Omadacycline for Acute Bacterial Skin and Skin-Structure Infections

RCT (n=316) found that omadacycline, an aminomethylcycline antibiotic, was noninferior to linezolid (IV with transition to oral after 3 days each arm for total of 7-14 days) with respect to early clinical response (84.8% vs. 85.5%, respectively), with a similar safety profile.

This is one of two phase 3, double-blind, randomised clinical trials of omadacycline in the New England Journal of Medicine. The other one involved patients with community-acquired bacterial pneumonia, which reported non-inferority to moxifloxacin for early clinical response (81.1 and 82.7%, respectively).

 

According to an editorial, omadacycline has few advantages over the numerous agents already available for the treatment of acute bacterial skin and skin-structure infections. It notes the benefit, if any, of its activity against susceptible gram-negative organisms was untested because patients with a sole gram-negative pathogen at baseline were excluded from analysis. In addition, linezolid, the comparator, which lacks such activity, performed as well overall, and there were too few patients with mixed infection for a meaningful analysis. It suggests the oral formulation of omadacycline may offer an advantage in certain circumstances — for example, it could be given instead of linezolid as treatment for the occasional patient receiving monoamine oxidase inhibitor or antiserotonergic antidepressant therapy.

 

The editorial also discusses the role of omadacycline for treatment of infections caused by multiple-drug–resistant pathogens. It notes that it does not have cross-resistance with beta-lactam antibiotics, aminoglycosides, polymyxins, and fluoroquinolones and is active against organisms expressing tetracycline efflux and ribosomal protection genes. Also it is many times more active than doxycycline and minocycline against Enterobacteriaceae and Acinetobacter baumannii. It calls for well-designed clinical trials of omadacycline for the treatment of infections caused by multiple-drug–resistant gram-negative pathogens to determine its real value as an antibacterial agent.

 

Omadacycline was approved in the US for the treatment of adults with acute skin and skin structure infections or community-acquired bacterial pneumonia in 2018. A licensing application was been submitted to the European Medicines Agency in October 2018.