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Fluoroquinolones (see Table 10: 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. Fluoroquinolones are divided into 2 groups, based on antimicrobial spectrum and pharmacology:
Some newer fluoroquinolones have been withdrawn because of toxicity; they include trovafloxacin (because of severe hepatic toxicity) and gatifloxacin (because of hypoglycemia and hyperglycemia).
Pharmacology
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 the prostate, lungs, and bile.
Most fluoroquinolones are metabolized in the liver and excreted in urine, reaching high levels in urine. Moxifloxacin is eliminated primarily in bile.
Indications
Fluoroquinolones are active against the following:
Nosocomial methicillin-resistant staphylococci are usually resistant. Older fluoroquinolones have poor activity against streptococci and anaerobes. Newer fluoroquinolones have reliable activity against streptococci (including Streptococcus
pneumoniae with reduced penicillin sensitivity) and some anaerobes. As use has increased, resistance, particularly to older fluoroquinolones, is developing among Enterobacteriaceae, P.
aeruginosa, S. pneumoniae, and Neisseria sp. Nonetheless, fluoroquinolones have many clinical uses (see Table 11: Bacteria and Antibacterial Drugs: Some Clinical Uses of Fluoroquinolones).
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Table 11
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Some Clinical Uses of Fluoroquinolones
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Drug
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Use
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Comments
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Fluoroquinolones except moxifloxacin
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UTIs when Escherichia coli resistance to trimethoprim/sulfamethoxazole is > 15%
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Drugs of choice; however, increasing resistance of E. coli in some communities
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Fluoroquinolones
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Bacterial prostatitis
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—
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Salmonella bacteremia
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—
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Typhoid fever
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Usually effective
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Infectious diarrhea
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Effective against most bacterial causes (Campylobacter sp, salmonellae, shigellae, vibrios, Yersinia enterocolitica); however, increasing resistance of C. jejuni in some regions
Not used for E. coli 0157:H7
Not effective against Clostridium difficile
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Ofloxacin
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Chancroid
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3-day course
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Chlamydia trachomatis infections
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7-day course
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Newer fluoroquinolones
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Community-acquired pneumonia
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Other drugs preferred if patients have taken fluoroquinolones recently
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Legionella pneumonia
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Drugs of choice (or azithromycin )
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Ciprofloxacin
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Hospital-acquired pneumonia
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Used empirically because it is effective against Pseudomonas aeruginosa
Usually used with another antipseudomonal drug
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Long-term oral treatment of gram-negative bacillary or Staphylococcus aureus osteomyelitis
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—
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Meningococcal prophylaxis
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—
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Anthrax prophylaxis
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Used extensively during 2001 after bioterrorist attack in US
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Fluoroquinolones are no longer recommended for treatment of gonorrhea in the US because of increasing resistance.
Contraindications
Contraindications include
Fluoroquinolones have traditionally been considered to be contraindicated in children because they may cause cartilage lesions if growth plates are open. However, some experts, who challenge this view because evidence is weak, have recommended prescribing fluoroquinolones as a 2nd-line antibiotic and restricting use to a few specific situations, including P.
aeruginosa infections in patients with cystic fibrosis, prophylaxis and treatment of bacterial infections in immunocompromised patients, life-threatening multiresistant bacterial infections in neonates and infants, and Salmonella or Shigella GI tract infections.
Use
During Pregnancy and Breastfeeding
Fluoroquinolones are in pregnancy category C (animal studies show some risk, evidence in human and animal studies is inadequate, but clinical benefit sometimes exceeds risk).
Fluoroquinolones enter breast milk. Use during breastfeeding is not recommended.
Adverse
Effects
Serious adverse effects are uncommon; main concerns include the following:
Diarrhea, leukopenia, anemia, and photosensitivity are uncommon. Rash is uncommon unless gemifloxacin is used for > 1 wk and is more likely to develop in women < 40. Nephrotoxicity is rare.
Dosing
Considerations
Dose reduction, except for moxifloxacin , is required for patients with renal insufficiency. Older fluoroquinolones are normally given twice/day; newer ones and an extended-release form of ciprofloxacin are given once/day.
Ciprofloxacin raises theophylline levels, sometimes resulting in theophylline -related adverse effects.
Last full review/revision July 2009 by Matthew E. Levison, MD
Content last modified July 2009
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