versus Gram-positive species is useful for differentiating these agents. Norfloxacin, which is no longer available in the USA, is the least active of the fluoroquinolones against both Gram-negative and Gram-positive organisms, with minimum inhibitory concentrations (MICs) fourfold to eightfold higher than those of ciprofloxacin. Ciprofloxacin, enoxacin, lomefloxacin, levofloxacin, ofloxacin, and pefloxacin comprise a second group of similar agents possessing excellent Gram-negative activity and moderate to good activity against Gram-positive bacteria. Ciprofloxacin and levofloxacin are the two agents from this group that are used systemically in the USA. MICs for Gram-negative cocci and bacilli, including Enterobacter sp, P aeruginosa, Neisseria meningitidis, Haemophilus sp, and Campylobacter jejuni, are 1–2 mcg/mL and often less. Methicillin-susceptible strains of S aureus are generally susceptible to these fluoroquinolones, but methicillin-resistant strains of staphylococci are often resistant. When treating staphylococcal infections, fluoroquinolones are typically used in combination with a second active agent, such as rifampin, to prevent emergence of resistance while on therapy. Enterococci tend to be less susceptible than staphylococci, limiting the efficacy of fluoroquinolones in infections caused by these organisms. Ciprofloxacin is the most active agent of this group against Gram-negative organisms, particularly P aeruginosa. Levofloxacin, the l-isomer of ofloxacin, has superior activity against Gram-positive organisms, especially Streptococcus pneumoniae.
Gatifloxacin, gemifloxacin, and moxifloxacin make up a third group of fluoroquinolones with improved activity against Gram-positive organisms, particularly S pneumoniae and some staphylococci. Gemifloxacin is active in vitro against ciprofloxacin-resistant strains of S pneumoniae, but in vivo efficacy is unproven. Although MICs of these agents for staphylococci are lower than those of ciprofloxacin (and the other compounds mentioned in the paragraph above), it is not known whether the enhanced activity is sufficient to permit use of these agents for treatment of infections caused by
TABLE 46–1 Pharmacokinetic properties of some fluoroquinolones.
Norfloxacin 3.5–5 80 1.5 400 twice daily Renal Ofloxacin 5–7 95 2.9 400 twice daily Renal ciprofloxacin-resistant strains. In general, none of these agents is as active as ciprofloxacin against Gram-negative organisms. Fluoroquinolones also are active against agents of atypical pneumonia (eg, mycoplasmas and chlamydiae) and against intracellular pathogens such as Legionella and some mycobacteria, including Mycobacterium tuberculosis and Mycobacterium avium complex. Moxifloxacin has modest activity against anaerobic bacteria but lacks appreciable activity against P aeruginosa. Because of toxicity when systemically administered, gatifloxacin is available only as an ophthalmic solution in the USA.