The rise in resistant bacterial strains has highlighted an ongoing need for new antibiotics. A new macrolide antibiotic, solithromycin, is being developed by US biotech company Cempra Pharmaceuticals.1 The fluoroketolide is being developed to treat both community-acquired bacterial pneumonia and gonorrhoea, and unlike the prototype ketolide, telithromycin, it does not appear to cause liver injury or visual disturbances. It is active against some of the most challenging resistant bacteria, such as MRSA and vancomycin-resistant enterococci.
A pooling of Phase I and II data indicated its safety. Subjects from a Phase I trial in 171 healthy subjects and 64 patients with pneumonia were given the drug in oral doses, with exposure up to 4200mg over seven days.2 Across all the studies, the most common adverse events were diarrhoea (13%), headache (13%) and nausea (10%), most of which were mild. Similarly, 91 healthy subjects received intravenous doses of the drug in a Phase I trial, with up to a single 1000mg dose, with lower levels of diarrhoea and nausea, and a slightly higher level of headache. No significant safety concerns emerged across these trials.
In a Phase II, double blind, randomised, efficacy and safety study, 132 patients with community-acquired bacterial pneumonia were given 800mg oral doses of solithromycin on day one followed by 400mg for the next four days, or 750mg oral levofloxacin for five days.3 Comparable activity was seen between the two antibiotics – an early clinical response was achieved in 47 of 65 patients given solithromycin, and 48 out of 67 in the levofloxacin group. More of the subjects given levofloxacin experienced at least one treatment-related adverse event – 46% compared with 30% for solithromycin.
It is also being investigated in uncomplicated urogenital gonococcal infections. Phase II trials are under way, with the drug having shown in vitro activity against antibiotic resistant Neisseria gonorrhoeae isolates.
References
1. C. Hwang et al. Antimicrob. Ag. Chemother. 2008, Abst. F1-3973
2. D. Oldach et al. Intersci. Conf. Antimicrob. Ag. Chemother. 2012 (San Francisco, Sep 9-12), Abst. A-1286
3. D. Oldach et al. Intersci. Conf. Antimicrob. Ag. Chemother. 2012 (San Francisco, Sep 9-12), Abst. P-719
