Potential interactions of the extended-spectrum fluoroquinolones with the CNS. 
The new generation fluoroquinolones -- sparfloxacin, levofloxacin, grepafloxacin and trovafloxacin -- have been designed to respond to the clinical need for extended antimicrobial cover in the face of increasing global microbial resistance.  Their main focus is in the treatment of respiratory infections, particularly those acquired in the community.  CNS adverse effects, such as dizziness and headache, are known to occur relatively commonly with some fluoroquinolones and are not, in general, well tolerated by patients.  The structural component of the fluoroquinolone molecule believed to be responsible for improved gram-positive activity is also believed to be implicated in the production of CNS adverse effects, including those arising from drug interactions with theophylline and NSAIDs.  Inhibition of brain gamma-aminobutyric acid (GABA) receptor binding appears to be a strong indicator of CNS activity, though N-methyl-D-aspartate receptor binding has also been implicated.  In accordance with the results of these predictive studies, clinical trials have found sparfloxacin, levofloxacin and grepafloxacin to be associated with a low incidence of CNS events.  Trovafloxacin has been found to be associated with a higher incidence of CNS events (particularly lightheadedness and dizziness) than the other 3 agents.  Ongoing and future clinical studies will help to define the usefulness of the predictive models, as well as reveal the full CNS adverse event profile of these and other investigational fluoroquinolones.