Telavancin (Vibativ – Theravance/Astellas) is a novel lipoglycopeptide, related to vancomycin, that has been recently approved by the FDA for the treatment of complicated skin and skin structure infections (cSSSI) caused by MRSA. Telavancin now joins the ranks of vancomycin, linezolid, daptomycin and tigecycline as being the only 5 antibiotics with this approval. An excellent review of this drug was published by Saravolatz, Stein and Johnson in the December 15, 2009 issue of Clinical Infectious Diseases. Here is a link to the Abstract: http://www.journals.uchicago.edu/doi/abs/10.1086/648438 . I highly recommend anyone interested in this drug to search out this complete article and familiarize yourself with it.
Without going into too much detail (which may infringe on copyright?), I would like to point out a few important take home messages that I got out of this paper and from my review of other literature on the subject. First some of the positives:
1. The usual dose is 10mg/kg q24h. Thus, we have the ease of a once daily dosing
2. The drug is consistently bactericidal against most S. aureus. Various reviews have shown that this probably has little impact in the treatment of cSSSI and may be more important in blood stream infections for which this drug is not approved.
3. It is effective against MSSA, MRSA, VISA and hVISA. It is also effective against daptomycin and linezolid resistant strains. It does not have activity against the most common strains of VRE.
4. Unlike vancomycin, there is no call to monitor serum trough levels
5. In two pivotal cSSSI clinical trials it was found to be “non inferior” (FDA speak) to vancomycin. 63% of the S. aureus strains were MRSA making it the largest number of MRSA patients in a cSSSI study to date.
Now some downsides:
1. It is primarily excreted through the kidneys so significant dosage modification must be made in cases of renal insufficiency. The recommendations are the full 10 mg/kg q24h if the creatinine clearance is >50 mL/min, 7.5 mg/kg if 30-50 and 10 mg/kg q48h if the clearance is <30.
2. Chronic, infected diabetic foot ulcerations were specifically excluded from the two pivotal trials! I don’t see this drug receiving the coveted “…including diabetic foot infections” approval anytime soon.
3. Although the overall safety looked comparable to vancomycin there were higher rates of some significant adverse events including altered taste, nausea and vomiting along with an increase in renal events. On the other hand, vancomycin had higher rates of infusion reactions
4. The drug has received a black box warning for fetal risk.
So what is the bottom line? I agree with the authors of this review that we need new novel antibiotics to combat MRSA especially given all of the increasing reports of vancomycin MIC creep and treatment failures. Many of the drugs that looked promising earlier in their development have either been slowed considerably (ceftobiprole) or stopped totally (oritavancin, iclaprim) so the once fertile pipeline is looking a bit thin. Telavancin gives us one more drug to add to that relatively short list of alternatives to vanco especially with organisms that have developed resistance (although extremely rare) to those other antibiotics. At this early point in its history, I am somewhat concerned about its lack of diabetic foot infection data and its increase in adverse events compared to vanco. The black box may also impact some potential patients. Given that we have other vanco alternatives with years of clinical experience, including diabetic foot data, and well known safety profiles I may feel more comfortable seeing more clinical data and published AE experiences before jumping in with both feet.