Levofloxacin and trovafloxacin: the next generation of fluoroquinolones?

ABSTRACT

The pharmacology, spectrum of activity, pharmacokinetics, clinical efficacy, and adverse effects of levofloxacin, recently approved by FDA, and trovafloxacin, currently undergoing clinical trials, are reviewed. Compared with quinolones in current use, levofloxacin is more potent against gram-negative bacteria and exhibits better antipseudomonal activity as well as greater oral bioavailability. Trovafloxacin is more potent than existing quinolones against gram-positive bacteria. Both agents exert their antibacterial effects by inhibiting bacterial DNA synthesis. Compared with other quinolones, levofloxacin and trovafloxacin both demonstrate superior activity against the Bacteroides fragilis group, Chlamydia spp., Mycoplasma pneumoniae, and Mycobacterium spp. The half-life (t1/2) of levofloxacin is nearly eight hours. Levofloxacin can therefore be administered once daily for mild to moderate infections and twice daily for more serious infections. The recommended daily dose is 500 mg. Trovafloxacin has a t1/2 of 12 hours, which allows for single daily doses, and is extensively metabolized. Levofloxacin has demonstrated clinical efficacy in the treatment of community-acquired respiratory-tract infections, genitourinary infections, skin and skin-structure infections, acute bacterial sinusitis, and infections of the head and neck. Trovafloxacin may have a role in treating skin and skin-structure or soft-tissue infections respiratory-tract infections, sexually transmitted diseases, and meningitis. Both agents are well tolerated, with central-nervous-system and gastrointestinal adverse effects reported most frequently. Concomitant administration of antacids or compounds containing meal cations decreases absorption of these quinolones. Levofloxacin and trovafloxacin have favorable antimicrobial and pharmacokinetic profiles, offering the advantages of once-daily doses as well as superior potency and spectrum of activity compared with currently available quinolones.