Expanding Uses of Fluoroquinolones: Opportunities and Challenges

Drugs in the quinolone or related naphthyridine class have been available since the 1960s. Nalidixic acid, the first agent of the class to be used clinically, was largely limited to treatment of urinary tract infections. The mid-1980s saw the introduction of newer, more potent, fluorinated quinolones with broader spectra of activity and broader applications for treatment of bone, joint, and systemic infections and infections of the genital, gastrointestinal, and respiratory tracts [1]. Of the five fluoroquinolones introduced in the United States by 1992, ciprofloxacin and ofloxacin were most widely used because they had the greatest potency and the broadest set of approved indications [2]. Both of these agents were available in oral and intravenous formulations given twice daily and were generally well tolerated. Ciprofloxacin and ofloxacin were most active against gram-negative bacilli, less active against gram-positive cocci, and insufficiently active against anaerobic bacteria.

In the past 2 years, four new fluoroquinolones have been approved in the United States: sparfloxacin and levofloxacin in 1996 and grepafloxacin and trovafloxacin in late 1997 [3-5]. Levofloxacin is the active stereoisomer of the racemic mixture that constitutes ofloxacin; thus, levofloxacin has twofold greater activity. The newest fluoroquinolones are different from the earlier agents because they have increased activity against gram-positive bacteria and are administered once daily. Levofloxacin and trovafloxacin retain the most activity against gram-negative bacilli and have the broadest sets of indications. Trovafloxacin, in addition, is the first marketed quinolone with potent anaerobic activity. Grepafloxacin and sparfloxacin have indications limited to treatment of infections of the respiratory and genitourinary tracts.

All of these agents have been approved for treatment of community-acquired respiratory tract infections, including pneumonia and acute bacterial exacerbations of chronic bronchitis, which are most frequently caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Atypical pathogens, …