Moxifloxacin (Bay 12-8039): a new methoxy quinolone antibacterial

Moxifloxacin (Bay 12-8039) is a new 8 methoxy quinolone antibacterial. The MIC90 values are < or = 0.25 mg/l for Streptococcus pneumoniae (irrespective of penicillin susceptibility), Haemophilus influenzae (beta-lactamase positive or negative), Morexella catarrhalis, Bordetella pertussis, Legionella sp., Mycoplasma pneumoniae, Clamydia pneumoniae, Mycobacterium tuberculosis, methicillin-sensitive Staphylococcus aureus, beta-haemolytic streptococci (macrolide-sensitive or -resistant), Listeria sp., most Enterobacteriaceae, Salmonella sp., Shigella sp., Neisseria gonorrhoeae, N. menigitidis, Pasteurella spp., Vibrio spp. and Yersinia enterocolitica. For Mycobacterium intracellularae, methicillin-resistant S. aureus (MRSA), ciprofloxacin-resistant S. aureus, Citrobacter freundii, Providencia sp., Serratia sp., P. aeruginosa and other non-fermentive Gram-negative rods, MIC90s are in the range 0.5-4 mg/l. For anaerobic bacteria species, MIC90s are also in the range 0.25-4 mg/l. Moxifloxacin is bactericidal at concentrations 2- to 4-fold higher than the MIC and is rapidly bactericidal against most common pathogen groups at concentrations achieved in serum with a 400 mg dose that is between 0.5-4 mg/l. There is a post-antibiotic effect against Gram-positive and -negative bacteria. Resistant mutants are at present difficult to select in the laboratory but in general, moxifloxacin has poorer activity against strains resistant to ciprofloxacin compared to those which are susceptible. Animal and laboratory pharmacodynamic models indicate that the MIC and area under the serum concentration time curve predict outcome. Various animal models mainly of respiratory tract infection indicate equivalent or superior results compared to existing or other developmental agents. Human pharmacokinetics in healthy volunteers indicate linear pharmacokinetics over the dose range 50-800 mg/day. A single dose of 400 mg produces a maximum serum concentration of 2.5-4.5 mg/l, half-life of 11-15 h, AUC of 25-40 mg x h/l and volume of distribution of 2.5-3.5 L/kg. Protein binding is about 50% and two metabolites have been identified (M-1 and M-2). Bioavailability is > 85% and a minority of clearance is via the kidneys. No dose modification is required in renal impairment. Extra vascular penetration, where studied, is comparable to that of other quinolones. At present undergoing clinical trials, with a focus on respiratory tract infection, it is likely that moxifloxacin will provide effective therapy for pathogens with MICs of < or = 0.25-0.5 mg/l. The safety profile in a large number of human subjects is awaited.