New quinolones in development

Abstract

Fluoroquinolones, such as ciprofloxacin and ofloxacin have recently gained wide acceptance for use in the treatment of respiratory tract, skin/soft tissue, sexually transmitted diseases and urinary tract infections. The broad spectrum activity and good oral absorption characteristics of these antimicrobials promotes their use in both community and hospital settings. Despite these favourable properties, ciprofloxacin and ofloxacin have limited potency against some clinically important organsims, such as Streptococcus pneumoniae, enterococci and anaerobes including Bacteroides fragilis and many methicillin-resistant staphylococci. In addition, occasional clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa have emerged resistant to these compounds following their introduction. In an effort to expand upon the clinical utility of the existing fluoroquinolones, several new agents of this class have been identified and are in various stages of development. Some of these newer fluoroquinolones have significantly improved antimicrobial potency against the organisms mentioned above and/or possess pharmacokinetic characterisitics in humans that suggest they could be dosed less frequently than ciprofloxacin. This review will summarise the antimicrobial and human pharmacokinetic properties of sparfloxacin, clinafloxacin, PD-131628, PD-138312, PD-140248, Q-35, AM-1155, NM394, T-3761, rufloxacin, levofloxacin, CP-99,219, OPC-17116 and DU-6859a, which appear to be among the most interesting new fluoroquinolones currently in development. An attempt will be made to distinguish the most important characterisitics of these new agents, based upon the available preclinical data and results from single dose pharmacokinetic studies in humans. The data suggest that several of these fluoroquinolones possess properties that could translate into significant clinical advantages over the currently available compounds in this class.