As I mentioned in my previous post, this has been a pretty exciting time in the area of lower extremity infectious diseases. Not only do we have 2 new drugs for onychomycosis (to be covered in future posts) but we also have 3 new FDA approved antibiotics for the treatment of, in FDA Speak; “acute bacterial skin and skin structure infections” (aBSSSI). These drugs are tedizolid, dalbavancin and oritavancin. Of these, the one that I am most interested in, at least at this moment, is tedizolid.
Tedizolid phosphate (Sivextro™, Cubist) is an oxazolidinone antibiotic. This is only the second drug in this class to be approved, the first being linezolid back in 2000. As with linezolid, its spectrum of activity is essentially gram positive organisms including MRSA and VRE. The difference between the two drugs is what makes it interesting. Linezolid is dosed 600mg (IV or PO) q12h for 10 days. Tedizolid is dosed 200mg (IV or PO) once daily for only 6 days. By giving the significantly lower dose for a shorter period of time leading to a much lower total drug exposure, some of the more commonly feared adverse events found with linezolid, in particular myelosuppression and possible serotonin syndrome in patients taking SSRIs, look to be significantly lessened, if not totally eliminated. Furthermore, the cost, always an issue when trying to prescribe linezolid, should also be lower.
The two pivotal clinical trials, titled ESTABLISH -1 (oral only) and ESTABLISH-2 (IV with possible switch to oral;
Compared tedizolid 200mg daily for 6 days to linezolid 600mg q12h for 10 days. Both studies found tedizolid to be non-inferior (also FDA speak) to linezolid.
So where does this new drug fit in the treatment of lower extremity infections? Because it was approved under the more recent FDA aBSSSI Guidance as opposed to the previous “complicated skin and skin structure infection” guidance, diabetic foot infections is specifically excluded. This is a flaw in the current aBSSSI guidance document that some of us have been debating with FDA. That does not mean it won’t work in DFI, just that it was not included in the trials. Furthermore, just because there were no DFIs does NOT mean that there weren’t any lower extremity infections. In fact, about 40% of the patients in the trials did, in fact, have infections of the lower extremity including infected ulcers, surgical wounds, abscesses, etc.
Given its narrow spectrum of activity against pathogens we find, shorter duration of therapy and possibly enhanced safety profile, tedizolid seems to fit nicely with current concepts of antimicrobial stewardship. This is one new antibiotic that I feel may have an excellent niche in the treatment of LEIs.