What adjustment is needed for vancomycin (Vancomycin) maintenance dosing at 750mg twice daily (BD) in a patient with impaired renal function, as indicated by a creatinine clearance of 41, and subtherapeutic trough levels of 7.7?

From the Guidelines

The vancomycin dosage should be increased to achieve a trough level within the therapeutic range of 15-20 mg/L, considering the patient's current trough level of 7.7 mg/L is below the recommended range. For most infections, vancomycin trough levels should be maintained between 10-15 mg/L, and for severe infections like endocarditis or osteomyelitis, between 15-20 mg/L 1. Consider increasing to 1000 mg twice daily, with continued monitoring of trough levels and renal function. The patient's creatinine clearance of 41 mL/min indicates moderate renal impairment but still allows for dosage adjustment. Trough levels should be measured just before the next dose (30 minutes prior) after steady state is reached (typically after 3-4 doses). The low current trough suggests suboptimal tissue penetration and potentially inadequate bacterial killing, which could lead to treatment failure or development of resistance. Regular monitoring of renal function is essential as vancomycin can be nephrotoxic, especially with higher doses or when combined with other nephrotoxic agents. Some key points to consider when adjusting the vancomycin dosage include:

• The patient's actual body weight and renal function should be taken into account when calculating the dosage 1
• The recommended dosage for patients with normal renal function is 15-20 mg/kg/dose every 8-12 hours, not to exceed 2 g per dose 1
• Individual pharmacokinetic adjustments and verification of achievement of target serum concentrations are recommended 1
• When individual doses exceed 1 g, the infusion period should be extended to 1.5-2 hours 1

From the FDA Drug Label

DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION (Adapted from Moellering et al. 1) Creatinine ClearancemL/minVancomycin Dosemg/24 h ... 40620 ...

The patient's creatinine clearance is 41 mL/min. According to the dosage table, the recommended vancomycin dose for a patient with this level of renal function is approximately 620 mg/24 hours.

• The patient is currently receiving 750 mg twice daily (1500 mg/24 hours), which is higher than the recommended dose.
• The trough level is 7.7, which is lower than the target trough level of 10-20 mg/L for most patients. To achieve the target trough level, the dose may need to be adjusted. Considering the patient's renal function and current dose, a dose reduction may not be necessary, but rather an adjustment to achieve the target trough level. However, the current dose is higher than recommended based on renal function alone. Dose adjustment should be made cautiously and with close monitoring of serum concentrations 2.

From the Research

Vancomycin Maintenance

• The patient's creatinine clearance is 41, and the trough levels are 7.7 at 750mg BD.
• According to the study 3, vancomycin dosing and monitoring practices associated with continuous infusion (CI) offer potentially greater reliability than intermittent infusion (II).
• The study 4 suggests that higher vancomycin trough concentrations (>20 mg/L) and intensive care unit (ICU) residence are independently associated with vancomycin-associated nephrotoxicity (VAN).
• The study 5 reveals that both trough level and area under the curve (AUC) are significant risk factors for the occurrence of vancomycin-induced nephrotoxicity.
• The study 6 demonstrates that initial trough levels of ≥20 mg/L are associated with early-onset VCM-associated nephrotoxicity in critically ill patients.
• The study 7 shows that pharmacy-led vancomycin dosing and monitoring can increase the percentage of patients achieving therapeutic trough levels and reduce nephrotoxicity.

Adjustment of Vancomycin Dose

• Considering the patient's trough levels are 7.7, which is below the therapeutic range of 10-20 µg/ml, an adjustment of the vancomycin dose may be necessary to achieve optimal trough levels.
• The equation (CrCl∙0·041) + 0·22, as mentioned in the study 3, can be used to estimate the patient's vancomycin clearance and adjust the dose accordingly.
• However, it is essential to monitor the patient's renal function and adjust the dose to minimize the risk of nephrotoxicity, as suggested by the studies 4, 5, and 6.

Monitoring and Dosing Strategy

• Regular monitoring of vancomycin trough levels and AUC is crucial to ensure optimal dosing and minimize the risk of nephrotoxicity, as recommended by the studies 3, 5, and 7.
• A pharmacy-led vancomycin dosing and monitoring protocol, as described in the study 7, may be beneficial in achieving therapeutic trough levels and reducing nephrotoxicity.