What is the recommended dose and indication for Plazomicin (plazomicin) in patients with complicated urinary tract infections (UTIs), including pyelonephritis, with impaired renal function (creatinine clearance)?

Plazomicin Dosing and Indication

Plazomicin is FDA-approved specifically for complicated urinary tract infections (cUTI), including pyelonephritis, in adults, with a standard dose of 15 mg/kg IV every 24 hours for 4-7 days in patients with normal renal function (CrCl ≥90 mL/min). 1

FDA-Approved Indication

• Plazomicin is indicated exclusively for complicated urinary tract infections (cUTI), including pyelonephritis in adult patients 1
• It is particularly valuable for carbapenem-resistant Enterobacterales (CRE) infections, as it remains stable against aminoglycoside-modifying enzymes that compromise traditional aminoglycosides 2
• The drug demonstrates activity against KPC and OXA-48 producing CRE, with variable activity against MBL-producing strains 2

Standard Dosing for Normal Renal Function

For patients with CrCl ≥90 mL/min:

• Dose: 15 mg/kg IV every 24 hours 1
• Duration: 4-7 days of IV therapy 1
• Total treatment duration: 7-10 days (IV plus optional oral step-down after 4-7 days) 1
• Maximum IV duration: 7 days 1

Dosing Adjustments for Renal Impairment

Dose reduction is mandatory for patients with renal impairment 1, 3:

CrCl 60-89 mL/min:

• 15 mg/kg every 24 hours 1

CrCl 30-59 mL/min (Moderate Impairment):

• 10 mg/kg every 24 hours 1
• Therapeutic drug monitoring (TDM) is required 1, 3

CrCl 15-29 mL/min (Severe Impairment):

• 10 mg/kg every 48 hours 1
• TDM is required 1, 3

CrCl <15 mL/min or Dialysis:

• Insufficient data to recommend dosing - plazomicin should not be used 1

Critical Therapeutic Drug Monitoring Requirements

For all patients with CrCl <90 mL/min, TDM is mandatory to prevent nephrotoxicity 1, 3:

• Target trough concentration: <3 mcg/mL 1, 3
• Timing of trough measurement: Within 30 minutes before the second dose 1
• Action if trough ≥3 mcg/mL: Extend dosing interval by 1.5-fold 1
  • q24h → q36h
  • q48h → q72h

Creatinine Clearance Calculation Considerations

Weight-based adjustments are essential for accurate dosing 1:

• Use total body weight (TBW) to estimate CrCl via Cockcroft-Gault formula 1
• If TBW exceeds ideal body weight (IBW) by ≥25%: Use IBW for CrCl calculation 1
• For dose calculation in obese patients (TBW >25% above IBW): Use adjusted body weight = IBW + 0.4 × (TBW - IBW) 1

Renal Function Monitoring

• Assess CrCl before initiating therapy 1
• Monitor CrCl daily during treatment 1
• Serum creatinine increases ≥0.5 mg/dL occurred in 7.0% of plazomicin-treated patients versus 4.0% with meropenem 4

Clinical Efficacy Data

• Plazomicin demonstrated non-inferiority to meropenem for cUTI treatment 4
• Composite cure rate at test-of-cure: 81.7% (plazomicin) vs 70.1% (meropenem) 4
• Superior microbiologic eradication against ESBL-producing Enterobacterales: 82.4% vs 75.0% 4
• Lower microbiologic recurrence at late follow-up: 3.7% vs 8.1% 4

Guideline Recommendations for CRE-UTI

Plazomicin receives a weak recommendation (2D) as a treatment option for CRE-associated complicated UTI 2:

• Recommended dose in guidelines: 15 mg/kg IV every 12 hours for CRE-UTI 2
• Treatment duration: 5-7 days 2
• This guideline dosing differs from FDA labeling (which specifies q24h dosing) 1

Common Pitfalls and Caveats

• Do not use plazomicin for infections outside the urinary tract - it is only FDA-approved for cUTI 1
• Never skip TDM in renally impaired patients - trough concentrations ≥3 mcg/mL significantly increase nephrotoxicity risk 3
• Avoid mixing with other drugs - plazomicin should not be co-infused through the same IV line 1
• Insufficient data for dialysis patients - alternative agents should be selected 1
• The CARE trial showed plazomicin-based regimens resulted in lower mortality (24% vs 50%) and less acute kidney injury (16.7% vs 50%) compared to colistin-based regimens for serious CRE infections, though this trial was stopped early 2

Administration Details

• Dilute in 0.9% sodium chloride or lactated Ringer's to 50 mL final volume 1
• Infuse over 30 minutes 1
• Diluted solution stable for 24 hours at room temperature or 7 days refrigerated 1