What is the recommended dose of Plazomycin (generic name) as per Infectious Diseases Society of America (IDSA) guidelines?

Plazomicin Dosing for Complicated Urinary Tract Infections

The IDSA-endorsed dosing regimen for plazomicin is 15 mg/kg intravenously every 24 hours for 4-7 days in patients with normal renal function (CrCl ≥60 mL/min), with dose adjustments required for renal impairment. 1

Standard Dosing by Renal Function

Normal to Mild Renal Impairment (CrCl ≥60 mL/min)

• 15 mg/kg IV every 24 hours is the recommended dose for complicated urinary tract infections 1, 2, 3
• Treatment duration is typically 5-7 days for uncomplicated cUTI 1
• This regimen achieved 88% composite cure at day 5 and 81.7% at test-of-cure in the pivotal EPIC trial 3

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

• 10 mg/kg IV every 24 hours is recommended 2
• Therapeutic drug monitoring (TDM) is mandatory in this population 4

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

• 10 mg/kg IV every 48 hours is recommended 2
• TDM is essential to prevent nephrotoxicity 4

End-Stage Renal Disease

• Plazomicin is not recommended in patients requiring renal replacement therapy due to insufficient efficacy and safety data 2

Therapeutic Drug Monitoring Strategy

TDM should be implemented for all patients with any degree of renal impairment (CrCl <90 mL/min) to reduce nephrotoxicity risk while maintaining efficacy. 4

TDM Threshold and Timing

• Target trough concentration: <3 μg/mL 5, 4
• Measure trough concentration before the second or third dose 4
• If trough ≥3 μg/mL, extend dosing interval using the Hartford nomogram approach 5

Hartford Nomogram Application

• The Hartford nomogram can optimize plazomicin dosing intervals (q24h, q36h, or q48h) based on 10-hour post-dose concentrations 5
• This approach reduced the proportion of patients with troughs ≥3 μg/mL from 27-57% to 0% while maintaining therapeutic AUC (121-368 μg·h/mL) 5

Indication-Specific Considerations

Complicated Urinary Tract Infections

• Plazomicin demonstrated noninferiority to meropenem with 88% composite cure at day 5 3
• Superior microbiologic eradication against ESBL-producing Enterobacteriaceae (82.4% vs 75.0% for meropenem) 3
• Lower rates of microbiologic recurrence (3.7% vs 8.1%) and clinical relapse (1.6% vs 7.1%) compared to meropenem at late follow-up 3

Carbapenem-Resistant Enterobacteriaceae (CRE)

• 15 mg/kg IV every 24 hours for bloodstream infections caused by CRE 1
• Treatment duration: 7-14 days depending on source control and clinical response 1
• Plazomicin showed lower all-cause mortality (23.5%) compared to colistin (50%) in CRE infections 2

Combination Therapy

• Plazomicin demonstrates synergy with piperacillin/tazobactam and ceftazidime against MDR Enterobacteriaceae 6
• No antagonism observed with any tested combination 6
• Combination therapy may be considered for severe infections or those with high bacterial burden 6

Safety Monitoring

Nephrotoxicity Risk

• Increases in serum creatinine ≥0.5 mg/dL above baseline occurred in 7.0% of patients (vs 4.0% with meropenem) 3
• Risk increases with trough concentrations ≥3 μg/mL 4
• Monitor serum creatinine at baseline, then every 2-3 days during therapy 4

Dose Adjustment Algorithm

1. If serum creatinine increases ≥0.5 mg/dL above baseline: measure trough concentration 4
2. If trough ≥3 μg/mL: extend dosing interval to q36h or q48h based on CrCl 5
3. If trough remains ≥3 μg/mL despite interval extension: consider alternative therapy 4

Common Pitfalls to Avoid

• Do not use standard q24h dosing in patients with CrCl <60 mL/min without dose reduction, as this significantly increases nephrotoxicity risk 2, 4
• Do not skip TDM in renally impaired patients, as trough-based monitoring is the only validated method to prevent toxicity while maintaining efficacy 4
• Do not use plazomicin in patients on dialysis due to lack of efficacy and safety data 2
• Do not underdose based on actual body weight in obese patients, as plazomicin dosing is weight-based and underdosing may lead to treatment failure 3