QUINOLONES

I. Mechanism of action--inhibit bacterial DNA gyrase, interfering w/bacterial replication

II. Side effects

  1. Most common are nausea and diarrhea
  2. May also be associated with achilles tendon rupture, particularly in the elderly (Arch. Int. Med. 163:1801, 2003--JW)

III. Administation--don't give orally within 2h or aluminum- or magnesium-containing antacids, sucralfate, or iron-containing meds

IV. Specific agents

  1. First-generation--no gm-pos. activity; good coverage of enterobacteriaceae; poor oral absorption & tissue-penetration
    1. Nalidixic acid, oxolinic acid, etc.
  1. Second-generation--better tissue-penetration and better gm-neg (inc. pseudomonas) and slightly better gm-pos activity than 1st-gen
    1. Ciprofloxacin
      1. Active against "atypicals" (chlamydia, mycoplasma, legionella)
      2. Best fluoroquinolone for Pseudomonas
      3. May potentiate effects of warfarin, theophylline, and cyclosporine
    2. Ofloxacin (Floxin)--active against "atypicals"
    3. Norfloxacine
    4. Lomefloxacin
  1. Third-generation--spectrum similar to 2nd-gen but also active against "atypicals" and gm-positives (inc. streptococci, enterococci, and staph)
    1. Levofloxacin (Levaquin)--the active stereoisomer of Ofloxacin
    2. Grepafloxacin (Raxar)--withdrawn from US market 1999 b/c of cardiotoxicity
    3. Sparfloxacin (Zagam)
      1. Best coverage for anaerobes & mycoplasma of the 3rd-generation
      2. Causes photosensitivity
      3. Can cause prolonged QT interval
  1. Fourth-generation--spectrum similar to 3rd-gen but also active against anaerobes; may be less active against enterobacteriaceae and pseudomonas than Ciprofloxacin
    1. Trovafloxacin (Trovan)--100-200mg PO QD; 100mg PO x 1 for uncomplicated gonorrhea
  1. Also, Alatrovafloxacin (Trovan IV)--the pro-drug of trovafloxacin
  2. In addition to DNA gyrase inhibition, inhibits bacterial topoisomerase IV (involved in partitioning of bacterial DNA during cell division)
  3. Poorly concentrated in the urine so not ideal for tx of complicated urinary tract infections

Others (I'm not sure which "generation" they fall into):