This new consensus document on the use of vancomycin in the treatment of MRSA is a MUST READ for anyone treating MRSA (which pretty much means anyone reading this post!). The document can be found on the Infectious Diseases Society of America (IDSA) website. The following address should directly access the document:
http://idsociety.org/WorkArea/showcontent.aspx?id=13052
The panel consisted of representatives from the IDSA, the American Society of Health-System Pharmacists and the Society of Infectious Diseases Pharmacists. They take an evidence based, detailed look at the pharmacokinetics, dosing recommendations and monitoring of vancomycin for the treatment of MRSA infection. Little of this information is specific for skin and skin structure infection or diabetic foot infection but there are a number of important issues that are addressed and do directly pertain. Each recommendation is graded for the level of evidence and the grade of recommendation. There is also an easy reference table summarizing the major points.
Of particular interest to readers of this blog is a statement, rather buried in the document that mentions how the penetration of vancomycin into tissues of patients with diabetes is significantly lower than those without diabetes. How this may affect the use vanco in our diabetic foot infection population is never explored. Also of importance is the formalized recognition that vanco peak levels are not contributory and should not be drawn. Only serum trough levels give important information that can lead to dosing modification. The trough should be drawn once the drug reaches steady state which is noted to be after the 4th dose. This would mean that the trough should be drawn before the 5th dose is given.
What concerns me the most, however, is the continued recommendation of increasing the target trough levels from <10 mg/L to between 15-20 mg/L. This would be accomplished by significantly increasing the drug’s dosing to 15-20 mg/kg (actual body weight) particularly if the isolate’s MIC is 1 or greater. I should note that the authors grade this as a low level IIIB recommendation. This concept of increasing the dose and the subsequent trough has been around since the recognition of “MIC creep” (read the book for a full explanation). In my opinion, it is based more on pharmacokinetics of the drug than on actual clinical data, as evidenced by the low level grading. The studies that I have reviewed, also reviewed by the panel, show that increasing the dose may prevent the development of further resistance BUT does not translate into increased clinical efficacy and probably increase nephrotoxicity! The panel recognizes this potential but criticizes the toxicity studies as having technical issues rendering the results as less reliable. The idea of increasing the dose, and even giving a significant loading dose (of up to 30 mg/kg), may be important in the treatment of blood stream infections and pneumonia but I am not clear on its utility in the treatment of lower extremity infections.
Follow this literature…it is fascinating stuff.
