Levofloxacin: New Fluoroquinolone Antibiotic
By William T. Elliott MD, FACP, and James Chan PharmD, PhD
Levofloxacin (levaquin; ortho) is a new fluoroquinolone antibiotic recently approved by the FDA. It is an extended spectrum quinolone that has improved activity against gram-positive organisms including Streptococcus pneumoniae when compared with older quinolones. Levofloxacin is the active stereoisomer of ofloxacin and is available in a parenteral preparation or as a once daily oral preparation. It is approved for a wide range of infections including community-acquired pneumonia, bronchitis, and urinary tract infections.
Levofloxacin is indicated for the treatment of adults (³ 18 years of age) with mild, moderate, and severe infections including acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, uncomplicated skin and skin structure infections, and complicated urinary tract infections including acute pyelonephritis.1 The drug is active against many gram-positive organisms including S. pneumoniae, Enterococcus faecalis, Staphylococcus aureus, and S. pyogenes. It is also active against gram-negative organisms including Enterobacter cloacae, E. coli, H. influenza, H. parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa. It also covers atypical pathogens including Chlamydia pneumoniae and Mycoplasma pneumoniae.
Levofloxacin is dosed once daily, is well absorbed orally, and penetrates well into lung tissue.1 It is active against a wide range of respiratory pathogens including atypical pathogens and S. pneumoniae resistant to penicillin.1,8 The drug is available as both an oral and parenteral form, and the oral and IV routes are interchangeable (i.e., same dose). Levofloxacin is generally well tolerated (incidence of adverse reactions, < 7%).
Levofloxacin is less active against Pseudomonas aeruginosa than ciprofloxacin.2,3 Levofloxacin is FDA approved for treating pseudomonal infections of the urinary tract only. Most common side effects include nausea, diarrhea, headache, and constipation.1 All quinolones have been associated with cartilage damage in animal studies, and they are therefore not recommended for use in children, adolescents, pregnant women, and nursing women.
Levofloxacin is supplied in a parenteral form for IV use and in 250 mg and 500 mg tablets. The recommended dose is 500 mg IV or orally qd for 7-14 days for upper or lower respiratory tract infections and uncomplicated skin and skin structure infections, and 250 mg qd for 10 days for complicated UTI or acute pyelonephritis.
Food does not affect the absorption of the drug, but it should be taken at least two hours before or two hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparation with zinc. Dosage adjustment is recommended in patients with impaired renal function (clearance £ 50 mL/min).1
Levofloxacin is the S-enatiomer of ofloxacin. In general, levofloxacin has similar activity against gram-positive organism as ofloxacin and ciprofloxacin, and it is more active than ofloxacin and slightly less active than ciprofloxacin against gram-negative organisms.2,3 It has been reported to be more active than the older quinolones against S. pneumoniae resistant to penicillin.8 Levofloxacin is active against atypical respiratory pathogens and is being heavily marketed for upper and lower respiratory infections.
Comparative trials (generally available in abstract form) suggest that levofloxacin is as effective as cefuroxime axetil, cefaclor, and amoxacillin/clavulanate in upper or lower respiratory infections.4-6 In patients with community-acquired pneumonia, IV levofloxacin with step-down to oral therapy is as effective as ceftriaxone with step-down therapy to cefuroxime axetil.7 About 22% of patients in the cephalosporin arm required the addition of erythromycin or doxycycline due to the presence of atypical respiratory pathogens. The clinical response rates (cure plus improvement) were 88-97% for levofloxacin. Microbiological eradication was reported to be 94-98%; however, a large number of patients (32-43%) were not evaluable for this end point.4,6,7
Levofloxacin and another recently approved drug, sparfloxacin, are the only quinolones approved by the FDA for respiratory tract infections including community acquired pneumonia. Currently, macrolides (erythromycin, azithromycin, or clarithromycin) are recommended for pneumonia in ambulatory, otherwise healthy adults. For older patients, an oral cephalosporin such as cefuroxime axetil may be considered.8 Levofloxacin does provide an alternative to these drugs in respiratory infections. Indiscriminate use must be avoided and the development of resistance to the quinolones considered. The wholesale cost for levofloxacin (500 mg qd for 10 days) is $58.40.
Levofloxacin is a once-a-day, broad spectrum antibiotic that may be an effective alternative for the treatment of a wide range of outpatient infections including respiratory infections and urinary tract infections. It is priced competitively with existing agents for these same indications.