ kidney infection​​ characterized by fever, flank pain, costovertebral angle tenderness and sometimes nausea and vomiting.

 

 

by​​ pharmacologyreview

 

 

 

 

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