In this entry I will continue to explore some of the new antibiotics that have been recently approved for use in acute bacterial skin and skin structure infections (ABSSSI). I will discuss these two together since they are quite similar in a number of important ways and share many of the same properties.
Both dalbavancin (Dalvance™ – Actavis) and oritavancin (Orbactive™ – The Medicines Company) are classified as “semisynthetic lipoglycopeptide” antibiotics. Both are effective against resistant gram positive organisms including MRSA. They have both been around for quite awhile having been studied and then turned down for approval by the FDA back around 2007-8 citing lack of sufficient data. Both were then dropped by their original companies and eventually picked up by others who finished the study process to get them FDA approved. They also both share similar pharmacokinetics with very long half lives allowing weekly dosing. Dalbavancin is dosed 1 gram IV on day 1 followed by 500mg on day 8, while Oritavancin is given in a single 1200mg IV dose.
In the Phase III clinical trials for dalbavancin, entitled the “Discover 1 & Discover 2 “ trials (http://www.nejm.org/doi/full/10.1056/NEJMoa1310480 ), dalbavancin given in the 2 dose regimen was found to be noninferior to IV vancomycin followed by po linezolid (clinical success 90.6% for Dalbavancin vs. 93.8% for the comparator) with adverse events being less frequent in the dalbavancin group.
Similarly, in the two Phase III trials of oritavancin (http://www.nejm.org/doi/full/10.1056/NEJMoa1310422) the single dose regimen was compared to twice daily IV vancomycin for 7 to 10 days. The primary end point (reduction in lesion size by 20% at 48-72 hours – the current FDA standard and probable topic for a future post) was met in 82.3% for oritavancin vs. 78.9% of the time. Although adverse event rates were similar, nausea was found more commonly in the oritavancin group.
So, where do these drugs fit in terms of our clinical usage in the management of lower extremity infections? As you can imagine, I have my opinions…but you will have to wait for my next post!
