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 “4^th or 5^th 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

After an extended, deliberative writing and review process the brand new Infectious Diseases Society of America clinical practice guidelines on the treatment of MRSA have finally been published (full text at http://cid.oxfordjournals.org/content/early/2011/01/04/cid.ciq146.full.pdf+html).  I really feel that this document is a MUST READ for anyone interested in treating infections of the lower extremity.  For right or wrong clinical practice guidelines are frequently held out to represent the “standard of care” and this document will be no exception.  In fact, these guidelines include an excellent disclaimer frankly stating that adherence to the guidelines is “…voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.”

Overall, this is an excellent piece of work and kudos goes out to lead author Dr. Catherine Liu of UCSF and the committee.  Sitting on an IDSA Guidelines committee, I understand the process.  It could not have been easy to come to consensus particularly in an area of ID that is changing so rapidly and where there is the potential for so much controversy.

Although much of the document pertains to infections other than skin/skin structure and bone/joint I still feel it is important to list those points from the Executive Summary which could have direct impact on a lower extremity infection practice.  With all of the new IDSA Guidelines the required format is “Question, Answer, Evidence Summary”.  I will pick out parts of those that apply to our practice and would ask you please read the entire document for the complete picture.  As you would expect, I will not resist adding my 2 cents! My comments will appear in italics

Question I:  What is the management of skin and soft tissue infections in the era of community-associated MRSA?

1. For a cutaneous abscess I&D is the primary treatment.  For simple abscesses or boils I&D alone is likely to be adequate. I have covered this subject in the past.  The treatment of a CA-MRSA simple (usually defined as <5 cm in diameter) abscess is I&D.  There is essentially no evidence that adjunctive antibiotics are warranted.

2. Antibiotic therapy is recommended for abscesses associated with antibiotic therapy is recommended for abscesses associated with the following conditions: severe or extensive disease (eg, involving multiple sites of infection) or rapid progression in presence of associated cellulitis, signs and symptoms of systemic illness, associated comorbidities or immunosuppression, extremes of age, abscess in an area difficult to drain (eg, face, hand, and genitalia), associated septic phlebitis, and lack of response to incision and drainage alone. This point is valuable in that it actually spells out those conditions where antibiotics should be considered adjunctive to the I&D

3. For outpatients with purulent cellulitis (eg, cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess), empirical therapy for CA-MRSA is recommended pending culture results. Empirical therapy for infection due to beta-hemolytic streptococci is likely to be unnecessary. Five to 10 days of therapy is recommended but should be individualized on the basis of the patient’s clinical response. This is an interesting point in it differentiates “purulent” cellulitis from “nonpurulent” cellulitis (see next point).  Frankly, I am not certain that I have seen that in the past.  Most of what we are seeing in the lower extremity is the purulent variety but, as I write this, I have a patient in the hospital with venous insufficiency and a significant cellulitis of her leg, but with no pus.  Sure enough, cultures of the clear drainage just this morning grew Group B, beta-hemolytic Strep.  (See picture below)

4. For outpatients with nonpurulent cellulitis (eg, cellulitis with no purulent drainage or exudate and no associated abscess), empirical therapy for infection due to b-hemolytic streptococci is recommended. The role of CA-MRSA is unknown. For the patient I just mentioned above, she had been started empirically on vancomycin from the ED, she did not improve to my satisfaction so we added piperacillin/tazobactam and had remarkable improvement within 24 hours. I stopped the vanco. 

5. For empirical coverage of CA-MRSA in outpatients with SSTI, oral antibiotic options include the following: clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), a tetracycline (doxycycline or minocycline), and linezolid. If coverage for both beta-hemolytic streptococci and CA-MRSA is desired, options include the following: clindamycin alone or TMP-SMX or a tetracycline in combination with a beta-lactam (eg, amoxicillin) or linezolid alone. This point really just lists the oral antibiotic choices we knew we had all along.  I would direct you to the documents “evidence summary” to see how little actual data there is backing any of this though.  Furthermore, I am not as enamored with TMP/SMX as the recommendations in these Guidelines and tend to prefer using doxycycline or minocycline.

6. The use of rifampin as a single agent or as adjunctive therapy for the treatment of SSTI is not recommended. I agree and do not use rifampin.  As you will see in the osteomyelitis and prosthetic joint section these guidelines are very “pro” rifampin despite what I feel is a lack of any significant evidence.

7. For hospitalized patients with complicated SSTI (cSSTI; defined as patients with deeper soft-tissue infections, surgical/traumatic wound infection, major abscesses, cellulitis, and infected ulcers and burns), in addition to surgical debridement and broad-spectrum antibiotics, empirical therapy for MRSA should be considered pending culture data. This point it BIG!  They are recommending pretty much ALL patients admitted with cSSTI, which would translate into almost all admitted patients, be started on anti-MRSA therapy.  There is no leeway given for local/regional variations in incidence.  Sure, most of us have been doing this but, frankly, in the past 6 months to a year, most of our admitted patients are NOT growing MRSA at this point.  I have actually started going back to escalation (no MRSA empiric coverage) therapy in some cases. 

Given the importance of this document I would rather break down the discussion into shorter, hopefully more easily digestible portions.  Above I covered the first section on Skin and skin structure infections.  I also want to comment on the bone and joint recommendations which include osteomyelitis, septic arthritis and implant related infections along with my favorite part (see my previous postings on the topic) the recommendations for vancomycin dosing and monitoring.  Stay tuned…

Non-purulent cellulitis casued by Group B beta-hemolytic strep, not MRSA