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.
~ Plazomicin (ZEMDRI™) ~
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.
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.
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.