Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones

Abstract

Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).

Key words::

• Avarofloxacin
• delafloxacin
• EDP-322
• finafloxacin
• oritavancin
• nemonoxacin
• solithromycin
• zabofloxacin

Acknowledgements

F. Van Bambeke is Maître de recherches of the Belgian Fonds de la Recherche Scientifique (FSR-FNRS).

Declaration of interest: F. Van Bambeke has received research grants from The Medicine Company, Cempra Pharmaceuticals, MerLion Pharmaceuticals, and Melinta Therapeutics.

Notice of Correction

Following acceptance of this manuscript and publication online ahead of print on 24 July 2014, FDA approval has been obtained in August 2014 for the use of oritavancin for the treatment of acute bacterial skin and skin structure infections.