For part 2 of this posting on the new Infectious Diseases Society of America (IDSA) MRSA Guidelines I would like to comment on some of the Executive Summary points made about MRSA bone and joint infections and also vancomycin dosing recommendations. I will use a similar format as before with posting the actual text and then adding my comments in italics. Unlike the previous post I have decided to keep in their evidence grading so you can determine for yourself whether or not you feel the recommendations are of a high enough level of medical evidence. I have also left the numbering intact so that you can compare it to the original document found at: http://cid.oxfordjournals.org/content/early/2011/01/04/cid.ciq146.full.pdf+html
V. What is the management of MRSA bone and joint infections?
36. Surgical debridement and drainage of associated soft tissue abscesses is the mainstay of therapy and should be performed whenever feasible (A-II). A recommendation made with a high level of evidence that supports the common thinking that surgery is important when practical. I added the “when practical” because of the increasingly strong body of evidence that supports “medical” or non surgical therapy of osteo. That being said, those studies have not specifically looked at MRSA. Whether or not surgery is any more important in MRSA osteomyelitis as compared to other organisms has not been established.
37. The optimal route of administration of antibiotic therapy has not been established. Parenteral, oral, or initial parenteral therapy followed by oral therapy may be used depending on individual patient circumstances (A-III). Much like I have lectured and written on in the past, the whole “6 weeks of IV therapy” thing has never been based in any good human evidence. In fact, newer and stronger evidence points to alternative regimens like oral alone or short course parenteral followed by oral as effective. I am pleased to see this recognized in this document.
38. Antibiotics available for parenteral administration include IV vancomycin (B-II) and daptomycin 6 mg/kg/dose IV once daily (B-II). Some antibiotic options with parenteral and oral routes of administration include the following: TMP-SMX 4 mg/kg/dose (TMP component) twice daily in combination with rifampin 600 mg once daily (B-II), linezolid 600 mg twice daily (B-II), and clindamycin 600 mg every 8 h (B-III).
39. Some experts recommend the addition of rifampin 600 mg daily or 300–450 mg PO twice daily to the antibiotic chosen above (B-III). For patients with concurrent bacteremia, rifampin should be added after clearance of bacteremia. This is where I find it gets interesting. Yes, I have known about the concept of adding rifampin to other antibiotics to treat MRSA (NEVER use it single agent. Resistance develops rapidly) but I have never used it nor felt it was all that necessary. I am surprised to see it mentioned numerous times in this document. It is listed not only here but also in the “osteoarticular device” related infection section. Notice the level B-III rating. This means “moderate level of evidence and a recommendation based on expert opinion, clinical experience…” not randomized controlled trials. In fact, if you look at the “evidence summary” section that covers rifampin, I remain not terribly convinced. I will have to see if I start incorporating it into my treatment.
40. The optimal duration of therapy for MRSA osteomyelitis is unknown. A minimum 8-week course is recommended (A-II). Some experts suggest an additional 1–3 months (and possibly longer for chronic infection or if debridement is not performed) of oral rifampin-based combination therapy with
TMP-SMX, doxycycline-minocycline, clindamycin, or a fluoroquinolone, chosen on the basis of susceptibilities (C-III). Again, rifampin is added to oral regimens. This recommendation contains even a lower evidence rating of “C” meaning “poor evidence to support a recommendation”
41. Magnetic resonance imaging (MRI) with gadolinium is the imaging modality of choice, particularly for detection of early osteomyelitis and associated soft-tissue disease (A-II). Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) level may be helpful to guide response to therapy. Nothing particularly remarkable here. I left it in for completeness sake.
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 that this is a valid measure. What concerns me is that many pharmacists and IDs have taken this to heart and are significantly increasing vancomycin doses and maintaining troughs of 15-20 despite little evidence of increased efficacy and, IMHO 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 OK in bacteremia and pneumonia but I am not at all comfortable with these recommendations in our diabetic patients, probably with preexisting renal problems. I will “split the difference”. I AM OK with keeping the trough between 10-15. 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 (eg, those with sepsis, meningitis, pneumonia, or infective endocarditis) with suspected MRSA infection, a loading dose of 25–30 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 “4th or 5th 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 lg/mL are recommended (B-II). I don’t know why “osteomyelitis” is frequently put in the same category as necrotizing fasciitis. There are so many varieties of osteo in so many locations; I can’t just classify it this way. I do not bump my vanco doses/levels for osteo just because it is osteo.
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, some sense in this vanco dosing madness. That being said, if you look at Table 3, 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, daptomycin, ceftaroline or telavancin. Vancomycin is not some miracle drug we need to keep as first line therapy and not replace. There are currently 6 antibiotics FDA approved for cSSTI caused by MRSA. What are we saving them for?
I welcome your comments about these new IDSA MRSA guidelines