Raising Concerns About the Vancomycin Dosing Recommendations In The IDSA MRSA Guidelines

For part three of this posting on the new Infectious Diseases Society of America (IDSA) methicillin resistant Staphylococcus aureus (MRSA) guidelines, I would like to comment on some of the executive summary points made about vancomycin dosing recommendations. I will use a similar format as before with posting the actual text and then adding my comments in italics.

I have kept the guideline’s evidence gradings in so you can determine for yourself whether you feel the recommendations are of a high enough level of medical evidence. I have also left the numbering intact so you can compare it to the original document found at https://cid.oxfordjournals.org/content/early/2011/01/04/cid.ciq146.abstr… ).

VIII. What are the recommendations for vancomycin dosing and monitoring?

These recommendations are based on a consensus statement of the American Society of Health-System Pharmacists, the IDSA and the Society of Infectious Diseases Pharmacists on guidelines for vancomycin dosing.3,4 You can read my earlier post to see what I think about those guidelines. Recommendations 60-63 drive me crazy. There is essentially NO good evidence to support bumping vancomycin dose/levels that high. The concept is based on a pharmacokinetic parameter called an AUC/MIC ratio.

I do not doubt this is a valid measure. What concerns me is that many pharmacists and infectious disease specialists have taken this to heart and are significantly increasing vancomycin doses and maintaining troughs of 15 to 20 µg/mL despite little evidence of increased efficacy and, in my humble opinion, good evidence of increased renal toxicity.

In fact, I personally know of a case of acute renal failure occurring in a diabetic foot infection. (No, I did not treat it.) This may be okay in bacteremia and pneumonia, but I am not at all comfortable with these recommendations in our patients with diabetes, who likely have preexisting renal problems. I will “split the difference.” I am okay with keeping the trough between 10 and 15 µg/mL. See recommendation 64.

60. IV vancomycin 15–20 mg/kg/dose (actual body weight) every 8–12 h, not to exceed 2 g per dose, is recommended in patients with normal renal function (B-III).

61. In seriously ill patients (e.g., those with sepsis, meningitis, pneumonia or infective endocarditis) with suspected MRSA infection, a loading dose of 25 to 30 mg/kg (actual body weight) may be considered. (Given the risk of red man syndrome and possible anaphylaxis associated with large doses of vancomycin, one should consider prolonging the infusion time to 2 h and use of an antihistamine prior to administration of the loading dose.) (C-III)

62. Trough vancomycin concentrations are the most accurate and practical method to guide vancomycin dosing (B-II). Serum trough concentrations should be obtained at steady state conditions, prior to the fourth or fifth dose. Monitoring of peak vancomycin concentrations is not recommended (B-II). Note the “fourth or fifth dose” recommendation. Do not rush to draw a level before that time as many do.

63. For serious infections, such as bacteremia, infective endocarditis, osteomyelitis, meningitis, pneumonia and severe SSTI (eg, necrotizing fasciitis) due to MRSA, vancomycin trough concentrations of 15–20 µg/mL are recommended (B-II). I do not know why “osteomyelitis” is frequently put in the same category as necrotizing fasciitis. There are so many varieties of osteomyelitis in so many locations. I can’t just classify it this way. I do not bump my vancomycin doses/levels for osteomyelitis just because it is osteomyelitis.

64. For most patients with SSTI who have normal renal function and are not obese, traditional doses of 1 g every 12 h are adequate, and trough monitoring is not required (B-II). Thank you, thank you, thank you! Finally, there is some sense in this vancomycin dosing madness. That being said, if you look at Table 3 in the original document at https://cid.oxfordjournals.org/content/early/2011/01/04/cid.ciq146.abstr… ), they do not repeat this. They go back to the “party line” dosing.

65. Trough vancomycin monitoring is recommended for serious infections and patients who are morbidly obese, have renal dysfunction (including those receiving dialysis), or have fluctuating volumes of distribution (A-II). Here is my bottom line about the dosing of vancomycin: If we really need to bump doses this high, I would say it may be time to forget using vancomycin and start using some of the alternative drugs like linezolid (Zyvox, Pfizer), daptomycin (Cubicin, Cubist Pharmaceuticals), ceftaroline (Teflaro, Forest Laboratories) or telavancin (Vibativ, Astellas Pharma). Vancomycin is not some miracle drug we need to keep as a first line therapy and not replace. There are currently six antibiotics FDA approved for cSSTI caused by MRSA. What are we saving them for?

I welcome your comments about these new IDSA MRSA guidelines.

Editor’s note: This blog was originally published at https://www.leinfections.com/category/antibiotics/ and has been adapted with permission from Warren Joseph, DPM, FIDSA, and Data Trace Publishing Company. For more information about the Handbook of Lower Extremity Infections, visit www.leinfections.com/ .