Solithromycin is a next-generation oral and intravenous fluoroketolide in development for the treatment of moderate to moderately-severe community acquired bacterial pneumonia ( CABP ) and urethritis.
A phase 3 clinical trial of Solithromycin oral capsules met its primary and secondary objectives in the treatment of CABP.

Macrolides are antimicrobial drugs that are active against aerobic and anaerobic Gram-positive cocci and are prescribed for the treatment of respiratory tract and soft tissue infections.

Macrolides belong to the polyketide class of natural products. The macrolide ring, a large lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, are attached, is responsible for the antimicrobial properties of this class.
By reversibly binding to the 50S subunit of the bacterial ribosome, these drugs block protein synthesis, preventing bacterial growth and reproduction. This action is primarily bacteriostatic, however at higher concentrations, macrolides can be bactericidal.
Some of the most commonly prescribed macrolides include Erythromycin, Azithromycin ( Zithromax ) and Clarithromycin ( Biaxin ).

Ketolides belong to the macrolide class that is used to treat respiratory tract infections. These drugs are effective against macrolide-resistant bacteria because of their ability to bind to two sites on the bacterial ribosome. Examples include Telithromycin ( Ketek ) and Cethromycin.

The spectrum of activity of macrolides includes streptococci as well as atypical bacteria such as Mycoplasma and Legionella and intracellular bacteria such as Chlamydia.

Acquired bacterial resistance to macrolides occurs primarily through post-transcriptional methylation of the 23S bacterial ribosomal RNA. This results in cross-resistance to macrolides, lincosamides and streptogramins.
Although rare, acquired resistance can also result from the production of drug-inactivating enzymes such as esterases or kinases, as well as the production of active ATP-dependent efflux proteins that transport macrolides out of the cell.
As more than 45% of pneumococci are resistant to currently available antibiotics, a new macrolide is greatly needed.

Solithromycin is a highly potent next-generation macrolide, the first fluoroketolide, which has potent activity against most macrolide-resistant strains.
In vitro and in vivo studies have shown potent activity against Streptococcus pneumoniae as well as an extended spectrum of activity against CA-MRSA, enterococci, Mycobacterium avium and in animal models of malaria. It is also active against atypical bacteria, such as Legionella, Chlamydophila, Chlamydia, Mycoplasma and Ureaplasma and against gonococci and other organisms that cause genitourinary tract infections.
It is 8-16 times more potent than Azithromycin and is active against Azithromycin-resistant strains. Its activity against resistant strains is driven by its ability to bind to three sites on the bacterial ribosome, compared to one or two for current macrolides.
The binding to three ribosomal sites is expected to limit resistance development.

Solithromycin does not contain a pyridine in the side chain of the molecule ( as does Telithromycin ) that appears to interact with nicotinic acetylcholine receptors and could be associated with serious adverse events such as visual disturbances and exacerbations of myasthenia gravis that have been observed with Telithromycin. ( Xagena )

Source: Cempra, 2015

XagenaMedicine2015