Use of fluoroquinolones in central nervous system infections

Newer fluoroquinolones have excellent activity versus Streptococcus pneumoniae, and retain activity versus Neisseria meningitidis, Haemophilus influenzae, and Listeria monocytogenes, the most common causative organisms in bacterial meningitis. The newer fluoroquinolones, including levofloxacin, trovafloxacin, gatifloxacin, moxifloxacin, and gemifloxacin are lipophilic and penetrate into the CNS well enough to exceed typical bacterial MICs. Clinical advantages of fluoroquinolones in the treatment of meningitis include: (1) good CSF penetration regardless of inflammation, (2) excellent oral bioavailability, (3) easy administration, with the potential for QD-BID dosing, (4) delayed endotoxin release, and (5) activity unaffected by fever, high titers, and stationary growth. Disadvantages include: (1) resistance potential, (2) possible arthropathy in children, (3) CNS stimulation, (4) lack of clinical investigations, and (5) potential drug-drug interactions. Preliminary data from in vitro and animal studies supporting fluoroquinolone use in meningitis suggest T > MBC, AUC/MBC and Cp-max/MBC all predict activity. However, optimal pharmacodynamic outcome parameters for fluoroquinolone activity in meningitis have not been determined and validated. Comparative, controlled clinical efficacy trials in patients with meningitis will be necessary to determine the place of fluoroquinolones in the therapy of meningitis.