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.