What is the recommended dose of vancomycin for an adult with sepsis?

From the Guidelines

The recommended initial dose of vancomycin for an adult with sepsis is 25-30 mg/kg actual body weight administered intravenously as a loading dose, with subsequent dosing guided by therapeutic drug monitoring to achieve target trough concentrations of 15-20 μg/mL. This recommendation is based on the most recent and highest quality study available, which emphasizes the importance of optimizing vancomycin dosing in critically ill patients with sepsis to improve clinical outcomes 1.

Key Considerations

• The loading dose is essential to rapidly achieve therapeutic levels, especially in patients with sepsis who may have an expanded extracellular volume due to fluid resuscitation.
• Therapeutic drug monitoring is crucial to adjust dosing and ensure that target trough concentrations are achieved, with the first trough level typically drawn before the fourth dose.
• Dosing should be adjusted for patients with renal impairment, with creatinine clearance guiding modifications.
• Infusion should occur over at least 60-120 minutes to prevent "red man syndrome," a histamine-related reaction causing flushing and hypotension.
• Vancomycin is used for suspected or confirmed gram-positive infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), and the high dosing targets adequate tissue penetration and bactericidal activity while maintaining serum concentrations above the minimum inhibitory concentration (MIC) of the infecting organism.

Rationale

The Surviving Sepsis Campaign guidelines recommend optimizing antimicrobial dosing strategies in critically ill patients with sepsis and septic shock, including the use of loading doses for vancomycin to rapidly achieve therapeutic levels 1. The guidelines also emphasize the importance of therapeutic drug monitoring to adjust dosing and ensure that target trough concentrations are achieved.

Additional Guidance

• For patients with normal renal function, vancomycin dosages of 15-20 mg/kg (based on actual body weight) given every 8-12 hours may be required to achieve the suggested trough serum concentrations when the MIC is ≤1 mg/L 1.
• Alternative therapies should be considered if the vancomycin MIC is 2 mg/L for a patient with normal renal function, as a targeted AUC/MIC of 1400 may not be achievable with conventional dosing methods 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION ... 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.

• The recommended dose of vancomycin for an adult with sepsis is 2 g per day, which can be divided into 500 mg every 6 hours or 1 g every 12 hours 2.
• Each dose should be administered at no more than 10 mg/min or over a period of at least 60 minutes, whichever is longer.

From the Research

Vancomycin Dosing for Adults with Sepsis

• The recommended dose of vancomycin for an adult with sepsis is not explicitly stated in the provided studies, but several studies suggest the following:

Dosing Regimens

• A study from 1977 3 recommends a dose of 1 g every 12 hours for patients with normal renal function.
• A 2019 study 4 suggests that vancomycin doses of ≥ 2 g every 8 hours are required to consistently achieve key therapeutic targets in patients with a creatinine clearance of ≥ 80 mL/min/1.73 m2.
• Another study from 2008 5 recommends an initial dose of 3 grams of vancomycin per day to reach target concentrations above 20 mg/l.

Loading Doses

• A 2016 study 6 found that high single-dose vancomycin loading (> 20 mg/kg) is not associated with increased nephrotoxicity in emergency department sepsis patients.
• A 2019 study 7 also found that loading doses of vancomycin do not increase nephrotoxicity compared with lower doses in patients with severe renal dysfunction.

Considerations

• The dosing regimen should be adjusted based on the patient's renal function and other factors, such as weight and age.
• Therapeutic drug monitoring (TDM) of vancomycin is recommended to ensure optimal therapeutic exposure and minimize the risk of nephrotoxicity 5.