It has been difficult to get any new posts up on the blog lately with an incredibly busy travel/lecture schedule. In the past 2-3 weeks I have been in Toronto for the very successful APMA National, Indianapolis for the Drum Corps International World Championships (not work related for a change!), Las Vegas this past week for 3 well attended lectures and both South Carolina and Georgia Monday and Tuesday of this week. This has not left much time for scanning the recent literature to update the blog.
One question that arises consistently at almost all of these lectures is the role of newer antibiotics in the treatment of osteomyelitis and why none of them are FDA approved. During the course of these talks I invariably ask the audience “name for me an antibiotic FDA approved for osteomyelitis in the past 15 or so years”. This is followed by the usual litany of newer antibiotics being mentioned by audience members. Actually, it is a bit of a trick question. NO antibiotic has received an indication for osteomyelitis in that period of time. Of course, this is not a reflection on the quality or efficacy of the newer drugs, it is just the symptom of the Food and Drug Administration, Center for Drug Evaluation and Research (FDA/CDER) never developing “Guidance for Industry” on how to perform an osteomyelitis trial. What this means is that if Merck, Pfizer, Wyeth, Cubist, whoever, goes to the Agency and tells them they want to receive an indication for osteomyelitis, there are no specific guidelines set by the FDA to tell them what to use for endpoints and how to perform the trial.
Of course, this is an understandable situation given the difficulty this disease presents. Think about this yourself. If you were the FDA, how would YOU want the study to be performed? What are the proper diagnostic criteria? What role, if any, should surgery play? What is the appropriate endpoint? What sort of follow-up should be required to prove the cure or relapse? The potential questions just go on and on.
This is not to say that some companies have not attempted to do a study. A survey of www.clinicaltrials.gov using the search terms “osteomyelitis, diabetic foot infections” yield only two results. Most recently Wyeth attempted to study tigecyline vs. ertapenem +/- vancomycin for diabetic foot infections including osteomyelitis. Clinicaltrials.gov has the study has the study listed as completed but no osteo data has been presented from it to the best of my knowledge. The second study is taking place in France. Removing the search term “diabetic foot infection”, Cubist is currently recruiting patients for a prosthetic joint osteomyelitis study of daptomycin.
So, what is the bottom line? Until the FDA solidifies Guidance on how to do an osteomyelitis trial, especially in the lower extremity, there will be no formal “approvals” for this disease. That does not imply that the drugs released in the past 15 years are any less effective than some of the grandfathered antibiotics with an osteo indication (how many of you realized that cephalexin is “approved” for osteomyelitis?). It just means that the drugs have not been studied to the FDA’s standard and the use is off-label. There are case series in the literature of many of these antibiotics being used successfully for osteo. If the drug hits the bug found in the bone (the single most important determinant of success) then you should feel comfortable using any of these newer antibiotics.