How do I perform therapeutic drug monitoring (TDM) for vancomycin in a patient with impaired renal function (dialysis patient)?

Vancomycin Therapeutic Drug Monitoring in Dialysis Patients

Loading Dose Strategy

Administer a full weight-based loading dose of 20-25 mg/kg (actual body weight) regardless of dialysis status, as the loading dose is not affected by renal function and is essential to rapidly achieve therapeutic concentrations. 1, 2

• The loading dose fills the volume of distribution, which remains unchanged in dialysis patients 3
• Even in anuric patients, give the full loading dose of at least 15 mg/kg 1
• For seriously ill patients with suspected MRSA infection, consider 25-30 mg/kg 3
• Infuse over at least 60 minutes for doses ≤1 g, or 90-120 minutes for larger doses to prevent red man syndrome 1

Timing of Administration

Give vancomycin during the last hour of the dialysis session to minimize removal and maintain therapeutic levels. 4

• Vancomycin is significantly removed during dialysis (35-43% reduction during SLED sessions) 5
• Administration during dialysis allows for immediate post-dialysis therapeutic levels 4
• High-flux membranes remove more vancomycin than low-flux membranes 4

Maintenance Dosing Algorithm

After the loading dose, administer maintenance doses post-dialysis based on the interdialytic interval:

• For 3x/week hemodialysis: Give 500-1000 mg after each dialysis session 2, 4
• For SLED or extended dialysis: Give 1000 mg (875-1125 mg) immediately after each SLED session 5
• The specific maintenance dose depends on actual body weight (aim for 15-20 mg/kg) 2

Critical Pitfall to Avoid

Fixed-dose regimens of 1 g every 5-7 days fail to achieve therapeutic levels in the majority of hemodialysis patients, particularly those using high-flux membranes 4. This approach results in subtherapeutic levels in 16-42% of patients 4.

Therapeutic Monitoring Protocol

Draw trough levels immediately before the next dialysis session (pre-dialysis) to guide dosing adjustments. 4

Target Trough Concentrations:

• For serious infections (bacteremia, endocarditis, osteomyelitis, pneumonia): 15-20 mg/L 3, 2
• For non-severe infections: 10-15 mg/L 3

Monitoring Schedule:

• Draw the first trough before the second dialysis session (approximately 48-72 hours after loading dose) 4
• Continue monitoring pre-dialysis troughs with each session until stable 2
• Post-dialysis levels are uniformly subtherapeutic and should not guide dosing 4

Dose Adjustment Based on Trough Levels

If pre-dialysis trough is <10 mg/L: Increase the post-dialysis maintenance dose by 250-500 mg 2

If pre-dialysis trough is 10-15 mg/L: Maintain current dose for non-severe infections; increase for serious infections 3

If pre-dialysis trough is 15-20 mg/L: Maintain current dose for serious infections 3

If pre-dialysis trough is >20 mg/L: Hold the next dose and recheck trough before subsequent dialysis; resume at reduced dose when <20 mg/L 6

Special Considerations for Dialysis Modality

High-Flux vs. Low-Flux Membranes:

• High-flux polyethersulfone membranes remove significantly more vancomycin 4
• Patients on high-flux dialysis require higher maintenance doses 4
• No patient using low-flux membranes showed subtherapeutic levels with 1 g dosing, versus 31.6% with high-flux 4

SLED-Specific Considerations:

• Vancomycin half-life during SLED is approximately 13.6 hours 5
• Minimal rebound occurs (9.8%) 4 hours post-SLED 5
• Redosing immediately after SLED is necessary to maintain therapeutic concentrations 5

Residual Renal Function

If the patient has residual urine output (>100 mL/day), consider the interdialytic interval and residual clearance when calculating maintenance doses. 2

• Patients with residual function may require supplemental dosing between dialysis sessions 2
• Monitor trough levels more frequently in patients with fluctuating residual function 1

Nephrotoxicity Monitoring

Monitor serum creatinine before each dialysis session, though nephrotoxicity risk is lower in dialysis patients already without renal function. 6

• Sustained trough concentrations >20 mg/L increase nephrotoxicity risk 6
• Concomitant nephrotoxic agents (aminoglycosides, piperacillin-tazobactam, NSAIDs) amplify risk 3

Alternative Therapy Considerations

If vancomycin MIC is ≥2 mg/L, switch to alternative agents (daptomycin, linezolid, or ceftaroline) as target AUC/MIC ratios are not achievable. 3, 6