Therapeutic Drug Monitoring: Changes to Reference Ranges for Vancomycin, Gentamicin & Tobramycin

Therapeutic Drug Monitoring: Changes to Reference Ranges for Vancomycin, Gentamicin & Tobramycin

Vancomycin: New Trough reference range: 10-20 µg/mL; New Peak reference range: 30-50 µg/mL. Vancomycin is one of the most widely used antibiotics for the treatment of serious gram-positive infections involving methicillin-resistant S. aureus (MRSA), and has been in clinical use for nearly 50 years. Early in 2009 the Infectious Diseases Society of America, Society of Infectious Diseases Pharmacists, and American Society of Health-System Pharmacists published a consensus review of therapeutic monitoring of Vancomycin in adult patients (Ref: Am J Health-Sys Pharm 2009;66:82-98). Applying the principles of evidence-based medicine, they reviewed the scientific data and controversies associated with serum Vancomycin monitoring and provided recommendations based on available evidence. Here are some of their conclusions as they relate to therapeutic drug monitoring.

  1. Trough serum Vancomycin concentrations are recommended for monitoring its effectiveness. Trough concentrations should be obtained just before the next dose at steady-state conditions, the achievement of which is variable but occurs approximately after the fourth dose. A variety of pharmacokinetic/dynamic studies have supported the trough concentration as a practical and accurate surrogate for the preferred parameter of the ratio of the area under the serum drug concentration-vs.-time curve (AUC) and the minimum inhibitory concentration (MIC). An AUC/MIC ratio of ≥400 has been advocated as a target to achieve clinical effectiveness with Vancomycin.
  2. Based on evidence suggesting that S. aureus exposure to trough serum Vancomycin concentrations <10 µg/mL can produce strains with Vancomycin-intermediate S. aureus (VISA)-like characteristics, it is recommended that trough concentrations always be maintained above 10 µg/mL to avoid development of resistance.
  3. For severely ill patients and/or complicated infections caused by S. aureus such as bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia, trough serum Vancomycin concentrations of 15-20 µg/mL are recommended. These concentrations should achieve an AUC/MIC of ≥400 in most patients with MIC ≤1 µg/mL. If the Vancomycin MIC is ≥2 µg/mL in a patient with normal renal function, a targeted AUC/MIC of ≥400 is not achievable with conventional dosing methods. Thus, alternative therapies should be considered.
    [Note: Vancomycin MICs for MRSA at John Muir Health laboratories, including MuirLab, show the vast majority are 1-5-2.0 µg/mL. Data from August 2008 to the present show 0% inhibition at 0.25 & 0.50, 23% inhibition at 1.0, 99% inhibition at 2.0, & 100% inhibition at 4.0.]
  4. Although long considered a nephrotoxic and ototoxic agent, current formulations of Vancomycin have little potential for either adverse effect when used at conventional doses, unless it is used concomitantly with known nephrotoxic drugs (e.g. aminoglycosides) or at very high dosages. Thus available evidence does not support monitoring peak serum Vancomycin concentrations to decrease the frequency of nephrotoxicity or ototoxicity, as neither correlate with serum concentration.
  5. There are limited data suggesting a relationship between nephrotoxicity & trough serum Vancomycin concentration. Trough monitoring is best suited to patients receiving aggressive dosing targeted to produce sustained trough drug concentrations of 15-20 µg/mL, patients receiving concurrent nephrotoxins, patients with unstable renal function or are hemodynamically unstable, & those receiving prolonged courses of therapy.

Gentamicin and Tobramycin: Inclusion of mid-level drug concentration reference ranges for patients receiving once daily aminoglycoside dosing (based on dosage of 6 mg/Kg).

Dosing Interval
Time from dose q24hr q36hr ≥q48hr
10 hours <4.1 4.1-5.9 >5.9
11 hours <3.5 3.5-5.1 >5.1
12 hours <2.9 2.9-4.3 >4.3