What is the recommended dose adjustment of Plazomycin (generic name) in patients with Acute Kidney Injury (AKI)?

Plazomycin Dosing in Acute Kidney Injury

Critical Recommendation

Plazomycin dosing information specific to AKI is not available in the provided evidence, but based on KDIGO guidelines for aminoglycosides (the drug class to which plazomycin belongs), avoid dose-adjusted plazomycin in AKI unless no less nephrotoxic alternatives exist, and if used, employ single daily dosing with therapeutic drug monitoring after 48 hours. 1

Aminoglycoside Class Guidance for AKI

Primary Approach

• Avoid aminoglycosides entirely in AKI unless no suitable, less nephrotoxic therapeutic alternatives are available 1
• The nephrotoxic potential of aminoglycosides makes them particularly problematic in patients with existing kidney injury 1

If Aminoglycoside Use is Unavoidable

Dosing Strategy:

• Use single daily dosing rather than multiple-dose daily regimens in patients with normal baseline kidney function 1
• Recent evidence suggests full-dose β-lactams and single-dose aminoglycosides may be appropriate in the first 48 hours of infection-induced AKI 2

Monitoring Requirements:

• Monitor aminoglycoside drug levels when single-daily dosing is used for more than 48 hours 1
• For multiple daily dosing regimens, monitor drug levels when treatment exceeds 24 hours 1

AKI-Specific Dosing Considerations

The First 48-Hour Window

• Consider deferring renal dose adjustments for the first 48 hours of therapy in infection-induced AKI 2, 3
• In patients with Gram-negative bacteremia and AKI stage ≥2, time to recovery was similar regardless of aminoglycoside dosing (full, low, or none: 3 vs 4 vs 3 days, p=0.612) 2
• Approximately 57.2% of patients with AKI on admission had resolution by 48 hours 3

GFR-Based Adjustments

• Temporary discontinuation or dose adjustment of renally excreted drugs is recommended in patients with GFR <60 mL/min/1.73 m² who have serious intercurrent illness increasing AKI risk 1, 4
• When precision is required for drugs with narrow therapeutic ranges (like aminoglycosides), consider methods based on cystatin C or direct GFR measurement rather than creatinine-based estimates 1, 4

Critical Pitfalls to Avoid

Premature Dose Reduction

• Avoid reflexive dose reduction based solely on admission creatinine in infection-induced AKI 3
• Unnecessary dose reduction in the setting of resolving AKI may lead to subtherapeutic levels and reduced clinical response 3
• AKI causes complex pharmacokinetic changes beyond simple renal clearance, including altered protein binding, hepatic metabolism, and drug distribution 5

Monitoring Gaps

• Do not rely on creatinine-based estimates alone for therapeutic drug monitoring 1
• Measure actual drug levels to guide dosing, particularly after 48 hours of therapy 1

Alternative Routes When Possible

• Consider topical or local applications of aminoglycosides (respiratory aerosols, instilled antibiotic beads) rather than IV administration when feasible 1

Special Populations

Cirrhosis with AKI

• Patients with cirrhosis and AKI have altered pharmacokinetics and increased risk of hepatorenal syndrome requiring special attention 1, 4
• Withdraw all potentially nephrotoxic agents and assess volume status before determining antibiotic dosing 1

Severity-Based Approach

• Assess AKI severity using KDIGO staging before finalizing dosing strategy 2
• Recovery of renal function occurred in 105/106 surviving patients with AKI stage ≥2, suggesting the dynamic nature of infection-induced AKI 2