How to adjust vancomycin (Vancomycin) dose in a patient with a trough level of 29, which is above the target range of 15-20, while being treated for a severe wound infection with 1250mg (Vancomycin) every 8 hours?

Vancomycin Dose Adjustment for Supratherapeutic Trough Level

For a patient with a vancomycin trough level of 29 mg/L (target 15-20 mg/L), you should hold the next dose and resume at 1000 mg every 12 hours once the trough level decreases to <20 mg/L.

Assessment of Current Situation

The patient presents with:

• Severe wound infection requiring vancomycin therapy
• Current dosing: 1250 mg every 8 hours
• Target trough: 15-20 mg/L
• Measured trough before 4th dose: 29 mg/L (significantly above target range)

Immediate Management Steps

1. Hold the next scheduled dose of vancomycin

   • This is necessary since the trough level is substantially above the therapeutic range 1
   • Continuing with the current dosing regimen risks accumulation and increased toxicity

2. Recheck vancomycin trough level after 12-24 hours

   • This allows time for drug clearance while monitoring the decline in serum concentration

3. Monitor renal function

   • Check serum creatinine and calculate creatinine clearance
   • Vancomycin-induced nephrotoxicity is defined as multiple (≥2-3) consecutive increases in serum creatinine of 0.5 mg/dL or ≥50% increase from baseline 1

Dose Adjustment Algorithm

Once the trough level decreases to <20 mg/L:

1. Reduce both dose and frequency:

   • Decrease dose from 1250 mg to 1000 mg
   • Extend interval from q8h to q12h 1, 2

2. Calculate new maintenance dose based on patient's renal function:

   • If creatinine clearance can be measured, daily vancomycin dose (mg) should be approximately 15 times the glomerular filtration rate in mL/min 2

3. Recheck trough level before the 2nd or 3rd dose of the new regimen to ensure the target range of 15-20 mg/L is achieved 1

Monitoring Recommendations

• Subsequent trough monitoring: Measure trough levels before the 3rd or 4th dose of the new regimen to confirm therapeutic range
• Renal function: Monitor serum creatinine every 2-3 days while on vancomycin therapy
• Clinical response: Assess wound infection for signs of improvement or deterioration

Rationale for Approach

The IDSA guidelines recommend trough concentrations of 15-20 mg/L for severe infections such as wound infections to achieve an AUC/MIC ratio ≥400, which is the pharmacodynamic parameter most predictive of efficacy 1, 3. However, trough levels >20 mg/L are associated with increased risk of nephrotoxicity 4.

Recent evidence suggests that AUC-guided dosing rather than trough-only monitoring may reduce nephrotoxicity while maintaining efficacy 4, 5. If available, consider using Bayesian software to calculate AUC/MIC ratio, targeting 400-600 mg·h/L.

Common Pitfalls to Avoid

• Don't continue current dosing: Continuing the current regimen despite supratherapeutic levels increases toxicity risk
• Don't reduce dose without extending interval: Both parameters need adjustment to prevent reaccumulation
• Don't check levels too soon: Measuring levels before steady state is reached (typically 3-4 doses) may lead to inaccurate dose adjustments
• Don't forget to monitor renal function: Vancomycin can cause nephrotoxicity, especially with trough levels >20 mg/L

By following this approach, you can safely adjust the vancomycin dosing regimen to achieve therapeutic levels while minimizing the risk of toxicity in this patient with a severe wound infection.