Vancomycin Update - Extracted from DiPiro

DiPiro Joseph T, "Updated Guidelines for Vancomycin Dosing" (Update). Joseph T. DiPiro, Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey: Pharmacotherapy: A Pathophysiologic Approach, 7e: http://www.accesspharmacy.com.ezp.imu.edu.my/updatesContent.aspx?aid=4000077.

Vancomycin has been in continuous use since the 1950’s, primarily for treatment of methicillin-resistant staphylococcal infections. However, dosing recommendations continue to be refined. The Infectious Diseases Society of America along with the American Society of Health-System Pharmacists and the Society of Infectious Diseases Pharmacists published updated, evidence-based guidelines for vancomycin dosing with Staphylococcus aureus infections.¹ The purpose of optimal dosing is to maximize the therapeutic benefits while minimizing risks of toxicity.

Factors that influence vancomycin dosing include patient weight and renal function, as well as the susceptibility of the infecting organism and the severity of the infection. The primary pharmacodynamic measure of vancomycin efficacy is the area under the serum concentration–time curve divided by the minimal inhibitory concentration (MIC).

The guidelines recommend that vancomycin dosing should be based on serum trough levels obtained just before the fourth dose when steady-state concentrations have been reached. Subsequent doses should be determined by vancomycin levels and changes in renal function.

The recommended trough serum levels are 15-20 mg/L for complicated S. aureus infections (such as bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia) and at least 10 mg/L for less serious infections. Measurement of peak levels is not recommended. Trough levels less than 10 mg/L can result in development of vancomycin intermediately-susceptible S. aureus strains (VISA). The authors stated that there are limited data suggesting a direct causal relationship between toxicity and specific serum vancomycin concentrations.

Vancomycin is typically dosed at 15-20 mg/kg based on actual body weight (including for obese patients). For seriously ill patients a loading dose of 25-30 mg/kg can be given based on actual body weight. Subsequent doses are based on serum trough levels. Doses of 15-20 mg/kg (based on actual body weight) given every 8-12 hours are required in most patients with normal renal function, when the MIC is less than or equal to 1 mg/L. When the individual dose exceeds 1 g the infusion period should be extended to 1.5-2 hours.

Monitoring of serum trough vancomycin concentrations to reduce nephrotoxicity is recommended for patients receiving aggressive doses to achieve sustained trough levels of 15-20 mg/L and for patients at risk of nephrotoxicity (such as patients receiving concurrent treatment with nephrotoxins), as well as patients with unstable renal function and those receiving prolonged courses of therapy.

Frequent serum concentration monitoring for patients receiving short-course therapy (less than 5 days) or lower-intensity dosing (to achieve trough concentrations less than 15 mg/L) is not recommended. Once-weekly measurement of serum trough concentrations is recommended in patients receiving sustained dosing to achieve trough levels of 15-20 mg/L. Monitoring of trough levels to reduce ototoxicity is not recommended.

Readers are referred to the original article for more in-depth presentation of vancomycin serum concentration level monitoring.

Reference

1. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin therapeutic guidelines: A summary of consensus recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis. 2009;49:325-7. [PMID: 19569969]