After their appearance, for more than 20-years quinolones offered little improvement over nalidixic acid. Later, fluoroquinolones a new family of analogues featuring a fluorine atom at position 6, were discovered and exhibited greatly improved properties. These compounds are much more active than earlier derivatives against enterobacteria, P. aeruginosa, and many Gram-positive cocci, though the activity is somewhat reduced in acidic conditions and in the presence of divalent cations such as magnesium, which make a complex coordinating the two carbonyl groups at position 3 and 4. The spectrum also includes certain difficult organisms such as chlamydiae, legionellae, and some mycobacteria. Similar compounds, including enrofloxacin, danofloxacin, and sarafloxacin, have been introduced into veterinary practice and there has been considerable debate about the impact this may have had on the development of resistance.
The success of the first fluoroquinolones stimulated an intensive search for new derivatives with improved properties and this has yielded several new agents that have reached the market, or an advanced stage of development. These compounds are characterized by superior activity against Gram-positive cocci, including S. aureus and Streptococcus pneumoniae as well as chlamydiae and mycoplasmas; clinafloxacin, gatifloxacin, moxifloxacin, and trovafloxacin have sufficient activity against anaerobes of the Bacteroides fragilis group. They are not reliably active against Ps. aeruginosa.
Fluoroquinolones are usually administered orally, although some, including ciprofloxacin, ofloxacin, levofloxacin (the L-isomer of ofloxacin), and trovafloxacin (in the form of its prodrug, alatrofloxacin), can be given by injection. The therapeutic dosages produce relatively low plasma concentrations, but the compounds are well distributed in tissues and concentrate within mammalian cells. The major route of excretion is usually renal, in the form of unchanged compound or glucuronide and other metabolites, some of which retain antibacterial activity. Some fluoroquinolones, like rufloxacin, sparfloxacin, moxifloxacin, and trovafloxacin, show long terminal half-lives; these compounds are partly excreted by the biliary route which could explain the long half-life.
Among fluoroquinolones, norfloxacin, enoxacin, and lomefloxacin are used in the treatment of urinary tract infection, though they may also have wider uses, for example in gonococcal and gastrointestinal infections. Other fluoroquinolones are used for systemic infection. Ciprofloxacin is the most widely used; among other indications, it is the drug of choice for typhoid fever and other serious enteric diseases. The ease of administration of fluoroquinolones makes them attractive candidates for empiric therapy in hospital and domiciliary practice.
This generation of quinolones includes: Ciprofloxacin,
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