Quinolone therapy for infections of the central nervous system

The rationale for use of quinolones in the treatment of central nervous system (CNS) infections is reviewed. Quinolones exert potent activity in vitro against many gram-negative meningeal pathogens. Given the concentrations attained in cerebrospinal fluid (CSF), however, activity against gram-positive organisms is marginal. As a group, the quinolones enter (penetrate) the CSF better than do any other class of antimicrobial agents. The percentage penetration into CSF is remarkably similar in animal models and in humans with meningitis receiving concurrent therapy. The relative rank order for CSF penetration is as follows: enoxacin and pefloxacin (approximately 50%) greater than ciprofloxacin and ofloxacin (approximately 20%-30%). Certain quinolones have proven to be equivalent to conventional agents (e.g., third-generation cephalosporins) in the rate with which they eradicate bacterial gram-negative organisms from the CSF in experimental animal models of meningitis, but the serum concentrations have usually been higher than those achieved in humans. Despite these advantages, the concentrations in CSF remain low (e.g., ciprofloxacin, approximately 0.25-0.5 mg/L; pefloxacin, 4-8 mg/L) in humans because of the relatively low concentrations attained in serum. Thus, quinolones will continue to be most useful in the treatment of infections due to problem pathogens or to multiresistant pathogens (e.g., Pseudomonas species). Although quinolones appear to enter brain tissue readily, it is unlikely that they can be used as single agents for the treatment of brain abscess because of poor activity against anaerobes and streptococci, and no animal or human studies have been reported. A single dose of ciprofloxacin administered orally appears promising for use in eradication of the meningococcal carrier state.