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The fluoroquinolones (see Table 9: Bacteria and Antibacterial Drugs: Fluoroquinolones ) exhibit concentration-dependent bactericidal activity by inhibiting the activity of DNA gyrase and topoisomerase, enzymes essential for bacterial DNA replication. The fluoroquinolones are divided into 2 groups, based on antimicrobial spectrum and pharmacology: the older group includes ciprofloxacin , norfloxacin , and ofloxacin , and the newer group, gatifloxacin , gemifloxacin , levofloxacin , moxifloxacin , and trovafloxacin.
Pharmacology:
Ciprofloxacin , gatifloxacin , levofloxacin , moxifloxacin , ofloxacin , and trovafloxacin can be administered orally and parenterally; gemifloxacin and norfloxacin are available only orally. Several fluoroquinolones are also available as otic and ophthalmic preparations. Oral absorption is diminished by coadministration of cations (aluminum, Mg, Ca, zinc, and iron preparations). After oral and parenteral administration, fluoroquinolones are widely distributed in most extracellular and intracellular fluids and are concentrated in prostate, lung, and bile. Most are metabolized in the liver and excreted in urine, reaching high levels in urine. Moxifloxacin is primarily eliminated in bile. Dosing reduction is required in renal insufficiency, except for moxifloxacin . Older fluoroquinolones are normally given twice/day; newer ones and an extended-release form of ciprofloxacin are given once/day.
Indications:
The fluoroquinolones are active against Neisseria
, Haemophilus influenzae
, Moraxella catarrhalis
, Mycoplasma
, Chlamydia and Chlamydophila
, Legionella
, Enterobacteriaceae, and, particularly ciprofloxacin , Pseudomonas aeruginosa. The fluoroquinolones are also active against Mycobacterium
tuberculosis
, some atypical mycobacteria, and methicillin-sensitive staphylococci, but nosocomial methicillin-resistant staphylococci are usually resistant. The older fluoroquinolones have poor activity against streptococci and anaerobes. Newer fluoroquinolones have reliable activity against streptococci (including Streptococcus pneumoniae with reduced penicillinsensitivity) and some anaerobes. As use has increased, resistance is developing among Enterobacteriaceae, P. aeruginosa
, S. pneumoniae
, and Neisseria
, particularly among older fluoroquinolones.
Fluoroquinolones (except moxifloxacin ) are the empiric drugs of choice for UTIs where Escherichia coli resistance to trimethoprim-sulfamethoxazole is > 15%. They are effective in bacterial prostatitis, Salmonella bacteremia, and usually typhoid fever. Fluoroquinolones have excellent activity against most bacterial causes of infectious diarrhea (Salmonella sp, Campylobacter sp, Shigella sp, Vibrio sp, and Yersinia enterocolitica), except that caused by Clostridium difficile. A 3-day course of ofloxacin is effective for chancroid, and a 7-day course of ofloxacin is recommended for infections caused by Chlamydia trachomatis. The newer fluoroquinolones are used often for community-acquired pneumonia; however, another regimen should be used for patients with recent fluoroquinolone use. The newer fluoroquinolones (and azithromycin ) are drugs of choice for Legionella pneumonia. Ciprofloxacin , because of its superior activity against P.
aeruginosa, is used empirically for hospital-acquired pneumonia, usually with another antipseudomonal drug. Ciprofloxacin is used for long-term oral treatment of gram-negative bacillary or Staphylococcus aureus osteomyelitis and for meningococcal prophylaxis and was used extensively for anthrax prophylaxis in the 2001 bioterrorism event in the US.
Toxicity:
Serious adverse reactions are uncommon. About 5% of patients experience upper GI adverse effects due to direct GI irritation and CNS effects. Diarrhea, leukopenia, anemia, and photosensitivity are uncommon. Rash is uncommon except if gemifloxacin is used for > 1 wk, especially in women < 40 yr of age. Fluoroquinolones predispose to tendinopathy, including rupture of the Achilles tendon, even after short-term use. Nephrotoxicity is rare. CNS effects occur in < 5%, including mild headache, drowsiness, insomnia, dizziness, and mood alteration. Trovafloxacin has the highest rate of CNS adverse events, most often dizziness, lightheadness, or vertigo. Seizures are rare, but these drugs should be avoided in patients with CNS disorders. NSAIDs may enhance the CNS stimulatory effects of the fluoroquinolones. Fluoroquinolones are contraindicated in children and may cause cartilage lesions if growth plates are open. The safety of fluoroquinolones in pregnancy has not been established. Ciprofloxacin raises theophylline levels, which may result in theophylline -related adverse effects. Fluoroquinolones can prolong the QT interval, potentially leading to ventricular arrhythmias and sudden cardiac death. The risk of arrhythmias may be reduced by avoiding their use in patients with known QT interval prolongation; in those with uncorrected hypokalemia, hypomagnesemia, or significant bradycardia; and in those receiving concomitant therapy with agents known to increase the QT interval or to cause bradycardia ( metoclopramide , cisapride , erythromycin , clarithromycin , classes Ia and III antiarrhythmics, and tricyclic antidepressants). In rare cases, trovafloxacin causes severe hepatotoxicity, especially if it is used for > 2 wk; thus, trovafloxacin is rarely used.
Last full review/revision November 2005
Content last modified November 2005
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