What is the dose of vancomycin (Vancomycin) for suspected sepsis?

From the Guidelines

For suspected sepsis, the recommended initial vancomycin dose for adults is 25-30 mg/kg actual body weight, administered as a loading dose intravenously, to rapidly achieve target trough concentrations and improve clinical outcomes. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of early and adequate antimicrobial dosing in critically ill patients with sepsis and septic shock 1. The use of a loading dose is particularly important in critically ill patients, as it helps to rapidly achieve therapeutic drug levels due to the expanded extracellular volume related to volume expansion following fluid resuscitation.

Some key considerations for vancomycin dosing in suspected sepsis include:

• Adjusting the dosing interval based on renal function, with 12-hour intervals for normal renal function and extended intervals for impaired renal function
• Targeting trough concentrations of 15-20 mg/dL for serious infections like sepsis
• Monitoring trough levels, typically drawn just before the fourth dose, and adjusting dosing accordingly
• Considering the use of antihistamines and prolonging infusion times to minimize the risk of red man syndrome and anaphylaxis associated with large doses of vancomycin 1
• Combining vancomycin with gram-negative coverage when used empirically for suspected sepsis, and reassessing treatment after 48-72 hours based on culture results and clinical response.

It is also important to note that vancomycin is used empirically for suspected sepsis when MRSA or resistant gram-positive organisms are potential pathogens, and that therapeutic drug monitoring is essential to ensure adequate drug levels and minimize the risk of nephrotoxicity and infusion-related reactions 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Infusion-related events are related to both the concentration and the rate of administration of vancomycin. Patients with Normal Renal Function Adults The usual daily intravenous dose is 2 g divided either as 500 mg every 6 hours or 1 g every 12 hours. Pediatric patients The usual intravenous dosage of vancomycin is 10 mg/kg per dose given every 6 hours. Neonates In pediatric patients up to the age of 1 month, the total daily intravenous dosage may be lower In neonates, an initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours for neonates in the 1st week of life and every 8 hours thereafter up to the age of 1 month. Patients with Impaired Renal Function and Elderly Patients Dosage adjustment must be made in patients with impaired renal function.

The dose of vancomycin for suspected sepsis is:

• Adults with normal renal function: 2 g per day, divided as 500 mg every 6 hours or 1 g every 12 hours 2
• Pediatric patients: 10 mg/kg per dose, given every 6 hours 2
• Neonates: initial dose of 15 mg/kg, followed by 10 mg/kg every 12 hours for the first week of life, and every 8 hours thereafter up to 1 month of age 2
• Patients with impaired renal function: dosage adjustment required, with initial dose of at least 15 mg/kg, and maintenance doses based on creatinine clearance 2

From the Research

Vancomycin Dosing for Suspected Sepsis

• The recommended vancomycin loading dose for suspected sepsis is 25-30 mg/kg, as suggested by therapeutic guidelines 3.
• A study found that high-dose initial vancomycin (>20 mg/kg) was associated with a significantly lower rate of nephrotoxicity compared to lower doses (≤20 mg/kg) 4.
• Another study found that a loading dose of 25 mg/kg followed by 15 mg/kg twice daily did not achieve the optimal trough concentration at steady state, but was associated with increased early clinical response 3.
• A pharmacokinetic study and Monte Carlo simulation suggested that a loading dose of 30 mg/kg, followed by a maintenance dose of 20 mg/kg every 6-12 hours, may be required to achieve the pharmacokinetic/pharmacodynamic target for treatment of MRSA septic shock 5.

Nephrotoxicity Risk

• The risk of nephrotoxicity is associated with higher vancomycin trough levels, with a cut-off of 15 mg/L detecting AKI with a sensitivity of 62.6% and a specificity of 65.5% 6.
• A study found that vancomycin use is associated with a higher risk of AKI when serum levels exceed 20 mg/L 7.
• The development of vancomycin-induced AKI is significantly associated with higher initial and maximum trough levels, with an exposure-response relationship indicating that increasing trough levels correlate with a significant rise of nephrotoxicity risk 6.

Dosage Recommendations

• The dosage of vancomycin for suspected sepsis should be individualized based on patient factors, such as renal function and weight 4, 3, 5.
• A loading dose of 25-30 mg/kg, followed by a maintenance dose of 15-20 mg/kg every 8-12 hours, may be a suitable regimen for patients with normal renal function 3.
• However, the optimal dosage regimen may vary depending on the specific patient population and the presence of renal impairment 7, 6.