I have blogged a number of times about the questions surrounding some of the unknown, unproven issues surrounding the treatment of osteomyelitis including duration of antibiotic therapy and the “need” for surgical debridement. It continues to amaze me how it does not matter where, or to whom I lecture, if I ask the question “How long do you need to treat osteomyelitis and via what route?” the answer is always the same “4-6 WEEKS OF IV THERAPY” despite a total lack of human evidence to support that position. I recently came across an interesting paper that add to the ever increasing body of scientific literature that shows this old axiom is just not justified.   

In the February 2011 issue of International Orthotpedics T. Rod-Fleury and colleagues looked at duration of post surgical antibiotic therapy in adult chronic osteomyelitis.  (http://www.ncbi.nlm.nih.gov/pubmed?term=Rod-Fleury%20T) This is from the same group at Geneva University Hospital that published on the utility of sinus tract cultures on which I commented back in November of this past year.  They retrospectively examined 49 episodes of chronic osteo with a minimum of 2 years follow-up.  I should point out that they specifically excluded diabetic foot osteo.   The patients underwent a median number of 2 surgical debridements.  These were bad cases with almost all being considered Cierny-Mader IV category disease with the patients having a minimum duration of symptoms of 3 months. They found that 80% were in remission at the two year point.  What I feel is important to stress is their conclusion right from the Abstract that, after multivariate logistic regression analysis “one week of intravenous therapy had the same remission as two to three weeks or ≥ 3 weeks.  More than six weeks of total antibiotic treatment equaled ≤ six weeks.”  To quote the conclusion of the paper “If our retrospective results are confirmed, a shorter or oral antibiotic treatment post-debridement could further decrease antibiotic consumption, as well as the related costs, adverse effects and selective pressure for resistant bacterial pathogens.”  Now, this is far from a perfect study and the authors do a commendable job citing the limitations of the study.  Also, they take the almost chauvinistic surgical attitude right in the beginning of the Introduction that “Chronic bacterial osteomyelitis is a surgical disease” (still not totally proven in my mind), but it does again bolster the argument that we need to re-examine this entire 4-6 week IV dogma.

I just returned from the DFCON meeting in Los Angeles, always my favorite scientific conferences of the year (I have blogged about it previously http://www.leinfections.com/diabetic-foot/the-olmos-award-and-dfcon-2010/).  My topic this year was “Drugs and Bugs 2011”.  Since I gave a similar talk last year I had to try to find a few “hot” topics to update the talk.  Without a doubt, the most important development in Infectious Diseases over the past year has been the increasing prevalence of multi-drug resistant organisms (MDRO), in particular the gram negative rods harboring extended spectrum beta-lacatamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC) and the New Delhi metallo-beta-lactamases (NDM-1, NDM-2).  In fact, as I was in my hotel in L.A. polishing up my lecture for later that afternoon of Friday 3/25, I had Good Morning America (GMA) on the TV in the background.  A story was announced on the latest “Superbug”.  These fear-mongering sorts of titles always get my attention so I stopped work on the lecture and listened.  Sure enough, they were reporting on an outbreak of Carbapenem resistant Kleb pneumo (CRKP) in 350 patients right there in Southern California.  Needless to say, it was immediately added to my lecture, although I doubt that Good Morning America would be considered an appropriate peer reviewed, primary reference for a scientific publication! When I arrived home the next day, there was an email from a friend/colleague asking about CRKP since the news headline also hit our local all-news radio station.  I realized that, although I speak about them frequently at lectures, I have never written about them here.  It is past due.

Although I may give a more complete scientific explanation in a future post, I just wanted to pique your interest so that you can do some reading and exploration on your own about this major threat.  In the most basic terms, ESBLs are enzymes that inactivate most current beta-lactam antibiotics including cephalosporins and penicillins.  The most common organism in which the ESBLs are found seem to be E. coli and Proteus mirabilis.  Many of us of a certain generation remember a time when these organisms were so susceptible to antibiotics that you could pretty much choose any drug with basic gram negative activity and it would be effective.  Now, there are isolates of these organism resistant to most commonly used antibiotics and only susceptible to traditionally thought of “big guns” such as carbapenems, and tigecylcine.  And, don’t think these are only found in urinary tract infections, bacteremia, pneumonia or other severe hospital based infections, I have seen them in diabetic foot infections on a number of occasions.

As the name implies, KPCs are enzymes that not only inhibit the previously mentioned antibiotics but also one of the remaining choices effective for ESBLs…carbapenems.  Needless to say, this makes these organisms extremely difficult to treat.  Tigecycline resistance has been reported.  In severe, life threatening infections caused by KPC containing organism the “last ditch” treatment has become either polymyxin-B or colistin.  These are nasty drugs with rather significant adverse event profiles, mostly renal toxicity.  The problem is that, as recently as the past month or two there have been reports of both polymyxin and colistin resistant strains reported in the literature leaving, essentially, no good treatment.  This is why the physician interviewed for the GMA story reported 40%+ mortality related to this organism.  To date the vast majority of these cases are occurring in debilitated hospitalized patients but, the very first KPC in our hospital occurred in a patient I was seeing with a diabetic foot infection. 

 The “MDRO of MDROs” has to be those containing the NDM-1 gene.  This gene was first reported in 2008 in Sweden in a patient hospitalized in India and has a greater ability to rapidly spread to other bacteria than does KPC.  This has become a huge issue in Asia and Europe but has now also spread to the US with, at last count, I believe 4 reported cases.  All patients had some relationship to the Indian subcontinent either having come from there or visited as a tourist.  These bacteria have a similar antimicrobial susceptibility pattern as the KPCs but tend to develop resistance more rapidly.  In the February 2011 issue of Clinical Infectious Diseases an Editorial Commentary says it all just by its’ title “New Delhi Metallo-β-lactamase and Multidrug Resistance: A Global SOS?  http://cid.oxfordjournals.org/content/52/4/485.extract.  To only make matters worse, as recently as last week I saw the first report of an Acinetobacter with a brand new variant, the NDM-2 gene http://jac.oxfordjournals.org/cgi/content/abstract/dkr135v1.   

Unfortunately, there is not a lot of promise for new antibiotic development to fight these MDROs.  The Pharma industry does not make its money on new antibiotic development as most of these drugs are only given for a short period of time in contrast to therapies for hypertension, GERD and cholesterol. To this end the Infectious Diseases Society of America has developed the “Bad Bugs Need Drugs, 10 by 20” campaign  (http://idsociety.org/10×20.htm) a collaboration between the IDSA, Industry and the Government to developed 10 new antibiotics by 2020. I urge all of the readership to check out this website and others to educate yourselves on the risks and dangers these new organisms cause.

I know that sometimes my posts can be a bit esoteric discussing the minutia of antibiotic dosing, findings in the literature, etc.  So, to change gears a bit, I would like to make this a rather basic clinical discussion.  I know that some of you may find this too simplistic but given the number of residents and students who read this blog I feel it is an important topic.

Since the very first edition of my Handbook of Lower Extremity Infections I have made sure that somewhere within the first page or two of text is a statement along that lines that “Infection is a CLINICAL condition and its diagnosis is made on CLINICAL grounds” (pg 4 of the 3^rd edition). You diagnose infection by looking for the classic signs of infection including; erythema, edema, warmth, tenderness, loss of function and purulent drainage.  You then take a culture, not to diagnose the infection, but rather to tell you what organism is causing the infection and what antibiotic you need to treat it.

Of course, this definition is all well and good but there are conditions that mimic these signs and symptoms of infection and are frequently misdiagnosed as such when the patient is admitted to the hospital or seen by their physician. The classic one is an acute gout attack.  In that situation you have essentially all of the requisite clinical findings including drainage but no infection.  I recently was consulted on a patient (unfortunately, I can not find the pictures) who presented with a hot, red swollen first MTP joint admitted with the diagnosis of “cellulitis and osteomyelitis”.  All of the clinical findings were there, but what made me suspicious that his foot was not infected, was the drainage.  Instead of being your typical creamy, runny or smelly pus you see from foot infections the drainage was pure white and chalky.  Furthermore, the x-ray findings looked like the classic Martel’s Sign you see in gouty arthritis with a “rat-bite” appearance. Along with sending off a culture, which came back as no growth, we also sent the drainage to pathology for microscopy.  As expected, crystals were found. I was able to discontinue the IV antibiotics.

Another favorite of mine is the patient admitted for “cellulitis” of the foot when, in fact, it is severe dependency rubor from peripheral arterial disease.  I saw a patient about 3 weeks ago admitted for gangrene of the 4^th toe and cellulitis.  Certainly, the toe was gangrenous and there was quite an odor coming from the foot since the patient had not bathed or changed clothes in quite awhile.  There was also some slight drainage coming from between the toes but this was not causing the significant erythema the patient exhibited.  This patient had the most marked “rubor on dependency, pallor on elevation” (Samuel’s Test) I had ever seen. Usually the color change may take a few minutes but in this patient it was almost immediate.  His foot blanched totally.  A true infectious cellulitis will not behave this way and residual erythema will still be seen.  Cultures only grew diptheroids (which CAN be pathogenic and a topic for a different post).  Unfortunately, the patient refused all vascular testing and was discharged back to his bording home.

The third example I want to use is the patient admitted with “cellulitis of bilateral legs”.  The most recent patient I saw with this diagnosis was about 250 lbs and sat in a chair almost all day with her legs in a dependent position.  She presented with massive edema of both legs, marked erythema bilaterally and multiple serous filled vesicles around the circumference of the her legs. She had been admitted on IV antibiotics.  When I saw the patient on consultation it was my opinion that the patient and venous insufficiency and not an infection.  True infectious cellulitis does not usually occur as a bilateral and symmetrical condition.   When I spoke to the attending I got push-back on that diagnosis since, afterall, the patient “was doing well on IV antibiotics” with reduction in both the erythema and edema.  Of course, IMHO the patient was doing well, not because of the IV antibiotics but because she was IN BED with her LEGS ELEVATED!

A key buzzphrase in the infectious diseases community nowadays is “Antibiotic Stewardship”.  Although much has been written about it and, at least in California it is now mandated that hospitals develop stewardship programs, the concept is fairly straightforward.  Basically, it means that antibiotics should only be used when appropriate and then the right drug should be employed for the diagnosis. The most fundamental idea I would put forward is that sometimes “infections” are not infections and antibiotics are not necessary.

I am sure that all of you reading this can think of other similar situations.  PLEASE SHARE your thoughts!

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

One of this blog’s readers, Dr. McLeod, asked the following:

My question is: Does one need to prescribe antibiotics after I+Ding an abscess? I use to work at a county hospital in Oakland, California  where there was a high MRSA rate. At that time (2005), we were being taught not it is unneccessary to prescribe antibiotics after I+Ding an abscess, other than to practice defensive medicine. But, is it necessary to prescribe antibiotic in your opinion after an abscess I+D? I am talking about a classic abscess, not a cellulitis of any form.

This is an excellent question that allows me to go off in two directions.  First, to directly answer Dr. McLeod’s question, NO, the evidence is fairly strong that I&D of an abscess of <5cm in diameter without concomitant antibiotic therapy is considered adequate and appropriate therapy for an MRSA abscess.  For one of the first studies that really showed this, and the one that was probably quoted by the folks with whom you worked in 2005, I direct you to the 2004 paper by Lee et.al in the Pediatric Infectious Disease Journal (PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14872177)

The 2^nd direction or “tangent” I want to explore with this entry has more to do with the follow up of this type of patient, or for that matter any infection patient.  The question is “How long do you need to continue antibiotic therapy?”

A few years ago I was sitting in on a lecture at the annual meeting of the Infectious Diseases Society of America.  Unfortunately, I can’t remember the speaker in order to give appropriate credit but what has stuck with me ever since is the concept he proposed: Why do we continue to routinely give 10-14 day prescriptions of antibiotics when the infection may be clinically cured in 2-3 days? Rather we should consider the concept of giving the patient antibiotics until clinically better and then for only another 2-3 days an idea that can be called “Better Plus 2”. 

Think about this…you automatically give someone a 7, 10, 14 day Rx for an antibiotic.  What do you tell them as you hand them the script?  “Make sure you take it until it is all finished”.  Heck, it even says it right on the bottle the patient receives from the pharmacy!  WHY?  Because we have been taught that is the way to prevent resistance development. Now, let’s look at the patient proposed by Dr. McLeod above.  You I&D that abscess AND give antibiotics for 10 days solely because this is what you have been taught or you want to practice defensive medicine, or whatever reason.  You see the patient back on Day 3 and the wound looks great.  The abscess and any surrounding cellulitis are gone BUT the patient still has 7 days of antibiotic to go; an antibiotic that is not medically necessary because the patient is clinically cured.  Think about it; how do we develop antibiotic resistance?  By giving an antibiotic when it isn’t necessary!  Is this a greater risk than stopping the antibiotic too early, I would venture an opinion that, yes, it is.

As you know from reading my posts, I am a believer in backing up what I write about with literature/science. Before writing this entry I tried to find some substantiation for this concept in the literature.  On my cursory PubMed search nothing came up. It may or may not be out there and I just could not find it.  If anyone is familiar with support for this concept please let me know. It is just one of those ideas that make perfect sense to me.  There is nothing of which I am aware supporting the routine use of 10-14 days of antibiotics, at least in skin and skin structure infections, so why should Better Plus 2 be any less valid or legitimate? I wanted to throw this out for you to ponder the next time you write that rote duration on your antibiotic Rx.

Well, the comments have come in and this is what I received – my comments, if any, are in italics:

- Interesting question as I just received a memo from the dental school at the University asking my preferences regarding antibiotic prophylaxis with implant (hardware) patients and dental surgery. The letter outlined the 2003 decision with the ADA and AAOS as well as followup decisions by both organizations. My take is that one has no choice but to recomend AP due to the medical-legal questions. There is little evidence suggesting it is required but one has to take this time honored procedure into consideration.  This is an interesting point.  Originally, the ADA and AAOS actually came out in a joint statement and concluded that it was NOT routinely needed to prophylax a patient for dental work even if they have a prosthetic joint unless the patient was undergoing a “high risk” dental procedure. As recently as Nov 2009 they changed their position to recommend prophy in these patients prior to any dental procedure!  As you will see below, this is not supported by science. As to the medico-legal issue, there is no question that this does come into play, unfortunately, when making medical decisions.  I think it is time (call be an idealist) we should practice medicine based on science and not fear of repercussions.

- No to both unless prior infection. Actually, this is the “correct” answer based on the paper I will share with you below.

- Related question: 30 yo F w/ Mitral Valve Prolapse. Need ABX prophy for foot or ankle surgery w/ or wo/ implants? Absolutely NONE!  The American Heart Association guidelines for prophylaxis against endocarditis are clear on this point (I think I see another blog post idea).  In 2007 they backed off many recommendations for prophy and now only recommend it when surgically manipulating an actual infection (abscess, cellulitis, etc) in a patient with a “high risk” for infective endocarditis.  These high risks are mostly prosthetic heart valves and other major cardiac conditions and do NOT include MVP. Clean elective surgery through surgically prepared skin has not required prophy since their 1997 Guidelines.

- No to both of these questions. If they had a tooth abscess then I may consider. As far as I know they don’t have people with foot/knee/hip implants take abx everytime they brush their teeth. I Think in the case of bunion surgery on a patient with a known knee prosthesis that preop Ancef is enough. Great point! The issue is the development of bacteremia.  This occurs every time someone brushes their teeth, flosses, eats hard food. You don’t prophy with each of these activities so there is no reason to do it for surgery.  Only when an infection is being manipulated should it be considered.

- In the first scenario, if the patient is immunocompromised in any way, I would advise a cephalosporin. Good suggestion.  Interesting “immunocompromise” of the patient does not seem to come up in any guideline.  I don’t know why.

- In the second scenario, since the joint implant is less than 2 years old, I would recommended prophylactic antibiotics.  Excellent point!  The 2 year rule has been around for a while.  It is presumed that if the implant is in place less than 2 years there is a higher risk of it getting infected.  I am not really certain where that comes from or the validity of it. My only issue would be that if you are not manipulating and infection and are doing your bunion surgery through surgically prepared skin, there should be no bacteremia and no reason to give prophy…just like if it was for endocarditis.

I want to thank those who took the time to respond.  I really enjoyed reading, and thinking about your comments. 

Now here is why I brought it up in the first place:  In the January 1, 2010 issue of Clinical Infectious Diseases there is a study by Berbari et.al. out of the Mayo Clinic entitled “Dental Procedures as Risk Factors for Prosthetic Hip or Knee Infection: A Hospital-Based Prospective Case-Control Study.  (PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19951109 ) .  This elegantly done study looked at 339 patients admitted with prosthetic joint infections (PJI) vs. 339 admissions of patients with non infected prosthetic joints.  They examined dozens of parameters including; the type of dental procedure, time from implant to the dental procedure, time from dental procedure to current admission, operative factors, diabetes, immunocompromise, organisms recovered and many others.  I think it is important for you to read verbatim what they stated in the Results and Conclusion parts of their Abstract:

RESULTS: A total of 339 case patients and 339 control subjects were enrolled in the study. There was no increased risk of prosthetic hip or knee infection for patients undergoing a high-risk or low-risk dental procedure who were not administered antibiotic prophylaxis (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (adjusted OR, 0.6; 95% CI, 0.4-1.1) respectively. Antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee infection (adjusted OR, 0.9 [95% CI, 0.5-1.6] and 1.2 [95% CI, 0.7-2.2], respectively).

CONCLUSIONS: Dental procedures were not risk factors for subsequent total hip or knee infection. The use of antibiotic prophylaxis prior to dental procedures did not decrease the risk of subsequent total hip or knee infection.

They go on to question the recent AAOS recommendations since they were seemingly not based on any science.  They recognize in the manuscript: “Although the adverse risk of antibiotic prophylaxis in the individual patient may seem remote and unlikely, the risk to the overall population with a joint arthroplasty and to society at large seems prohibitive”.  I believe that this is something we forget when making decisions on our individual patients.  We do thing, like give possibly unnecessary antibiotics to “cover ourselves” from medico-legal concerns and because, frankly, it probably will not hurt that one patient.  But when you multiply your actions times thousands of practitioners thinking the same thing, times the 10s of thousands of patients being treated we start to have an impact on the global microbiota. 

I urge my readers to seek out this article since there are lots of other interesting points that are made and I don’t have the space to go into with this post.

With this blog entry I am going to try something a bit different.  I know that there is a good readership of my posts but, to date, I have been somewhat disappointed in the number of comments and interactions I have received from you, the readers.  I stated in my very first post:

The whole idea of this blog is to be interactive.  I want to hear others’ thoughts and ideas!  This is what will make it intellectually stimulating and fun for me and, hopefully, valuable to those monitoring the site

To this end I would like to start a “What Would You Do?” entry.  I will ask a clinical question or two, maybe present a case, and ask you for feedback on what you would do in this situation.  Give me your thought processes that lead you to your position.  Then, in a subsequent post I will review the responses and give you my approach along with any pertinent clinical evidence I have to back it up.

Let’s start with this; a recent very well done study was published on dental procedures and prosthetic joint infections (I will not give you the reference yet. That will hold until the answers come in) that may alter the way we look at antibiotic prohylaxis in these situations.  So, here are the questions/clinical scenarios I have for you:

1.  You placed a prosthetic joint into a patient’s foot.  Or, let’s even expand it out since there aren’t as many joints being placed anymore, you placed some hardware into a patient’s foot while doing surgery on that foot.  Let’s say the surgery was 18 months ago.  The patient calls you because she is going to the dentist for some dental hygiene and to have a crown placed on a tooth.  DO YOU, OR DON’T YOU, RECOMMEND ANTIBIOTIC PROPHYLAXIS FOR THIS PATIENT BEFORE THE DENTAL WORK?

2.  A patient comes to see you for the chief complaint of a bunion.  You discuss surgical correction.  After the patient agrees to have the surgery scheduled she informs you that she had a prosthetic knee implanted 18 months ago.  DO YOU PLACE THE PATIENT ON PROPHYLACTIC ANTIBIOTICS TO PREVENT A PROSTHETIC JOINT INFECTION FOLLOWING YOUR FOOT SURGERY?

OK, have at it.  There are really no right or wrong answers (or, maybe there are…it depends on the answers I get).  Once I receive some input I will give you my thoughts on the subject and give a summary of this recent study to which I referred above.

I received this question from a reader: In suspected osteomyelitis do you stop antibiotics prior to obtaining a bone culture? For how long?

This comment came in under my entry on the VULCAN trial but I actually covered the question in a post almost exactly a year ago.  I am reprinting my response here for more recent readers who may not have reviewed all of the earlier posts I will also summarize my current thinking at the bottom:

The question of whether or not the patient needed to be off of all antibiotic therapy prior to the culture was always less clearly delineated.  It was almost an empirical belief that if a patient was on antibiotics at the time of the culture then the results would be unreliable.  After all, if a culture is reported as showing “no growth” was this because the specimen was poor, the patient never had osteomyelitis in the first place, or the antibiotics had prevented the organism from growing?

A recent study by Louis Bernard and colleagues out of University Hospital of Geneva Switzerland, and published in the September 6, 2009 issue of the International Journal of Infectious Diseases challenges much of what we currently hold as sacrosanct.  In this non-randomized, prospective trial 141 patient with 154 episodes of osteomyelitis each underwent 4 microbiological samplings.  Sample “A” consisted of 2 consecutive sinus tract cultures with bone contact (“A1” & “A2”) after only local cleansing of the sinus tract with 0.9% saline.  Sample “B” consisted of a surgical bone biopsy through the sinus.  Sample “C” was a surgical biopsy obtained through an uninfected sited, referred to as the “gold standard”.  Their results showed that when both sinus tract cultures “A1 & A2” revealed the same organism the concordance between “A” and gold standard “C” was 96%.  They calculated the sensitivity as 91%, specificity as 86% and accuracy as 90%.  On top of that, they found that the result was not affected depending on whether the patient was on antibiotics prior to the cultures or not.

In their Discussion the authors go out of their way to state that “in no way should these consecutive deep sinus tract specimens replace bone culture in situations where a biopsy can be readily obtained because bone culture remains the gold standard for the microbiological diagnosis of osteomyelitis”.  There are sometimes, however, when a surgical culture is just not practical and that patient has already been started on antibiotic therapy, as the authors call it “clinical reality”.

Since this original post, my thought process has not changed much.  I still believe that, if they have not yet been started, it is best to HOLD antibiotics if at all possible, until after the patient is taken to the OR for deep bone (or, for that matter, soft tissue) cultures. The “real world” gets involved, however, when you admit a patient through the Emergency Dept for the stated diagnosis of “infection” and do not plan on taking the pt to the OR until the next day. Unfortunately, in a case like this, you cannot realistically hold antibiotics or the hospital runs the risk of losing the admission.  If the patient is going to the OR later the same day then I believe in holding the drug unless the pt is sick i.e. metabolically unstable, systemically unwell or septic.

What if the patient has already been started on antibiotics?  Conventional wisdom still calls for the pt to be off antibiotics for at least 48 hours.  I don’t believe there is any evidence to support that thinking.  The Bernard study cited above does give us some hope that it doesn’t matter if the patient is still on antibiotics or not but I would still recommend, again if at all possible, taking the patient off the drugs for as long as it is feasible. Heck, I would go for a week if you can.  There is no magic to 48 hours.  The problem is that if the culture is negative, you don’t know whether it is negative because it is not osteo or if it is negative just because of the antibiotics.  Also, the International Working Group on the Diabetic Foot (www.iwgdf.org) has shown in their diabetic foot osteomyelitis guidelines that the only independent factor leading to a positive response to antibiotic therapy for osteo is bone culture directed antibiotic therapy.  We could really use those deep reliable cultures!

Well, as I expected and predicted in my previous post, the FDA did not waste much time approving ceftaroline (trade name – Teflaro) for complicated skin and skin structure infections (cSSSI).  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm231594.htm (thanks to Lee Rogers, DPM for forwarding me this link).  What does this mean for those of us treating lower extremity infections? It is hard to say.  As I discussed in my September 27 post, the clinical trials actually excluded diabetic foot infections (DFI) and decubitus ulcerations but still managed to include lower extremity infections as almost ½ of their cases.  Because of this, I am guessing that Forest, the company marketing the drug, may be reluctant to call on us for fear that by doing so it may be perceived that they are de facto promoting DFI.   I have seen this with other drugs.  When Schering-Plough was selling Avelox (moxifloxacin, now with Merck) although it would be an excellent drug for DFI given the broad spectrum of activity including anaerobes, the company would not market to podiatric medicine for since they only had the cSSSI indication and not the DFI addition.  I do not know any of the folks at Forest and do not know how aggressive they may be in their marketing campaign so this all remains up in the air.  I am hoping that given the number of lower extremity infections that were included in their trial, they see the value in calling on those of us treating these infections.

Ceftaroline now becomes the 6^th antibiotic FDA approved for the treatment of cSSSI caused by MRSA.  It is the first cephalosporin with this indication which is both good and bad.  It is good because it seems to have a typical cephalosporin safety profile, which is to say, very safe with only a few adverse events noted in the trials and nothing untoward was found.  Most clinicians are really comfortable with this class of antibiotic.  It is also broad spectrum including gram negatives but without Pseudomonas.  Most of the other anti-MRSA drugs, with the exception of tigecycline, are pretty limited to gram positive cocci.  The downside is that cephalosporins are not the “golden child” they once were.  I know that my personal use has declined significantly.  The greatest problem is that these drugs can lead to an increasing incidence of some of the new multi drug resistant gram negative rods including E. coli, P. mirablis and Klebsiella that produce “extended spectrum beta-lactamase” (ESBL) or Klebsiella pneumonae carbapenemase (KPC).  Although usually found in sick patients in the ICU, I have started to see these cropping up in lower extremity infections.  Heck, even Katie Couric did a piece on these new “Superbugs” on her evening news show.

The bottom line is that ceftaroline (Teflaro) should be a welcome new addition to treat mixed infections including those containing MRSA.  Where it will pan out to treat lower extremity infections, and in particular DFI, and the attention Forest pays to those of us treating these infections, remains up in the air.