The quinolones are synthetic analogs of nalidixic acid with a broad spectrum of activity against many bacteria. The mode of action of all quinolones involves inhibition of bacterial DNA synthesis by blocking the enzyme DNA gyrase.
The earlier quinolones (nalidixic acid, oxolinic acid, cinoxacin) did not achieve therapeutic systemic antibacterial levels after oral intake and thus were useful only as urinary antiseptics. The fluoroquinolone derivatives (ciprofloxacin, levofloxacin, gemifloxacin, and moxifloxacin) have more potent antibacterial activity and achieve therapeutic levels in blood and tissues. Delafloxacin, a novel fluoroquinolone, accumulates at acidic pH and may offer an advantage against intracellular infections.
With some exceptions, the spectrum of activity is similar among the available agents. In general, these medications have moderate to excellent activity against Enterobacteriaceae but are also active against other gram-negative bacteria such as Haemophilus, Neisseria, Moraxella, Brucella, Legionella, Salmonella, Shigella, Campylobacter, Yersinia, Vibrio, and Aeromonas organisms. Fluoroquinolone resistance to E coli, including ESBL-producing pathogens, has steadily increased, with many centers reporting up to 20–30% resistance. Ciprofloxacin, levofloxacin, and delafloxacin have activity against P aeruginosa, but resistance limits their utility against this pathogen. None of these agents have reliable activity against S maltophilia or B cepacia or against certain genital tract pathogens, such as Mycoplasma hominis, U urealyticum, and Chlamydia. M tuberculosis is sensitive to the quinolones, as is M fortuitum and Mycobacterium kansasii.
In general, the fluoroquinolones are less potent against gram-positive bacteria when compared with gram-negative organisms. The exception is delafloxacin, which shows enhanced activity against gram-positive organisms, including levofloxacin-nonsusceptible methicillin-resistant S aureus. Gemifloxacin, levofloxacin, and moxifloxacin also have excellent gram-positive activity, including against streptococci, pneumococci, and S aureus and S epidermidis, as well as some methicillin-resistant strains. However, the emergence of resistant strains of staphylococci, particularly with monotherapy, has limited the use of these medications in infections caused by these organisms. Use of fluoroquinolones to treat tuberculosis in South Africa has been associated with emergence of invasive disease due to levofloxacin-nonsusceptible S pneumoniae. T pallidum and Nocardia are resistant to all fluoroquinolones.
Moxifloxacin and delafloxacin demonstrate modest activity against many of the significant anaerobic pathogens, including B fragilis and mouth anaerobes, but only moxifloxacin is approved for the treatment of intra-abdominal infection. Moxifloxacin also provides the most reliable coverage of M tuberculosis.
PHARMACOKINETICS & ADMINISTRATION
After oral administration, the fluoroquinolones are well absorbed and widely distributed in body fluids and tissues and are concentrated intracellularly. Fluoroquinolones bind some heavy metals; thus, absorption is inhibited when administered concomitantly with iron, calcium, and other multivalent cations. Optimal oral bioavailability is achieved if fluoroquinolones are taken 1 hour before or 2 hours after meals. The serum half-life ranges from 4 hours (ciprofloxacin) to 12 hours (moxifloxacin). Most are eliminated via mixed renal and nonrenal pathways. As a ...