HIV and ID Observations

WPA Recreation Project, 1939

While last week the world was sunning on the beach, hiking in the woods, eating ice cream, and performing careful tick-checks, the hard workers at the Food and Drug Administration hunkered down in Silver Spring, Maryland to get three anti-infectives approved — eravacycline, doravirine, and doravirine/TDF/3TC.

Maybe they saw the weather reports — hot and humid, this is the D.C. area! — and figured they might as well stay inside. Take advantage of the climate control and finish off these applications!

Let’s consider the antibiotic approval first.

As the name suggests, eravacycline is a tetracycline derivative, but with a much broader antibacterial spectrum. This includes many highly resistant gram negatives (including some carbapenem-resistant organisms and acinetobacter), MRSA, VRE, and anaerobes. Pseudomonas aeruginosa is an important exception to its broad coverage.

The drug’s approval was based primarily on clinical trials demonstrating non-inferiority to ertapenem in intra-abdominal infections, and a second study versus meropenem with similar results — hence this is the indication in the label. Treatment for complicated UTIs vs levofloxacin didn’t go well, so the drug is not recommended for UTIs. Because eravacycline is hepatically metabolized, there’s no need for dose-adjustment in renal failure.

As with tigecycline (to which one inevitably draws parallels), gastrointestinal side effects predominate, though appear to be less common — good news, since nausea is far and away the most common dose-limiting side effect for tigecycline. Infusion site reactions are more common than with the carbapenems.

Encouragingly, the company plans to price the new drug at the lower end for a recently approved antimicrobial, bucking a common trend for new drugs.

So we have this new antibiotic — how will it be used?

To echo a common refrain of most recently approved agents, eravacycline will not immediately be a first-line option for its approved indication, intra-abdominal infections.

However, if we get a bit creative, one could envision an important role for eravacycline in certain patient scenarios — with the caveat that some are admittedly speculative and definitely off-label.

Roughly in order of plausibility (most to least), here are several potential treatment settings for eravacycline:

• If tolerability is confirmed in clinical practice to be better than tigecycline, in place of that often troublesome drug.
• In a patient with intra-abdominal infection, documented allergy to beta lactams, and known to harbor fluoroquinolone-resistant organisms.
• For someone at very high C. diff risk — especially if eravacycline proves to be as low risk as other tetracycline-class drugs.
• In therapy of ceftriaxone-resistant gonorrhea — this will need a clinical trial, of course, to establish efficacy and dose.
• For treatment of non-tuberculous mycobacteria, in particular M. abscessus — but first it would be optimal to see in vitro activity, and preferably approval of the oral formulation (regardless of what it’s approved for).

As for the brand name, Xerava — is it just me, or is this a trap for a drug name mix-up?

I’m thinking, of course, of a very widely used oral anticoagulant!