What is the recommended dose of Plazomycin (generic name) for treating Urinary Tract Infections (UTIs)?

Plazomicin Dosing for Urinary Tract Infections

For complicated urinary tract infections (cUTI), plazomicin is dosed at 15 mg/kg IV once daily for 4-7 days in patients with normal renal function, with dose adjustments required for renal impairment. 1, 2, 3

Standard Dosing Regimen

• The FDA-approved dose is 15 mg/kg IV every 24 hours for 4-7 days in adults with cUTI who have limited or no alternative treatment options 3, 4
• The EPIC trial demonstrated noninferiority to meropenem using this once-daily dosing regimen, with composite cure rates of 88.0% at day 5 and 81.7% at test-of-cure visit 4
• Treatment duration of 7-10 days is appropriate for most cUTI cases, with optional oral step-down therapy after at least 4 days of intravenous therapy 4

Dose Adjustments for Renal Impairment

• Dose reduction is mandatory for patients with moderate or severe renal impairment to reduce nephrotoxicity risk 5, 3
• For patients with creatinine clearance 30-59 mL/min, reduced doses of 8-12 mg/kg every 24 hours have been used 6
• Extended dosing intervals (every 36 or 48 hours) may be appropriate based on renal function, with the Hartford nomogram showing utility in optimizing intervals 6
• Plazomicin is not recommended in patients with severe renal impairment or those receiving renal replacement therapy 3

Therapeutic Drug Monitoring

• Therapeutic drug monitoring (TDM) should be implemented for all cUTI patients with any degree of renal impairment (mild, moderate, or severe) 5
• Target trough concentration is <3 μg/mL to reduce nephrotoxicity risk while maintaining efficacy 5, 6
• Trough-based TDM is specifically recommended to prevent elevated concentrations associated with serum creatinine increases ≥0.5 mg/dL above baseline 6
• The target AUC range is 121-368 μg·h/mL based on the EPIC trial population 6

Clinical Context and Indications

• Plazomicin is specifically indicated for cUTI caused by carbapenem-resistant Enterobacteriaceae (CRE), though this represents a weak recommendation with very low quality evidence 7, 1
• It demonstrates activity against KPC and OXA-48 producing CRE, with variable activity against MBL-producing strains 7
• In the CARE trial for serious CRE infections, plazomicin-based regimens resulted in lower mortality (24% vs 50%) and lower acute kidney injury (16.7% vs 50%) compared to colistin-based regimens 7, 1, 2

Safety Monitoring

• Monitor serum creatinine levels throughout therapy, as increases ≥0.5 mg/dL occurred in 7.0% of patients in clinical trials 4
• Common adverse reactions include decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, and hypotension 3
• As with all aminoglycosides, plazomicin may cause neuromuscular blockade, ototoxicity, and fetal harm in pregnant women 3

Important Caveats

• Plazomicin is reserved for patients with limited or no alternative treatment options due to multidrug resistance 3
• The drug is stable against aminoglycoside-modifying enzymes that compromise traditional aminoglycosides, making it valuable for resistant organisms 7
• At test-of-cure, plazomicin showed higher microbiologic eradication rates than meropenem for ESBL-producing Enterobacteriaceae (82.4% vs 75.0%) and lower rates of microbiologic recurrence (3.7% vs 8.1%) 4