It has been about 2 weeks since my first post about ICAAC which has given me some time to ruminate a bit over the happenings there. I have always enjoyed this meeting because its emphasis on new antibiotic development, an area of great interest to me. It is sometimes a bit short on clinical information relevant to lower extremity infections and this year was no different. In fact, other than my poster on the use of daptomycin in diabetic foot infections there were only two other posters, out of thousands, in which the term “diabetic foot infection” even appeared. Both of those studies supported the efficacy of linezolid in the treatment of DFI caused by MRSA. To review some other information I found interesting:
1. During a major symposium on the treatment of gram positive infections, Robert Moellering, MD, one of the gram positive deities in the ID world from Harvard, discussed vancomycin dosing with a lecture entitled “New Approaches to Vancomycin Dosing: Does a higher trough help”. He discussed the new guidelines suggesting troughs between 15-20, a topic I have addressed in this blog. Once again, at least to me, it became clear that the data to support this is very limited, is based on a pharmacokinetic theory, and mostly deals with pneumonia. Dr. Moellering suggested using the vancomycin MIC as a surrogate marker for the appropriate trough for which to aim. The most surprising statement he made was that for an MRSA with a vanco MIC of >1 there is no way to achieve a high enough trough that would still be safe and alternative treatments should be considered (my emphasis). Considering many of us don’t remember the last time we saw an MIC of <1, maybe it is time to finally put vanco to bed??
2. During that same symposium another speaker, David Snydman, MD out of Tufts, discussed linezolid and daptomycin resistance reports. What I found most interesting out of this lecture is that, even after 9+ years of clinical use, the current resistance rates of MRSA for linezolid are sitting at 0.03%. This is a pretty amazingly low number that belays the conventional wisdom, stated throughout the Handbook, that the bugs are always going to be smarter than us. In fairness, resistance rates of coagulase negative staphylococci to linezolid are higher, in some series approaching 5%.
3. I don’t know if the timing of the announcement coinciding with ICAAC was planned or not, but it was announced that another antibiotic, Telavancin, has been approved by the FDA for the treatment of complicated skin and skin structure infections caused by MRSA. This makes the 5th drug for this indication behind vancomycin, linezolid, daptomycin and tigecylcine. Telavancin (Vibativ), developed by Theravance and Astellas, is an IV only lipoglycopeptide. I saw some of their early data a few years ago but am not up on the latest so I really don’t know how to place this drug yet. I am also concerned about some adverse event rates and black box warnings. More to come in the future on this one.
4. An upstart out of the UK, NovaBiotics, presented 2 posters on a “novel fungicidal peptide” for the treatment of onychomycosis. This was really preliminary, mostly in vitro stuff but I do think that the entire peptide class of antibiotics show promise for lots of different applications (can anyone remember Pexiganin?).
5. David Nicolau, PharmD out of Hartford, has done some great work in skin and skin structure infections. Amongst the many posters he presented was one that looked at the development of carbapenem resistance to Pseudomonas aeruginosa when 25 hospitals started using ertapenem. His results echo that of previous authors who have shown time and time again that Pseudomonal cross resistance to other carbapenems does not occur just because a hospital uses ertapenem. This has been a concern voiced by many ID specialists and pharmacists effectively blocking the use of this once daily drug in many hospitals specifically in diabetic foot infections. It is one of only three drugs (along with linezolid and piperacillin/tazobactam) currently approved for this indication.
Well, that is it for my review of ICAAC. Sorry for the long post but I wanted to get as much information as I could out to you in a timely manner.