The solithromycin journey-It is all in the chemistry.
The macrolide class of antibiotics, including the early generation macrolides erythromycin, clarithromycin and azithromycin, have been used broadly for treatment of respiratory tract infections. An increase of treatment failures of early generation macrolides is due to the upturn in bacterial macrolide resistance to 48% in the US and over 80% in Asian countries and has led to the use of alternate therapies, such as fluoroquinolones. The safety of the fluoroquinolones is now in question and alternate antibiotics for the outpatient treatment of community acquired bacterial pneumonia are needed. Telithromycin, approved in 2003, is no longer used owing to serious adverse events, collectively called the 'Ketek effects'. Telithromycin has a side chain pyridine moiety that blocks nicotinic acetylcholine receptors. Blockade of these receptors is known experimentally to cause the side effects seen with telithromycin in patients use. Solithromycin is a new macrolide, the first fluoroketolide, which has been tested successfully in two Phase 3 trials and is undergoing regulatory review at the FDA. Solithromycin is differentiated from telithromycin chemically and biologically in that its side chain is chemically different and does not significantly block nicotinic acetylcholine receptors. Solithromycin was well tolerated and effective in clinical trials.
Cempra Inc., Chapel Hill, NC 27517, USA. Electronic address: pfernandes@cempra.com.
Prabhavathi
P
Fernandes
Cempra Inc., Chapel Hill, NC 27517, USA.
Evan
E
Martens
HiQScreen Sàrl, 1222 Vésenaz, Geneva, Switzerland.
Daniel
D
Bertrand
Cempra Inc., Chapel Hill, NC 27517, USA.
David
D
Pereira
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018942:Macrolides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D014230:Triazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D018942:Macrolides; D014230:Triazoles; C547755:solithromycin
Antibiotic-resistance; Fluroketolide; Macrolide; Pneumonia; Solithromycin